Pathoma_Husain

Pathoma_Husain. A. Most common cause of nephrotic syndrome in Hispanics and African Americans B. Usually idiopathic; may be associated with HIV, heroin use, and sickle cell disease C. Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis on H&E stain (Fig. 12.8) D. Effacement of foot processes on EM E. No immune complex deposits; negative IF F. Poor response to steroids; progresses to chronic renal failure IV. A. Most common cause of nephrotic syndrome in Caucasian adults B. Usually idiopathic; may be associated with hepatitis B or C, solid tumors, SLE, or drugs (e.g., NSAIDs and penicillamine) C. Thick glomerular basement membrane on H&E (Fig. 12.9A) D. Due to immune complex deposition (granular IF, Fig. 12.9B); subepithelial deposits with 'spike and dome' appearance on EM (Fig. 12.9C) E. Poor response to steroids; progresses to chronic renal failure V. A. Thick glomerular basement membrane on H&E, often with 'tram-track' appearance


Pathoma_Husain

Pathoma_Husain. E. Poor response to steroids; progresses to chronic renal failure V. A. Thick glomerular basement membrane on H&E, often with 'tram-track' appearance B. Due to immune complex deposition (granular IF) C. Divided into two types based on location of deposits 1. Type I-subendothelial (Fig. 12.10); associated with HBV and HCV 2. Type II (dense deposit disease)-intramembranous; associated with C3 nephritic factor (autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation, and low levels of circulating C3) D. Poor response to steroids; progresses to chronic renal failure VI. DIABETES MELLITUS A. High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting in hyaline arteriolosclerosis. Fig. 12.7 Minimal change disease. A, Normal glomerulus. B, Effacement of foot processes on EM. Fig. 12.8 Focal segmental glomerulosclerosis. (Courtesy ofTony Chang, MD)


Pathoma_Husain

Pathoma_Husain. Fig. 12.7 Minimal change disease. A, Normal glomerulus. B, Effacement of foot processes on EM. Fig. 12.8 Focal segmental glomerulosclerosis. (Courtesy ofTony Chang, MD) B. Glomerular efferent arteriole is more affected than the afferent arteriole, leading to high glomerular filtration pressure. 1. Hyperfiltration injury leads to microalbuminuria. C. Eventually progresses to nephrotic syndrome 1. Characterized by sclerosis of the mesangium with formation of KimmelstielWilson nodules (Fig. 12.11) D. ACE inhibitors slow progression ofhyperfiltration-induced damage. VII. SYSTEMIC AMYLOIDOSIS A. Kidney is the most commonly involved organ in systemic amyloidosis. B. Amyloid deposits in the mesangium, resulting in nephrotic syndrome. C. Characterized by apple-green birefringence under polarized light after staining with Congo red I. BASIC PRINCIPLES A. Glomerular disorders characterized by glomerular inflammation and bleeding 1. Limited proteinuria (< 3.5 g/day) 2. 3.


Pathoma_Husain

Pathoma_Husain. I. BASIC PRINCIPLES A. Glomerular disorders characterized by glomerular inflammation and bleeding 1. Limited proteinuria (< 3.5 g/day) 2. 3. Salt retention with periorbital edema and hypertension 4. B. Biopsy reveals hypercellular, inflamed glomeruli (Fig. 12.12). Fig. 12.9 Membranous nephropathy. A, Thick glomerular basement membranes. B, Granular IF. C, Subepithelial deposits with 'spike and dome' appearance. (Courtesy ofTony Chang, MD) 1. Immune-complex deposition activates complement; CSa attracts neutrophils, which mediate damage. A. Nephritic syndrome that arises after group A 0-hemolytic streptococcal infection of the skin (impetigo) or pharynx 1. Occurs with nephritogenic strains 2. May occur after infection with nonstreptococcal organisms as well B. Presents 2-3 weeks after infection as hematuria (cola-colored urine), oliguria, hypertension, and periorbital edema 1. Usually seen in children, but may occur in adults C. Hypercellular, inflamed glomeruli on H&E


Pathoma_Husain

Pathoma_Husain. C. Hypercellular, inflamed glomeruli on H&E D. Mediated by immune complex deposition (granular IF); subepithelial 'humps' on EM (Fig. 12.13) E. Treatment is supportive. 1. Children rarely (1%) progress to renal failure. 2. Some adults (25%) develop rapidly progressive glomerulonephritis (RPGN). III. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS A. Nephritic syndrome that progresses to renal failure in weeks to months Table 12.1: lmmunotluorescence Findings in Rapidly Progressive Glomerulonephritis IMMUNOFI.UORESCENCE > . . • . ... l'A'ITERN I ISl:ASI·. COMMl:N IS antibody, Fig. 12.15) presents as hematuria and hemoptysis, classically in young, adult males Diffuse proliferative glomerulonephritis is Granular (immune complex PSGN (most common) or diffuse proliferative due to diffuse antigen-antibody complex deposition) glomerulonephritis deposition, usually sub-endothelial; most common type of renal disease in SLE


Pathoma_Husain

Pathoma_Husain. Wegener granulomatosis is associated with c-ANCA; microscopic polyangiitis and Wegener granulomatosis, microscopic Churg-Strauss are associated with p-ANCA. polyangiitis, and Churg-Strauss syndrome Granulomatous inflammation, eosinophilia, and asthma distinguish Churg-Strauss from microscopic polyangiitis. Fig. 12.13 Subepithelial 'humps,' PSGN. (Courtesy Fig. 12.14 Crescent formation, rapidly ofTony Chang, MD) progressive glomerulonephritis. B. Characterized by crescents in Bowman space (of glomeruli) on H&E stain; crescents are comprised of fibrin and macrophages (Fig. 12.14). C. Clinical picture and IF help resolve etiology (Table 12.1). IV. A. IgA immune complex deposition in mesangium of glomeruli; most common nephropathy worldwide B. Presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following mucosa! infections (e.g., gastroenteritis) 1. IgA production is increased during infection.


Pathoma_Husain

Pathoma_Husain. B. Presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following mucosa! infections (e.g., gastroenteritis) 1. IgA production is increased during infection. C. IgA immune complex deposition in the mesangium is seen on IF (Fig. 12.16). D. May slowly progress to renal failure V. A. Inherited defect in type IV collagen; most commonly X-linked B. Results in thinning and splitting of the glomerular basement membrane C. Presents as isolated hematuria, sensory hearing loss, and ocular disturbances I. BASIC PRINCIPLES A. Infection of urethra, bladder, or kidney B. Most commonly arises due to ascending infection; increased incidence in females C. Risk factors include sexual intercourse, urinary stasis, and catheters. II. CYSTITIS A. Infection of the bladder B. Presents as dysuria, urinary frequency, urgency, and suprapubic pain; systemic signs (e.g., fever) are usually absent. C. Laboratory findings 1.


Pathoma_Husain

Pathoma_Husain. II. CYSTITIS A. Infection of the bladder B. Presents as dysuria, urinary frequency, urgency, and suprapubic pain; systemic signs (e.g., fever) are usually absent. C. Laboratory findings 1. Urinalysis-cloudy urine with > 10 WBCs/high power field (hpf) 2. Dipstick-Positive leukocyte esterase (due to pyuria) and nitrites (bacteria convert nitrates to nitrites) 3. Culture-greater than 100,000 colony forming units (gold standard) D. Etiology 1. E coli (80%) 2. Staphylococcus saprophyticus-increased incidence in young, sexually active women (but E coli is still more common in this population) 3. Klebsiella pneumoniae 4. Proteus mirabilis-alkaline urine with ammonia scent Fig. 12.15 Linear IF, Goodpasture syndrome. Fig. 12.16 lgA nephropathy. (Courtesy ofTony (Courtesy ofTony Chang, MD) Chang, MD) 5. Enterococcus faecalis E. Sterile pyuria is the presence of pyuria (> 10 WBCs/hpf and leukocyte esterase) with a negative urine culture.


Pathoma_Husain

Pathoma_Husain. E. Sterile pyuria is the presence of pyuria (> 10 WBCs/hpf and leukocyte esterase) with a negative urine culture. 1. Suggests urethritis due to Chlamydia trachomatis or Neisseria gonorrhoeae (dominant presenting sign of urethritis is dysuria) III. PYELONEPHRITIS A. Infection of the kidney 1. Usually due to ascending infection; increased risk with vesicoureteral reflux B. Presents with fever, flank pain, WBC casts, and leukocytosis in addition to symptoms of cystitis C. Most common pathogens are 1. E coli (90%) 2. 3. IV. CHRONIC PYELONEPHRITIS A. Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis B. Due to vesicoureteral reflux (children) or obstruction (e.g., BPH or cervical carcinoma) C. Leads to cortical scarring with blunted calyces; scarring at upper and lower poles is characteristic of vesicoureteral reflux.


Pathoma_Husain

Pathoma_Husain. C. Leads to cortical scarring with blunted calyces; scarring at upper and lower poles is characteristic of vesicoureteral reflux. D. Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles ('thyroidization' of the kidney, Fig. 12.17); waxy casts may be seen in urine. I. BASIC PRINCIPLES A. Precipitation of a urinary solute as a stone (Table 12.2) B. Risk factors include high concentration of solute in the urinary filtrate and low urine volume. C. Presents as colicky pain with hematuria and unilateral flank tenderness 1. Stone is usually passed within hours; if not, surgical intervention may be required. I. BASIC PRINCIPLES A. End-stage kidney failure 1. May result from glomerular, tubular, inflammatory, or vascular insults 2. Most common causes are diabetes mellitus, hypertension, and glomerular disease. B. Clinical features 1.


Pathoma_Husain

Pathoma_Husain. May result from glomerular, tubular, inflammatory, or vascular insults 2. Most common causes are diabetes mellitus, hypertension, and glomerular disease. B. Clinical features 1. Uremia-Increased nitrogenous waste products in blood (azotemia) result in nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, and deposition of urea crystals in skin. 2. Salt and water retention with resultant hypertension 3. Hyperkalemia with metabolic acidosis 4. Anemia due to decreased erythropoietin production by renal peritubular interstitial cells 5. Hypocalcemia due to decreased !-alpha-hydroxylation ofvitamin D by proximal renal tubule cells and hyperphosphatemia 6. Renal osteodystrophy due to secondary hyperparathyroidism, osteomalacia, and osteoporosis C. Treatment involves dialysis or renal transplant. 1. Cysts often develop within shrunken end-stage kidneys during dialysis, increasing risk for renal cell carcinoma. I. ANGIOMYOLIPOMA


Pathoma_Husain

Pathoma_Husain. C. Treatment involves dialysis or renal transplant. 1. Cysts often develop within shrunken end-stage kidneys during dialysis, increasing risk for renal cell carcinoma. I. ANGIOMYOLIPOMA A. Hamartoma comprised of blood vessels, smooth muscle, and adipose tissue B. Increased frequency in tuberous sclerosis II. RENAL CELL CARCINOMA A. Malignant epithelial tumor arising from kidney tubules Fig. 12.17 'Thyroidization' of kidney, chronic Fig. 12.18 Ammonium magnesium phosphate pyelonephritis. stone. (Courtesy of webpathology.com) B. Presents with classic triad of hematuria, palpable mass, and flank pain 1. All three symptoms rarely occur together; hematuria is the most common symptom. 2. Fever, weight loss, or paraneoplastic syndrome (e.g., EPO, renin, PTHrP, or ACTH) may also be present. 3. Rarely may present with left-sided varicocele i. Involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein leading to varicocele.


Pathoma_Husain

Pathoma_Husain. 3. Rarely may present with left-sided varicocele i. Involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein leading to varicocele. 11. Right spermatic vein drains directly into the IVC; hence, right-sided varicocele is not seen. C. Gross exam reveals a yellow mass (Fig. 12.19A); microscopically, the most common variant exhibits clear cytoplasm (clear cell type, Fig. 12.19B). D. Pathogenesis involves loss of VHL (3p) tumor suppressor gene, which leads to increased IGF-1 (promotes growth) and increased HIF transcription factor (increases VEGF and PDGF). E. Tumors may be hereditary or sporadic. 1. Sporadic tumors classically arise in adult males (average age is 60 years) as a single tumor in the upper pole of the kidney; major risk factor for sporadic tumors is cigarette smoke. 2. Hereditary tumors arise in younger adults and are often bilateral.


Pathoma_Husain

Pathoma_Husain. 2. Hereditary tumors arise in younger adults and are often bilateral. i. Von Hippel-Lindau disease is an autosomal dominant disorder associated with inactivation of the VHL gene leading to increased risk for hemangioblastoma of the cerebellum and renal cell carcinoma. F. Staging 1. T-based on size and involvement of the renal vein (occurs commonly and increases risk of hematogenous spread to the lungs and bone) 2. N-spread to retroperitoneal lymph nodes III. WILMS TUMOR A. Malignant kidney tumor comprised ofblastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells (Fig. 12.20) 1. Most common malignant renal tumor in children; average age is 3 years. B. Presents as a large, unilateral flank mass with hematuria and hypertension (due to renin secretion) C. Most cases (90%) are sporadic; syndromic tumors may be seen with 1.


Pathoma_Husain

Pathoma_Husain. B. Presents as a large, unilateral flank mass with hematuria and hypertension (due to renin secretion) C. Most cases (90%) are sporadic; syndromic tumors may be seen with 1. WAGR syndrome-Wilms tumor, Aniridia, Genital abnormalities, and mental and motor Retardation; associated with deletion of WTl tumor suppressor gene (located at llpl3) 2. Denys-Drash syndrome-Wilms tumor, progressive renal (glomerular) disease, and male pseudohermaphroditism; associated with mutations of WTl Fig. 12.19 Renal cell carcinoma. A, Gross appearance. B, Microscopic appeara nce. Fig, 12,20 Wl lms tumor. 3. Beckwith-Wiedemann syndrome-Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, and organomegaly (including tongue); associated with mutations in WT2 gene cluster (imprinted genes at llplS.5), particularly IGF-2 I. UROTHELIAL (TRANSITIONAL CELL) CARCINOMA


Pathoma_Husain

Pathoma_Husain. I. UROTHELIAL (TRANSITIONAL CELL) CARCINOMA A. Malignant tumor arising from the urothelial lining of the renal pelvis, ureter, bladder, or urethra 1. Most common type of lower urinary tract cancer; usually arises in the bladder B. Major risk factor is cigarette smoke; additional risk factors are naphthylamine, azo dyes, and long-term cyclophosphamide or phenacetin use. C. Generally seen in older adults; classically presents with painless hematuria D. Arises via two distinct pathways (Fig. 12.21) 1. Flat-develops as a high-grade flat tumor and then invades; associated with early p53 mutations 2. Papillary-develops as a low-grade papillary tumor that progresses to a highgrade papillary tumor and then invades; not associated with early p53 mutations E. Tumors are often multifocal and recur ("field defect"). II. SQUAMOUS CELL CARCINOMA A. Malignant proliferation of squamous cells, usually involving the bladder


Pathoma_Husain

Pathoma_Husain. E. Tumors are often multifocal and recur ("field defect"). II. SQUAMOUS CELL CARCINOMA A. Malignant proliferation of squamous cells, usually involving the bladder B. Arises in a background ofsquamous metaplasia (normal bladder surface is not lined by squamous epithelium) C. Risk factors include chronic cystitis (older woman), Schistosoma haematobium infection (Egyptian male), and long-standing nephrolithiasis. III. ADENOCARCINOMA A. Malignant proliferation of glands, usually involving bladder B. Arises from a urachal remnant (tumor develops at the dome of the bladder), cystitis glandularis, or exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls) Fig. 12.21 Urothelial carcinoma. A, Flat. B, Papi llary. I. BASIC PRINCIPLES A. Anatomically includes the skin and mucosa of the female genitalia external to the hymen (labia majora, labia minora, mons pubis, and vestibule) B. Lined by squamous epithelium II. BARTHOLIN CYST


Pathoma_Husain

Pathoma_Husain. B. Lined by squamous epithelium II. BARTHOLIN CYST A. Cystic dilation of the Bartholin gland 1. One Bartholin gland is present on each side of the vaginal canal and produces mucus-like fluid that drains via ducts into the lower vestibule. B. Arises due to inflammation and obstruction of gland 1. Usually occurs in women of reproductive age C. Presents as a unilateral, painful cystic lesion at the lower vestibule adjacent to the vaginal canal III. CONDYLOMA A. Warty neoplasm of vulvar skin, often large B. Most commonly due to HPV types 6 or 11 (condyloma acuminatum, Fig. 13.lA); secondary syphilis (condyloma latum) is a less common cause. Both are sexually transmitted. C. Histologically, HPV-associated condylomas are characterized by koilocytes (hallmark ofHPV-infected cells, Fig. 13.lB). D. Condylomas rarely progress to carcinoma (6 and 11 are low-risk HPV types). IV. A. Characterized by thinning of the epidermis and fibrosis (sclerosis) of the dermis


Pathoma_Husain

Pathoma_Husain. D. Condylomas rarely progress to carcinoma (6 and 11 are low-risk HPV types). IV. A. Characterized by thinning of the epidermis and fibrosis (sclerosis) of the dermis B. Presents as a white patch (leukoplakia) with parchment-like vulvar skin C. Most commonly seen in postmenopausal women; possible autoimmune etiology D. Benign, but associated with a slightly increased risk for squamous cell carcinoma V. A. Characterized by hyperplasia of the vulvar squamous epithelium B. Presents as leukoplakia with thick, leathery vulvar skin C. Associated with chronic irritation and scratching D. Benign; no increased risk of squamous cell carcinoma VI. VULVAR CARCINOMA A. Carcinoma arising from squamous epithelium lining the vulva B. Relatively rare, accounting for only a small percentage of female genital cancers C. Presents as leukoplakia; biopsy may be required to distinguish carcinoma from other causes ofleukoplakia. D. Etiology may be HPV related or non-HPV related.


Pathoma_Husain

Pathoma_Husain. C. Presents as leukoplakia; biopsy may be required to distinguish carcinoma from other causes ofleukoplakia. D. Etiology may be HPV related or non-HPV related. E. HPV-related vulvar carcinoma is due to high-risk HPV types 16 and 18. pathoma.com 1. Risk factors are related to HPV exposure and include multiple partners and early first age of intercourse; generally occurs in women of reproductive age 2. Arises from vulvar intraepithelial neoplasia (VIN), a dysplastic precursor lesion characterized by koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity F. Non-HPV related vulvar carcinoma arises, most often, from long-standing lichen sclerosis. 1. Chronic inflammation and irritation eventually lead to carcinoma. 2. Generally seen in elderly women (average age is > 70 years) VII. EXTRAMAMMARY PAGET DISEASE A. Characterized by malignant epithelial cells in the epidermis of the vulva (Fig. 13.2A)


Pathoma_Husain

Pathoma_Husain. 2. Generally seen in elderly women (average age is > 70 years) VII. EXTRAMAMMARY PAGET DISEASE A. Characterized by malignant epithelial cells in the epidermis of the vulva (Fig. 13.2A) B. Presents as erythematous, pruritic, ulcerated vulvar skin C. Represents carcinoma in situ, usually with no underlying carcinoma 1. Paget disease of the nipple is also characterized by malignant epithelial cells in the epidermis of the nipple, but it is almost always associated with an underlying carcinoma. D. Must be distinguished from melanoma, which rarely can occur on the vulva 1. Paget cells are PAS+, keratin+, and S-100-. 2. Melanoma is PAS-, keratin-, and S-100+. I. BASIC PRINCIPLES A. Canal leading to the cervix B. Mucosa is lined by non-keratinizing squamous epithelium II. ADENOSIS


Pathoma_Husain

Pathoma_Husain. 2. Melanoma is PAS-, keratin-, and S-100+. I. BASIC PRINCIPLES A. Canal leading to the cervix B. Mucosa is lined by non-keratinizing squamous epithelium II. ADENOSIS A. Focal persistence of columnar epithelium in the upper vagina (Fig. 13.2B) 1. During development, squamous epithelium from the lower 1/3 of the vagina (derived from the urogenital sinus) grows upward to replace the columnar epithelium lining of the upper 2/3 of the vagina (derived from the Miillerian ducts). B. Increased incidence in females who were exposed to diethylstilbestrol (DES) in utero Ill. CLEAR CELL ADENOCARCINOMA A. Malignant proliferation of glands with clear cytoplasm B. Rare, but feared, complication of DES-associated vaginal adenosis Fig. 13.1 Condyloma acuminata. A, Microscopic appearance. B, Koi iocytic change. Fig. 13.2A Extramammary Paget disease of the vulva. (Courtesy of webpathology.com)


Pathoma_Husain

Pathoma_Husain. Fig. 13.1 Condyloma acuminata. A, Microscopic appearance. B, Koi iocytic change. Fig. 13.2A Extramammary Paget disease of the vulva. (Courtesy of webpathology.com) C. Discovery of this complication (along with other DES-induced abnormalities of the gynecologic tract such as abnormal shape of the uterus) led to cessation of DES usage. IV. A. Malignant mesenchymal proliferation of immature skeletal muscle; rare B. Presents as bleeding and a grape-like mass protruding from the vagina or penis of a child (usually< 5 yrs of age); also known as sarcoma botryoides (Fig. 13.3) C. Rhabdomyoblast, the characteristic cell, exhibits cytoplasmic cross-striations and positive immunohistochemical staining for desmin and myogenin. V. A. Carcinoma arising from squamous epithelium lining the vaginal mucosa B. Usually related to high-risk HPV C. Precursor lesion is vaginal intraepithelial neoplasia (VAIN).


Pathoma_Husain

Pathoma_Husain. V. A. Carcinoma arising from squamous epithelium lining the vaginal mucosa B. Usually related to high-risk HPV C. Precursor lesion is vaginal intraepithelial neoplasia (VAIN). D. When spread to regional lymph nodes occurs, cancer from the lower 1/3 ofvagina goes to inguinal nodes, and cancer from the upper 2/3 goes to regional iliac nodes. I. BASIC PRINCIPLES A. Anatomically, comprises the "neck" of the uterus B. Divided into the exocervix (visible on vaginal exam) and endocervix 1. Exocervix is lined by nonkeratinizing squamous epithelium. 2. Endocervix is lined by a single layer of columnar cells. 3. Junction between the exocervix and endocervix is called the transformation zone (Fig. 13.4A). II. HPV A. Sexually transmitted DNA virus that infects the lower genital tract, especially the cervix in the transformation zone


Pathoma_Husain

Pathoma_Husain. II. HPV A. Sexually transmitted DNA virus that infects the lower genital tract, especially the cervix in the transformation zone B. Infection is usually eradicated by acute inflammation; persistent infection leads to an increased risk for cervical dysplasia (cervical intraepithelial neoplasia, CIN). C. Risk of CIN depends on HPV type, which is determined by DNA sequencing. 1. High-risk-HPV types 16, 18, 31, and 33 2. D. High-risk HPV produce E6 and E7 proteins which result in increased destruction of p53 and Rb, respectively. Loss of these tumor suppressor proteins increases the risk for CIN. Fig. 13.2B Vaginal adenosis. Fig. 13.3 Embryonal rhabdomyosarcoma. (Courtesy of hum path.corn) III. CERVICAL INTRAEPITHELIAL NEOPLASIA A. Characterized by koilocytic change, disordered cellular maturation, nuclear atypia, and increased mitotic activity within the cervical epithelium. B. Divided into grades based on the extent of epithelial involvement by immature dysplastic cells 1.


Pathoma_Husain

Pathoma_Husain. B. Divided into grades based on the extent of epithelial involvement by immature dysplastic cells 1. CIN I involves < 1/3 of the thickness of the epithelium. 2. CIN II involves < 2/3 of the thickness of the epithelium. 3. CIN III involves slightly less than the entire thickness of the epithelium (Fig. 13.4B). 4. Carcinoma in situ (CIS) involves the entire thickness of the epithelium. C. CIN classically progresses in a stepwise fashion through CIN I, CIN II, CIN III, and CIS to become invasive squamous cell carcinoma. 1. Progression is not inevitable (e.g., CINI often regresses). 2. The higher the grade of dysplasia, the more likely it is to progress to carcinoma and the less likely it is to regress to normal. IV. A. Invasive carcinoma that arises from the cervical epithelium B. Most commonly seen in middle-aged women (average age is 40-50 years) C. Presents as vaginal bleeding, especially postcoital bleeding, or cervical discharge


Pathoma_Husain

Pathoma_Husain. B. Most commonly seen in middle-aged women (average age is 40-50 years) C. Presents as vaginal bleeding, especially postcoital bleeding, or cervical discharge D. Key risk factor is high-risk HPV infection; secondary risk factors include smoking and immunodeficiency (e.g., cervical carcinoma is an AIDS-defining illness). E. Most common subtypes of cervical carcinoma are squamous cell carcinoma (80% of cases) and adenocarcinoma (15% of cases). Both types are related to HPV infection. F. Advanced tumors often invade through the anterior uterine wall into the bladder, blocking the ureters. Hydronephrosis with postrenal failure is a common cause of death in advanced cervical carcinoma. V. A. The goal of screening is to catch dysplasia (CIN) before it develops into carcinoma. 1. Progression from CIN to carcinoma, on average, takes 10-20 years. 2. Screening begins at age 21 and is initially performed every three years. B. Pap smear is the gold standard for screening. 1.


Pathoma_Husain

Pathoma_Husain. Progression from CIN to carcinoma, on average, takes 10-20 years. 2. Screening begins at age 21 and is initially performed every three years. B. Pap smear is the gold standard for screening. 1. Cells are scraped from the transformation zone using a brush and analyzed under a microscope. 2. Dysplastic cells are classified as low grade (CIN I) or high grade (CIN II and III). 3. High-grade dysplasia is characterized by cells with hyperchromatic (dark) nuclei and high nuclear to cytoplasmic ratios (Fig. 13.4C). C. Pap smear is the most successful screening test developed to date. Fig. 13.4 Cervix. A, Cervical transformation zone, normal. B, CIN Ill. C, High-grade dysplasia, Pap smear. (Courtesy of Ed Uthman, MD) 1. It is responsible for a significant reduction in the morbidity and mortality of cervical carcinoma (cervical carcinoma went from being the most common to one of the least common types of gynecologic carcinoma in the US). 2.


Pathoma_Husain

Pathoma_Husain. 2. Women who develop invasive cervical carcinoma usually have not undergone screening. D. An abnormal Pap smear is followed by confirmatory colposcopy (visualization of cervix with a magnifying glass) and biopsy. E. Limitations of the Pap smear include inadequate sampling of the transformation zone (false negative screening) and limited efficacy in screening for adenocarcinoma. 1. Despite Pap smear screening, the incidence of adenocarcinoma has not decreased significantly. F. Immunization is effective in preventing HPV infections. 1. The quadrivalent vaccine covers HPV types 6, 11, 16, and 18. 2. Antibodies generated against types 6 and 11 protect against condylomas. 3. Antibodies generated against types 16 and 18 protect against CIN and carcinoma. 4. Pap smears are still necessary due to the limited number ofHPV types covered by the vaccine. I. BASIC PRINCIPLES A. Endometrium is the mucosa I lining of the uterine cavity.


Pathoma_Husain

Pathoma_Husain. 4. Pap smears are still necessary due to the limited number ofHPV types covered by the vaccine. I. BASIC PRINCIPLES A. Endometrium is the mucosa I lining of the uterine cavity. B. Myometrium is the smooth muscle wall underlying the endometrium (Fig. 13.5). C. Endometrium is hormonally sensitive. 1. Growth of the endometrium is estrogen driven (proliferative phase). 2. Preparation of the endometrium for implantation is progesterone driven (secretory phase). 3. Shedding occurs with loss of progesterone support (menstrual phase). II. ASHERMAN SYNDROME A. Secondary amenorrhea due to loss of the basalis and scarring B. Result of overaggressive dilation and curettage (D&C) III. ANOVULATORY CYCLE A. Lack of ovulation B. Results in an estrogen-driven proliferative phase without a subsequent progesteronedriven secretory phase 1. Proliferative glands break down and shed resulting in uterine bleeding.


Pathoma_Husain

Pathoma_Husain. B. Results in an estrogen-driven proliferative phase without a subsequent progesteronedriven secretory phase 1. Proliferative glands break down and shed resulting in uterine bleeding. Fig. 13.5 Endometrium overlying myometrium, Fig. 13.6 Endometrial polyp. normal. 2. Represents a common cause of dysfunctional uterine bleeding, especially during menarche and menopause IV. A. Bacterial infection of the endometrium B. Usually due to retained products of conception (e.g., after delivery or miscarriage); retained products act as a nidus for infection. C. Presents as fever, abnormal uterine bleeding, and pelvic pain V. A. Chronic inflammation of the endometrium B. Characterized by lymphocytes and plasma cells 1. Plasma cells are necessary for the diagnosis of chronic endometritis given that lymphocytes are normally found in the endometrium. C. Causes include retained products of conception, chronic pelvic inflammatory disease (e.g., Chlamydia), IUD, and TB.


Pathoma_Husain

Pathoma_Husain. C. Causes include retained products of conception, chronic pelvic inflammatory disease (e.g., Chlamydia), IUD, and TB. D. Presents as abnormal uterine bleeding, pain, and infertility VI. ENDOMETRIAL POLYP A. Hyperplastic protrusion of endometrium (Fig. 13.6) B. Presents as abnormal uterine bleeding C. Can arise as a side effect of tamoxifen, which has anti-estrogenic effects on the breast but weak pro-estrogenic effects on the endometrium VII. ENDOMETRIOSIS A. Endometrial glands and stroma outside of the uterine endometrial lining 1. Most likely due to retrograde menstruation with implantation at an ectopic site B. Presents as dysmenorrhea (pain during menstruation) and pelvic pain; may cause infertility 1. Endometriosis cycles just like normal endometrium. C. Most common site of involvement is the ovary, which classically results in formation of a 'chocolate' cyst (Fig. 13.7A). 1.


Pathoma_Husain

Pathoma_Husain. C. Most common site of involvement is the ovary, which classically results in formation of a 'chocolate' cyst (Fig. 13.7A). 1. Other sites of involvement include the uterine ligaments (pelvic pain), pouch of Douglas (pain with defecation), bladder wall (pain with urination), bowel serosa (abdominal pain and adhesions), and fallopian tube mucosa (scarring increases risk for ectopic tubal pregnancy); implants classically appear as yellow-brown 'gun-powder' nodules (Fig. 13.7B). 2. Involvement of the uterine myometrium is called adenomyosis. D. There is an increased risk of carcinoma at the site ofendometriosis, especially in the ovary. Fig. 13.7 Endometriosis. A, 'Chocolate cyst' of ovary. B, 'Gun powder' nodules. (A, Courtesy of Bulent Fig. 13.8 Endometrial hyperplasia. (Courtesy of Celasun, MD. B, Courtesy of hum path.com) Ed Uthman, MD) VIII. ENDOMETRIAL HYPERPLASIA A. Hyperplasia ofendometrial glands relative to stroma (Fig. 13.8)


Pathoma_Husain

Pathoma_Husain. VIII. ENDOMETRIAL HYPERPLASIA A. Hyperplasia ofendometrial glands relative to stroma (Fig. 13.8) B. Occurs as a consequence of unopposed estrogen (e.g., obesity, polycystic ovary syndrome, and estrogen replacement) C. Classically presents as postmenopausal uterine bleeding D. Classified histologically based on architectural growth pattern (simple or complex) and the presence or absence of cellular atypia 1. Most important predictor for progression to carcinoma (major complication) is the presence of cellular atypia; simple hyperplasia with atypia often progresses to cancer (30%); whereas, complex hyperplasia without atypia rarely does (<5%). IX. A. Malignant proliferation of endometrial glands (Fig. 13.9A) 1. Most common invasive carcinoma of the female genital tract B. Presents as postmenopausal bleeding C. Arises via two distinct pathways: hyperplasia and sporadic D. In the hyperplasia pathway (75% of cases), carcinoma arises from endometrial hyperplasia. 1.


Pathoma_Husain

Pathoma_Husain. C. Arises via two distinct pathways: hyperplasia and sporadic D. In the hyperplasia pathway (75% of cases), carcinoma arises from endometrial hyperplasia. 1. Risk factors are related to estrogen exposure and include early menarche/late menopause, nulliparity, infertility with anovulatory cycles, and obesity. 2. Average age ofpresentation is 60 years. 3. Histology is endometrioid (i.e., normal endometrium-like, Fig. 13.9B). E. In the sporadic pathway (25% of cases), carcinoma arises in an atrophic endometrium with no evident precursor lesion. 1. Average age at presentation is 70 years. 2. Histology is usually serous and is characterized by papillary structures (Fig. 13.9C) with psammoma body formation; p53 mutation is common, and the tumor exhibits aggressive behavior. X. A. Benign neoplastic proliferation of smooth muscle arising from myometrium; most common tumor in females B. Related to estrogen exposure 1. 2. 3.


Pathoma_Husain

Pathoma_Husain. X. A. Benign neoplastic proliferation of smooth muscle arising from myometrium; most common tumor in females B. Related to estrogen exposure 1. 2. 3. C. Gross exam shows multiple, well-defined, white, whorled masses that may distort the uterus and impinge on pelvic structures (Fig. 13.10). D. Usually asymptomatic; when present, symptoms include abnormal uterine bleeding, infertility, and a pelvic mass. Fig. 13.9 Endometrial carcinoma. A, Gross appearance. B, Endometrioid type. C, Serous type. (A, Courtesy of www.anatomiapatologica.com.br) XI. LEIOMYOSARCOMA A. Malignant proliferation of smooth muscle arising from the myometrium B. Arises de novo; leiomyosarcomas do not arise from leiomyomas. C. Usually seen in postmenopausal women D. Gross exam often shows a single lesion with areas of necrosis and hemorrhage; histological features include necrosis, mitotic activity, and cellular atypia. I. BASIC PRINCIPLES A. The functional unit of the ovary is the follicle.


Pathoma_Husain

Pathoma_Husain. I. BASIC PRINCIPLES A. The functional unit of the ovary is the follicle. B. A follicle consists of an oocyte surrounded by granulosa and theca cells (Fig. 13.llA) 1. LH acts on theca cells to induce androgen production. 2. FSH stimulates granulosa cells to convert androgen to estradiol (drives the proliferative phase of the endometrial cycle). 3. Estradiol surge induces an LH surge, which leads to ovulation (marking the beginning of the secretory phase of the endometrial cycle). C. After ovulation, the residual follicle becomes a corpus luteum (Fig. 13.llB), which primarily secretes progesterone (drives the secretory phase which prepares the endometrium for a possible pregnancy). 1. Hemorrhage into a corpus luteum can result in a hemorrhagic corpus luteal cyst, especially during early pregnancy. D. Degeneration of follicles results in follicular cysts. Small numbers of follicular cysts are common in women and have no clinical significance.


Pathoma_Husain

Pathoma_Husain. D. Degeneration of follicles results in follicular cysts. Small numbers of follicular cysts are common in women and have no clinical significance. II. POLYCYSTIC OVARIAN DISEASE (PCOD) A. Multiple ovarian follicular cysts due to hormone imbalance 1. Affects roughly 5% of women of reproductive age B. Characterized by increased LH and low FSH (LH:FSH > 2) 1. Increased LH induces excess androgen production (from theca cells) resulting in hirsutism (excess hair in a male distribution). 2. Androgen is converted to estrone in adipose tissue. i. Estrone feedback decreases FSH resulting in cystic degeneration of follicles. ii. High levels of circulating estrone increase risk for endometrial carcinoma. C. Classic presentation is an obese young woman with infertility, oligomenorrhea, and hirsutism; some patients have insulin resistance and may develop type 2 diabetes mellitus 10-15 years later.


Pathoma_Husain

Pathoma_Husain. C. Classic presentation is an obese young woman with infertility, oligomenorrhea, and hirsutism; some patients have insulin resistance and may develop type 2 diabetes mellitus 10-15 years later. Fig. 13.10 Uterine leiomyomas. (Courtesy of Fig. 13.11 Ovarian follicle. A, Normal. B, Corpus luteum. (B, Courtesy of Ed Uthman, MD) Jamie Steinmetz, MD) I. BASIC PRINCIPLES A. Ovary is composed of three cell types: surface epithelium, germ cells, and sex cordstroma. B. Tumor can arise from any of these cell types or from metastases. II. SURFACE EPITHELIAL TUMORS A. Most common type of ovarian tumor (70% of cases) B. Derived from coelomic epithelium that lines the ovary; coelomic epithelium embryologically produces the epithelial lining of the fallopian tube (serous cells), endometrium, and endocervix (mucinous cells). C. The two most common subtypes of surface epithelial tumors are serous and mucinous; both are usually cystic. 1. Serous tumors are full ofwatery fluid. 2.


Pathoma_Husain

Pathoma_Husain. C. The two most common subtypes of surface epithelial tumors are serous and mucinous; both are usually cystic. 1. Serous tumors are full ofwatery fluid. 2. Mucinous tumors are full of mucus-like fluid. D. Mucinous and serous tumors can be benign, borderline, or malignant. 1. Benign tumors (cystadenomas) are composed of a single cyst with a simple, flat lining (Fig. 13.12); most commonly arise in premenopausal women (30 -40 years old) 2. Malignant tumors (cystadenocarcinomas) are composed of complex cysts with a thick, shaggy lining; most commonly arise in postmenopausal women (60-70 years old) 3. Borderline tumors have features in between benign and malignant tumors. i. Better prognosis than clearly malignant tumors, but still carry metastatic potential 4. BRCAl mutation carriers have an increased risk for serous carcinoma of the ovary and fallopian tube.


Pathoma_Husain

Pathoma_Husain. i. Better prognosis than clearly malignant tumors, but still carry metastatic potential 4. BRCAl mutation carriers have an increased risk for serous carcinoma of the ovary and fallopian tube. 1. BRCAl carriers often elect to have a prophylactic salpingo-oophorectomy (along with prophylactic mastectomy due to the increased risk for breast cancer). E. Less common subtypes of surface epithelial tumors include endometrioid and Brenner tumor. 1. Endometrioid tumors are composed of endometrial-like glands and are usually malignant. i. May arise from endometriosis ii. 15% of endometrioid carcinomas of the ovary are associated with an independent endometrial carcinoma (endometrioid type). 2. Brenner tumors are composed of bladder-like epithelium and are usually benign. F. Surface tumors clinically present late with vague abdominal symptoms (pain and fullness) or signs of compression (urinary frequency). Fig. 13.12 Ovarian cystadenoma. 1.


Pathoma_Husain

Pathoma_Husain. F. Surface tumors clinically present late with vague abdominal symptoms (pain and fullness) or signs of compression (urinary frequency). Fig. 13.12 Ovarian cystadenoma. 1. Prognosis is generally poor for surface epithelial carcinoma (worst prognosis of female genital tract cancers). 2. Epithelial carcinomas tend to spread locally, especially to the peritoneum. G. CA-125 is a useful serum marker to monitor treatment response and screen for recurrence. III. GERM CELL TUMORS A. 2nd most common type of ovarian tumor (15% of cases) B. Usually occur in women of reproductive age C. Tumor subtypes mimic tissues normally produced by germ cells. 1. 2. 3. 4. D. Cystic teratoma 1. Cystic tumor composed of fetal tissue derived from two or three embryo logic layers (e.g., skin, hair, bone, cartilage, gut, and thyroid, Fig. 13.13) i. Most common germ cell tumor in females; bilateral in 10% of cases 2.


Pathoma_Husain

Pathoma_Husain. Benign, but presence of immature tissue (usually neural) or somatic malignancy (usually squamous cell carcinoma of skin) indicates malignant potential. 3. Struma ovarii is a teratoma composed primarily of thyroid tissue. E. Dysgerminoma 1. Tumor composed oflarge cells with clear cytoplasm and central nuclei (resemble oocytes, Fig. 13.14); most common malignant germ cell tumor 2. Testicular counterpart is called seminoma, which is a relatively common germ cell tumor in males. 3. Good prognosis; responds to radiotherapy 4. Serum LDH may be elevated. F. Endodermal sinus tumor 1. Malignant tumor that mimics the yolk sac; most common germ cell tumor in children 2. Serum AFP is often elevated. 3. Schiller-Duval bodies (glomerulus-like structures) are classically seen on histology (Fig. 13.15). G. Choriocarcinoma 1. Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts; mimics placental tissue, but villi are absent 2.


Pathoma_Husain

Pathoma_Husain. G. Choriocarcinoma 1. Malignant tumor composed of cytotrophoblasts and syncytiotrophoblasts; mimics placental tissue, but villi are absent 2. Small, hemorrhagic tumor with early hematogenous spread 3. High P-hCG is characteristic (produced by syncytiotrophoblasts); may lead to thecal cysts in the ovary Fig. 13.13 Cystic teratoma. Fig. 13.14 Dysgermin oma. Fig. 13.15 Schiller-Duval body. (Courtesy webpathology.com) 4. Poor response to chemotherapy H. Embryonal carcinoma 1. 2. Aggressive with early metastasis IV. A. Tumors that resemble sex cord-stromal tissues of the ovary B. Granulosa-theca cell tumor 1. Neoplastic proliferation of granulosa and theca cells 2. Often produces estrogen; presents with signs of estrogen excess 1. Prior to puberty-precocious puberty 11. Reproductive age-menorrhagia or metrorrhagia iii. Postmenopause (most common setting for granulosa-theca cell tumors)endometrial hyperplasia with postmenopausal uterine bleeding 3.


Pathoma_Husain

Pathoma_Husain. Malignant, but minimal risk for metastasis C. Sertoli-Leydig cell tumor 1. Composed of Sertoli cells that form tubules and Leydig cells (between tubules) with characteristic Reinke crystals 2. May produce androgen; associated with hirsutism and virilization D. Fibroma 1. Benign tumor of fibroblasts (Fig. 13.16) 2. Associated with pleural effusions and ascites (Meigs syndrome); syndrome resolves with removal of tumor. V. A. Krukenberg tumor is a metastatic mucinous tumor that involves both ovaries; most commonly due to metastatic gastric carcinoma (diffuse type) 1. Bilaterality helps distinguish metastases from primary mucinous carcinoma of the ovary, which is usually unilateral. B. Pseudomyxoma peritonei is massive amounts of mucus in the peritoneum. 1. Due to a mucinous tumor of the appendix, usually with metastasis to the ovary I. ECTOPIC PREGNANCY


Pathoma_Husain

Pathoma_Husain. B. Pseudomyxoma peritonei is massive amounts of mucus in the peritoneum. 1. Due to a mucinous tumor of the appendix, usually with metastasis to the ovary I. ECTOPIC PREGNANCY A. Implantation of fertilized ovum at a site other than the uterine wall; most common site is the lumen of the fallopian tube (Fig. 13.17). B. Key risk factor is scarring (e.g., secondary to pelvic inflammatory disease or endometriosis). Fig. 13.16 Ovarian fibroma. Fig. 13.17 Ectopic tubal pregnancy. (Courtesy of humpath.com) C. Classic presentation is lower quadrant abdominal pain a few weeks after a missed period. 1. Surgical emergency; major complications are bleeding into fallopian tube (hematosalpinx) and rupture. II. SPONTANEOUS ABORTION A. Miscarriage of fetus occurring before 20 weeks gestation (usually during first trimester) 1. Common; occurs in up to 1/4 of recognizable pregnancies B. Presents as vaginal bleeding, cramp-like pain, and passage of fetal tissues


Pathoma_Husain

Pathoma_Husain. B. Presents as vaginal bleeding, cramp-like pain, and passage of fetal tissues C. Most often due to chromosomal anomalies (especially trisomy 16); other causes include hypercoagulable states (e.g., antiphospholipid syndrome), congenital infection, and exposure to teratogens (especially during the first 2 weeks of embryogenesis). 1. Effect of teratogens generally depends on the dose, agent, and time of exposure (Table 12.1). i. First two weeks of gestation-spontaneous abortion ii. Weeks 3-8-risk of organ malformation iii. Months 3-9-risk of organ hypoplasia III. PLACENTA PREVIA A. Implantation of the placenta in the lower uterine segment; placenta overlies cervical os (opening). B. Presents as third-trimester bleeding C. Often requires delivery of fetus by caesarian section IV. A. Separation of placenta from the decidua prior to delivery of the fetus (Fig. 13.18) B. Common cause of still birth C. Presents with third-trimester bleeding and fetal insufficiency V.


Pathoma_Husain

Pathoma_Husain. IV. A. Separation of placenta from the decidua prior to delivery of the fetus (Fig. 13.18) B. Common cause of still birth C. Presents with third-trimester bleeding and fetal insufficiency V. A. Improper implantation of placenta into the myometrium with little or no intervening decidua B. Presents with difficult delivery of the placenta and postpartum bleeding Table 12.1: Common Teratogens and Associated Effects Most common cause of mental retardation; also leads to facial lsotretinoin Spontaneous abortion, hearing and visual impairment C. Often requires hysterectomy VI. PREECLAMPSIA A. Pregnancy-induced hypertension, proteinuria, and edema, usually arising in the third trimester; seen in approximately 5% of pregnancies 1. Hypertension may be severe, leading to headaches and visual abnormalities. B. Due to abnormality of the maternal-fetal vascular interface in the placenta; resolves with delivery C. Eclampsia is preeclampsia with seizures.


Pathoma_Husain

Pathoma_Husain. B. Due to abnormality of the maternal-fetal vascular interface in the placenta; resolves with delivery C. Eclampsia is preeclampsia with seizures. D. HELLP is preeclampsia with thrombotic microangiopathy involving the liver; characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets E. Both eclampsia and HELLP usually warrant immediate delivery. VII. SUDDEN INFANT DEATH SYNDROME A. Death of a healthy infant (1 month to 1 year old) without obvious cause B. Infants usually expire during sleep C. Risk factors include sleeping on stomach, exposure to cigarette smoke, and prematurity. VIII. HYDATIDIFORM MOLE A. Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts Table 12.2: Features of Complete and Partial Moles Some villi are hydropic, and some Villous edema Most villi are hydropic (Fig. 13.19B). are normal.


Pathoma_Husain

Pathoma_Husain. Table 12.2: Features of Complete and Partial Moles Some villi are hydropic, and some Villous edema Most villi are hydropic (Fig. 13.19B). are normal. Trophoblastic Focal proliferation present around Diffuse, circumferential proliferation hydropic villi proliferation around hydropic villi Fig. 13.18 Placental abruption. (Courtesy of Fig. 13.19 Complete mole. A, Swollen, 'grape-like' villi. B, Hydropic villi. (A, Courtesy of Steven Jerome Taxy, MD) O'Connor, MD) B. Uterus expands as if a normal pregnancy is present, but the uterus is much larger and ~-hCG much higher than expected for date of gestation. C. Classically presents in the second trimester as passage of grape-like masses through the vaginal canal (Fig. 13.19A). 1. With prenatal care, moles are diagnosed by routine ultrasound in the early first trimester. Fetal heart sounds are absent, and a 'snowstorm' appearance is classically seen on ultrasound. D. Classified as complete or partial (Table 12.2)


Pathoma_Husain

Pathoma_Husain. D. Classified as complete or partial (Table 12.2) E. Treatment is suction curettage. 1. Subsequent p-hCG monitoring is important to ensure adequate mole removal and to screen for the development of choriocarcinoma. 1. Choriocarcinoma may arise as a complication of gestation (spontaneous abortion, normal pregnancy, or hydatidiform mole) or as a spontaneous germ cell tumor. ii. Choriocarcinomas that arise from the gestational pathway respond well to chemotherapy; those that arise from the germ cell pathway do not.


Pathoma_Husain

Pathoma_Husain. ii. Choriocarcinomas that arise from the gestational pathway respond well to chemotherapy; those that arise from the germ cell pathway do not. Thank you for choosing Pathoma for your studies. We strive to provide the highest quality educational materials while keeping affordability in mind. A tremendous amount of time and effort has gone into developing these materials, so we appreciate your legitimate use of this program. It speaks to your integrity as a future physician and the high ethical standards that we all set forth for ourselves when taking the Hippocratic oath. Unauthorized use of Pathoma materials is contrary to the ethical standards of a training physician and is a violation of copyright. Pathoma videos are updated on a regular basis and the most current version, as well as a complete list of errata, can be accessed through your account at Pathoma.com. Sincerely, Dr. Sattar, MD I. HYPOSPADIAS A. Opening of urethra on inferior surface of penis


Pathoma_Husain

Pathoma_Husain. Pathoma.com. Sincerely, Dr. Sattar, MD I. HYPOSPADIAS A. Opening of urethra on inferior surface of penis B. Due to failure of the urethral folds to close II. EPISPADIAS A. Opening of urethra on superior surface of penis B. Due to abnormal positioning of the genital tubercle C. Associated with bladder exstrophy III. CONDYLOMA ACUMINATUM A. Benign warty growth on genital skin B. Due to HPV type 6 or 11; characterized by koilocytic change (Fig. 14.1) IV. A. Necrotizing granulomatous inflammation of the inguinal lymphatics and lymph nodes B. Sexually transmitted disease caused by Chlamydia trachomatis (serotypes Ll-L3) C. Eventually heals with fibrosis; perianal involvement may result in rectal stricture. V. A. Malignant proliferation of squamous cells of penile skin B. Risk factors 1. High risk HPV (2/3 of cases) 2. Lack of circumcision-Foreskin acts as a nidus for inflammation and irritation if not properly maintained. C. Precursor in situ lesions 1.


Pathoma_Husain

Pathoma_Husain. B. Risk factors 1. High risk HPV (2/3 of cases) 2. Lack of circumcision-Foreskin acts as a nidus for inflammation and irritation if not properly maintained. C. Precursor in situ lesions 1. Bowen disease-in situ carcinoma of the penile shaft or scrotum that presents as leukoplakia 2. Erythroplasia of Queyrat-in situ carcinoma on the glans that presents as erythroplakia 3. Bowenoid papulosis-in situ carcinoma that presents as multiple reddish papules i. Seen in younger patients (40s) relative to Bowen disease and erythroplasia of Queyrat ii. Does not progress to invasive carcinoma I. CRYPTORCHIDISM A. Failure of testicle to descend into the scrotal sac 1. Testicles normally develop in the abdomen and then "descend" into the scrotal sac as the fetus grows. B. Most common congenital male reproductive abnormality; seen in 1% of male infants pathoma.com C. Most cases resolve spontaneously; otherwise, orchiopexy is performed before 2 years of age.


Pathoma_Husain

Pathoma_Husain. B. Most common congenital male reproductive abnormality; seen in 1% of male infants pathoma.com C. Most cases resolve spontaneously; otherwise, orchiopexy is performed before 2 years of age. D. Complications include testicular atrophy with infertility and increased risk for seminoma. II. ORCHITIS A. Inflammation of the testicle B. Causes 1. Chlamydia trachomatis (serotypes D-K) or Neisseria gonorrhoeae-Seen in young adults. Increased risk of sterility, but libido is not affected because Leydig cells are spared. 2. Escherichia coli and Pseudomonas-Seen in older adults; urinary tract infection pathogens spread into the reproductive tract. 3. Mumps virus (teenage males)-increased risk for infertility; testicular inflammation is usually not seen in children < 10 years old. 4. Autoimmune orchitis-characterized by granulomas involving the seminiferous tubules III. TESTICULAR TORSION


Pathoma_Husain

Pathoma_Husain. 4. Autoimmune orchitis-characterized by granulomas involving the seminiferous tubules III. TESTICULAR TORSION A. Twisting of the spermatic cord; thin-walled veins become obstructed leading to congestion and hemorrhagic infarction (Fig. 14.2). B. Usually due to congenital failure of testes to attach to the inner lining of the scrotum (via the processus vaginalis) C. Presents in adolescents with sudden testicular pain and absent cremasteric reflex IV. A. Dilation of the spermatic vein due to impaired drainage B. Presents as scrotal swelling with a "bag of worms" appearance C. Usually left sided; left testicular vein drains into the left renal vein, while the right testicular vein drains directly into the IVC. 1. Associated with left-sided renal cell carcinoma; RCC often invades the renal vein. D. Seen in a large percentage of infertile males V.


Pathoma_Husain

Pathoma_Husain. 1. Associated with left-sided renal cell carcinoma; RCC often invades the renal vein. D. Seen in a large percentage of infertile males V. A. Fluid collection within the tunica vaginalis 1. Tunica vaginalis is a serous membrane that covers the testicle as well as the internal surface of the scrotum. B. Associated with incomplete closure of the processus vaginalis leading to communication with the peritoneal cavity (infants) or blockage oflymphatic drainage (adults) Fig . 14.1 Koilocytic change. Fig. 14.2 Hemorrhagic infarction of testicle. Fig. 14.3 Hydrocele. (Courtesy of humpath.com) C. Presents as scrotal swelling that can be transilluminated (Fig. 14.3) I. BASIC PRINCIPLES A. Arise from germ cells or sex cord-stroma B. Present as a firm, painless testicular mass that cannot be transilluminated C. Usually not biopsied due to risk of seeding the scrotum; removed via radical orchiectomy 1. Most testicular tumors are malignant germ cell tumors. II. GERM CELL TUMORS


Pathoma_Husain

Pathoma_Husain. C. Usually not biopsied due to risk of seeding the scrotum; removed via radical orchiectomy 1. Most testicular tumors are malignant germ cell tumors. II. GERM CELL TUMORS A. Most common type of testicular tumor(> 95% of cases) B. Usually occur between 15-40 years of age C. Risk factors include cryptorchidism and Klinefelter syndrome. D. Divided into seminoma and nonseminoma 1. Seminomas (55% of cases) are highly responsive to radiotherapy, metastasize late, and have an excellent prognosis. 2. Nonseminomas (45% of cases) show variable response to treatment and often metastasize early. E. Seminoma is a malignant tumor comprised oflarge cells with clear cytoplasm and central nuclei (resemble spermatogonia, Fig. 14.4A); forms a homogeneous mass with no hemorrhage or necrosis (Fig. 14.4B) 1. 2. Rare cases may produce ~-hCG. 3. Good prognosis; responds to radiotherapy


Pathoma_Husain

Pathoma_Husain. 2. Rare cases may produce ~-hCG. 3. Good prognosis; responds to radiotherapy F. Embryonal carcinoma is a malignant tumor comprised of immature, primitive cells that may produce glands (Fig. 14.SA); forms a hemorrhagic mass with necrosis (Fig. 14.SB) 1. Aggressive with early hematogenous spread 2. Chemotherapy may result in differentiation into another type of germ cell tumor (e.g., teratoma). 3. Increased AFP or ~-hCG may be present. G. Yolk sac (endodermal sinus) tumor is a malignant tumor that resembles yolk sac elements. 1. 2. Schiller-Duval bodies (glomerulus-like structures) are seen on histology (Fig. 14.6). 3. AFP is characteristically elevated. Fig. 14.4 Seminoma. A, Microscopic appearance. B, Gross appearance. (A, Courtesy of Ed Uthman, MD) H. Choriocarcinoma is a malignant tumor of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue, but villi are absent, Fig. 14.7). 1. 2.


Pathoma_Husain

Pathoma_Husain. H. Choriocarcinoma is a malignant tumor of syncytiotrophoblasts and cytotrophoblasts (placenta-like tissue, but villi are absent, Fig. 14.7). 1. 2. ~-hCG is characteristically elevated; may lead to hyperthyroidism or gynecomastia (a-subunit ofhCG is similar to that ofFSH, LH, and TSH) I. Teratoma is a tumor composed of mature fetal tissue derived from two or three embryonic layers. 1. Malignant in males (as opposed to females) 2. AFP or ~-hCG may be increased. J. Mixed germ cell tumors 1. Germ cell tumors are usually mixed. 2. Prognosis is based on the worst component. Ill. SEX CORD-STROMAL TUMORS A. Tumors that resemble sex cord-stromal tissues of the testicle (Fig. 14.8); usually benign B. Leydig cell tumor usually produces androgen, causing precocious puberty in children or gynecomastia in adults. 1. Characteristic Reinke crystals may be seen on histology. C. Sertoli cell tumor is comprised of tubules and is usually clinically silent. IV. LYMPHOMA


Pathoma_Husain

Pathoma_Husain. 1. Characteristic Reinke crystals may be seen on histology. C. Sertoli cell tumor is comprised of tubules and is usually clinically silent. IV. LYMPHOMA A. Most common cause of a testicular mass in males > 60 years old; often bilateral B. Usually of diffuse large B-cell type Fig. 14.5 Embryonal carcinoma. A, Microscopic appearance. B, Gross appearance. (Courtesy of webpathology.com) Fig. 14.6 Schiller-Duval body, yolk sac tumor. Fig. 14.7 Choriocarcinoma. (Courtesy of Fig. 14.8 Normal testicle, microscopic (Courtesy of webpathology.com) web pathology.com) appearance. I. BASIC PRINCIPLES A. Small, round organ that lies at the base of the bladder encircling the urethra B. Sits anterior to the rectum; posterior aspect of prostate is palpable by digital rectal exam (DRE). C. Consists of glands and stroma (Fig. 14.9) 1.


Pathoma_Husain

Pathoma_Husain. B. Sits anterior to the rectum; posterior aspect of prostate is palpable by digital rectal exam (DRE). C. Consists of glands and stroma (Fig. 14.9) 1. Glands are composed of an inner layer ofluminal cells and an outer layer of basal cells; secrete alkaline, milky fluid that is added to sperm and seminal vesicle fluid to make semen. 2. Glands and stroma are maintained by androgens. II. ACUTE PROSTATITIS A. Acute inflammation of the prostate; usually due to bacteria 1. Chlamydia trachomatis and Neisseria gonorrhoeae are common causes in young adults. 2. Escherichia coli and Pseudomonas are common causes in older adults. B. Presents as dysuria with fever and chills C. Prostate is tender and boggy on digital rectal exam. D. Prostatic secretions show WBCs; culture reveals bacteria. III. CHRONIC PROSTATITIS A. Chronic inflammation of prostate B. Presents as dysuria with pelvic or low back pain C. Prostatic secretions show WBCs, but cultures are negative.


Pathoma_Husain

Pathoma_Husain. III. CHRONIC PROSTATITIS A. Chronic inflammation of prostate B. Presents as dysuria with pelvic or low back pain C. Prostatic secretions show WBCs, but cultures are negative. IV. BENIGN PROSTATIC HYPERPLASIA (BPH) A. Hyperplasia of prostatic stroma and glands B. Age-related change (present in most men by the age of 60 years); no increased risk for cancer C. Related to dihydrotestosterone (DHT) 1. Testosterone is converted to DHT by Sa-reductase in stromal cells. 2. DHT acts on the androgen receptor of stromal and epithelial cells resulting in hyperplastic nodules. D. Occurs in the central periurethral zone of the prostate E. Clinical features include 1. 2. Impaired bladder emptying with increased risk for infection and hydronephrosis (Fig. 14.10) 3. Fig. 14.9 Normal prostate, microscopic Fig. 14.10 Hydronephrosis. appearance. 4. Hypertrophy of bladder wall smooth muscle; increased risk for bladder diverticula 5. Microscopic hematuria may be present. 6.


Pathoma_Husain

Pathoma_Husain. 4. Hypertrophy of bladder wall smooth muscle; increased risk for bladder diverticula 5. Microscopic hematuria may be present. 6. Prostate-specific antigen (PSA) is often slightly elevated (usually less than 10 ng/ mL) due to the increased number of glands; PSA is made by prostatic glands and liquefies semen. F. Treatment 1. a -antagonist (e.g., terazosin) to relax smooth muscle i. Also relaxes vascular smooth muscle lowering blood pressure ii. Selective a A -antagonists (e.g., tamsulosin) are used in normotensive individuals to avoid a effects on blood vessels. 2. 5a-reductase inhibitor i. Blocks conversion of testosterone to DHT ii. Takes months to produce results iii. Also useful for male pattern baldness iv. Side effects are gynecomastia and sexual dysfunction. V. PROSTATE ADENOCARCINOMA A. Malignant proliferation of prostatic glands B. Most common cancer in men; 2nd most common cause of cancer-related death


Pathoma_Husain

Pathoma_Husain. V. PROSTATE ADENOCARCINOMA A. Malignant proliferation of prostatic glands B. Most common cancer in men; 2nd most common cause of cancer-related death C. Risk factors include age, race (African Americans > Caucasians > Asians), and diet high in saturated fats . D. Prostatic carcinoma is most often clinically silent. 1. Usually arises in the peripheral, posterior region of the prostate and, hence, does not produce urinary symptoms early on (Fig. 14.llA) 2. Screening begins at the age of 50 years with DRE and PSA. i. Normal serum PSA increases with age due to BPH (2.5 ng/mL for ages 40-49 years vs. 7.5 ng/mL for ages 70-79 years) ii. PSA > 10 ng/mL is highly worrisome at any age. iii. Decreased% free-PSA is suggestive of cancer (cancer makes bound PSA). E. Prostatic biopsy is required to confirm the presence of carcinoma. 1. Shows small, invasive glands with prominent nucleoli (Fig. 14.llB) 2. Gleason grading system is based on architecture alone (and not nuclear atypia).


Pathoma_Husain

Pathoma_Husain. 1. Shows small, invasive glands with prominent nucleoli (Fig. 14.llB) 2. Gleason grading system is based on architecture alone (and not nuclear atypia). i. Multiple regions of the tumor are assessed because architecture varies from area to area. ii. A score (1-5) is assigned for two distinct areas and then added to produce a final score (2-10). iii. Higher score suggests worse prognosis. Fig. 14.11 Prostatic adenocarcinoma. A, Gross appearance. B, Microscopic appearance. C, Osteoblastic metastasis involving lumbar spine. F. Spread to lumbar spine or pelvis is common (Fig. 14.llC); results in osteoblastic metastases that present as low back pain and increased serum alkaline phosphatase, PSA, and prostatic acid phosphatase (PAP) G. Prostatectomy is performed for localized disease; advanced disease is treated with hormone suppression to reduce testosterone and DHT. 1.


Pathoma_Husain

Pathoma_Husain. G. Prostatectomy is performed for localized disease; advanced disease is treated with hormone suppression to reduce testosterone and DHT. 1. Continuous GnRH analogs (e.g., leuprolide) shut down the anterior pituitary gonadotrophs (LH and FSH are reduced). 2. Flutamide acts as a competitive inhibitor at the androgen receptor. I. ENDOCRINE SYSTEM A. Group of glands that maintain body homeostasis B. Functions by release of hormones that travel via blood to distant organs C. "Feedback" mechanisms control hormone release. I. PITUITARY ADENOMA A. Benign tumor of anterior pituitary cells B. May be functional (hormone-producing) or nonfunctional (silent) 1. Nonfunctional tumors often present with mass effect. i. Bitemporal hemianopsia occurs due to compression of the optic chiasm. ii. Hypopituitarism occurs due to compression of normal pituitary tissue. iii. Headache 2. Functional tumors present with features based on the type of hormone produced.


Pathoma_Husain

Pathoma_Husain. ii. Hypopituitarism occurs due to compression of normal pituitary tissue. iii. Headache 2. Functional tumors present with features based on the type of hormone produced. C. Prolactinoma presents as galactorrhea and amenorrhea (females) or as decreased libido and headache (males); most common type of pituitary adenoma 1. Treatment is dopamine agonists (e.g., bromocriptine or cabergoline) to suppress prolactin production (shrinks tumor) or surgery for larger lesions. D. Growth hormone cell adenoma 1. Gigantism in children-increased linear bone growth (epiphyses are not fused) 2. 1. Enlarged bones of hands, feet, and jaw ii. Growth of visceral organs leading to dysfunction (e.g., cardiac failure) iii. Enlarged tongue 3. Secondary diabetes mellitus is often present (GH induces liver gluconeogenesis). 4. Diagnosed by elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose 5.


Pathoma_Husain

Pathoma_Husain. 4. Diagnosed by elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose 5. Treatment is octreotide (somatostatin analog that suppresses GH release), GH receptor antagonists, or surgery. E. ACTH cell adenomas secrete ACTH leading to Cushing syndrome (see "Adrenal Cortex" below). F. TSH cell, LH-producing, and FSH-producing adenomas occur, but are rare. II. HYPOPITUITARISM A. Insufficient production of hormones by the anterior pituitary gland; symptoms arise when > 75% of the pituitary parenchyma is lost. B. Causes include 1. Pituitary adenomas (adults) or craniopharyngioma (children)-due to mass effect or pituitary apoplexy (bleeding into an adenoma) 2. Sheehan syndrome-pregnancy-related infarction of the pituitary gland i. Gland doubles in size during pregnancy, but blood supply does not increase significantly; blood loss during parturition precipitates infarction.


Pathoma_Husain

Pathoma_Husain. pathoma.com ii. Presents as poor lactation, loss of pubic hair, and fatigue 3. Empty sella syndrome-congenital defect of the sella i. Herniation of the arachnoid and CSF into the sella compresses and destroys the pituitary gland. ii. Pituitary gland is "absent" (empty sella) on imaging. I. BASIC PRINCIPLES A. Antidiuretic hormone (ADH) and oxytocin are made in the hypothalamus and then transported via axons to the posterior pituitary for release. 1. ADH acts on the distal tubules and collecting ducts of the kidney to promote free water retention. 2. Oxytocin mediates uterine contraction during labor and release of breast milk (let-down) in lactating mothers. II. CENTRAL DIABETES INSIPIDUS A. ADH deficiency B. Due to hypothalamic or posterior pituitary pathology (e.g., tumor, trauma, infection, or inflammation) C. Clinical features are based on loss of free water. 1. Polyuria and polydipsia with risk oflife-threatening dehydration 2. 3.


Pathoma_Husain

Pathoma_Husain. C. Clinical features are based on loss of free water. 1. Polyuria and polydipsia with risk oflife-threatening dehydration 2. 3. D. Water deprivation test fails to increase urine osmolality (useful for diagnosis). E. Treatment is desmopressin (ADH analog). III. NEPHROGENIC DIABETES INSIPIDUS A. Impaired renal response to ADH B. Due to inherited mutations or drugs (e.g., lithium and demeclocycline) C. Clinical features are similar to central diabetes insipidus, but there is no response to desmopressin. IV. SYNDROME OF INAPPROPRIATE ADH (SIADH) SECRETION A. Excessive ADH secretion B. Most often due to ectopic production (e.g., small cell carcinoma of the lung); other causes include CNS trauma, pulmonary infection, and drugs (e.g., cyclophosphamide). C. Clinical features are based on retention of free water. 1. 2. Mental status changes and seizures-Hyponatremia leads to neuronal swelling and cerebral edema. D. Treatment is free water restriction or demeclocycline.


Pathoma_Husain

Pathoma_Husain. 1. 2. Mental status changes and seizures-Hyponatremia leads to neuronal swelling and cerebral edema. D. Treatment is free water restriction or demeclocycline. I. THYROGLOSSAL DUCT CYST A. Cystic dilation of thyroglossal duct remnant 1. Thyroid develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck. 2. Thyroglossal duct normally involutes; a persistent duct, however, may undergo cystic dilation. B. Presents as an anterior neck mass II. LINGUAL THYROID A. Persistence of thyroid tissue at the base of tongue B. Presents as a base of tongue mass I. BASIC PRINCIPLES A. Increased level of circulating thyroid hormone 1. Increases basal metabolic rate (due to increased synthesis of Na+ -K+ ATPase) 2. Increases sympathetic nervous system activity (due to increased expression of ~ -adrenergic receptors) B. Clinical features include 1. 2. 3. Tachycardia with increased cardiac output 4.


Pathoma_Husain

Pathoma_Husain. Increases sympathetic nervous system activity (due to increased expression of ~ -adrenergic receptors) B. Clinical features include 1. 2. 3. Tachycardia with increased cardiac output 4. Arrhythmia (e.g., atrial fibrillation), especially in the elderly 5. Tremor, anxiety, insomnia, and heightened emotions 6. Staring gaze with lid lag 7. Diarrhea with malabsorption 8. 9. Bone resorption with hypercalcemia (risk for osteoporosis) 10. Decreased muscle mass with weakness 11. 12. Hyperglycemia (due to gluconeogenesis and glycogenolysis) II. GRAVES DISEASE A. Autoantibody (IgG) that stimulates TSH receptor (type II hypersensitivity) B. Leads to increased synthesis and release of thyroid hormone 1. Most common cause of hyperthyroidism 2. Classically occurs in women of childbearing age (20-40 years) C. Clinical features include 1. 2. Diffuse goiter-Constant TSH stimulation leads to thyroid hyperplasia and hypertrophy (Fig. 15.lA). 3.


Pathoma_Husain

Pathoma_Husain. C. Clinical features include 1. 2. Diffuse goiter-Constant TSH stimulation leads to thyroid hyperplasia and hypertrophy (Fig. 15.lA). 3. 1. Fibroblasts behind the orbit and overlying the shin express the TSH receptor. ii. TSH activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema. Fig. 15.1 Graves disease. A, Diffuse goiter. B, Microscopic appearance. (A, Courtesy of Ed Uthman, MD) D. Irregular follicles with scalloped colloid and chronic inflammation are seen on histology (Fig. 15.lB). E. Laboratory findings include 1. t total and free T ; ..l, TSH (free T downregulates TRH receptors in the anterior pituitary to decrease TSH release) 2. 3. F. Treatment involves P-blockers, thioamide, and radioiodine ablation. G. Thyroid storm is a potentially fatal complication. 1.


Pathoma_Husain

Pathoma_Husain. 3. F. Treatment involves P-blockers, thioamide, and radioiodine ablation. G. Thyroid storm is a potentially fatal complication. 1. Due to elevated catecholamines and massive hormone excess, usually in response to stress (e.g., surgery or childbirth) 2. Presents as arrhythmia, hyperthermia, and vomiting with hypovolemic shock 3. Treatment is propylthiouracil (PTU), P-blockers, and steroids. i. PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 to T3. III. MULTINODULAR GOITER A. Enlarged thyroid gland with multiple nodules (Fig. 15.2) B. Due to relative iodine deficiency C. Usually nontoxic (euthyroid) D. Rarely, regions become TSH-independent leading to T release and hyperthyroidism ('toxic goiter'). I. CRETINISM A. Hypothyroidism in neonates and infants


Pathoma_Husain

Pathoma_Husain. C. Usually nontoxic (euthyroid) D. Rarely, regions become TSH-independent leading to T release and hyperthyroidism ('toxic goiter'). I. CRETINISM A. Hypothyroidism in neonates and infants B. Characterized by mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia 1. Thyroid hormone is required for normal brain and skeletal development. C. Causes include maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency. 1. Dyshormonogenetic goiter is due to a congenital defect in thyroid hormone production; most commonly involves thyroid peroxidase II. MYXEDEMA A. Hypothyroidism in older children or adults B. Clinical features are based on decreased basal metabolic rate and decreased sympathetic nervous system activity. 1. Myxedema-accumulation of glycosaminoglycans in the skin and soft tissue; results in a deepening ofvoice and large tongue 2. 3.


Pathoma_Husain

Pathoma_Husain. 1. Myxedema-accumulation of glycosaminoglycans in the skin and soft tissue; results in a deepening ofvoice and large tongue 2. 3. Slowing of mental activity 4. 5. Cold intolerance with decreased sweating 6. Bradycardia with decreased cardiac output, leading to shortness of breath and fatigue 7. 8. 9. C. Most common causes are iodine deficiency and Hashimoto thyroiditis; other causes include drugs (e.g., lithium) and surgical removal or radioablation of the thyroid. I. HASHIMOTO THYROIDITIS A. Autoimmune destruction of the thyroid gland; associated with HLA-DR5 1. Most common cause of hypothyroidism in regions where iodine levels are adequate B. Clinical features 1. Initially may present as hyperthyroidism (due to follicle damage) 2. Progresses to hypothyroidism; ,l., T4 and t TSH 3. Antithyroglobulin and antithyroid peroxidase antibodies are often present (sign of thyroid damage).


Pathoma_Husain

Pathoma_Husain. Progresses to hypothyroidism; ,l., T4 and t TSH 3. Antithyroglobulin and antithyroid peroxidase antibodies are often present (sign of thyroid damage). C. Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles) is seen on histology (Fig. 15.3). D. Increased risk for B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course II. SUBACUTE GRANULOMATOUS (DE QUERVAIN) THYROIDITIS A. Granulomatous thyroiditis that follows a viral infection B. Presents as a tender thyroid with transient hyperthyroidism C. Self-limited; rarely (15% of cases) may progress to hypothyroidism III. RIEDEL FIBROSING THYROIDITIS A. Chronic inflammation with extensive fibrosis of the thyroid gland B. Presents as hypothyroidism with a 'hard as wood,' non tender thyroid gland C. Fibrosis may extend to involve local structures (e.g., airway).


Pathoma_Husain

Pathoma_Husain. B. Presents as hypothyroidism with a 'hard as wood,' non tender thyroid gland C. Fibrosis may extend to involve local structures (e.g., airway). 1. Clinically mimics anaplastic carcinoma, but patients are younger (40s), and malignant cells are absent I. BASIC PRINCIPLES A. Usually presents as a distinct, solitary nodule 1. Thyroid nodules are more likely to be benign than malignant. B. 13 1I radioactive uptake studies are useful to further characterize nodules. 1. Increased uptake ('hot' nodule) is seen in Graves disease or nodular goiter. 2. Decreased uptake ('cold' nodule) is seen in adenoma and carcinoma; often warrants biopsy C. Biopsy is performed by fine needle aspiration (FNA). II. FOLLICULAR ADENOMA A. Benign proliferation of follicles surrounded by a fibrous capsule (Fig. 15.4) Fig. 15.2 Multinodular goiter. (Courtesy of Jamie Fig. 15.3 Hashimoto thyroiditis. Fig. 15.4 Follicular adenoma. Steinmetz, MD)


Pathoma_Husain

Pathoma_Husain. Fig. 15.2 Multinodular goiter. (Courtesy of Jamie Fig. 15.3 Hashimoto thyroiditis. Fig. 15.4 Follicular adenoma. Steinmetz, MD) B. Usually nonfunctional; less commonly, may secrete thyroid hormone III. PAPILLARY CARCINOMA A. Most common type of thyroid carcinoma (80% of cases) B. Exposure to ionizing radiation in childhood is a major risk factor. C. Comprised of papillae lined by cells with clear, 'Orphan Annie eye' nuclei and nuclear grooves (Fig. 15.5A); papillae are often associated with psammoma bodies (Fig. 15.5B). D. Often spreads to cervical (neck) lymph nodes, but prognosis is excellent (10-year survival > 95%) IV. A. Malignant proliferation of follicles surrounded by a fibrous capsule with invasion through the capsule (Fig. 15.6) 1. Invasion through the capsule helps distinguish follicular carcinoma from follicular adenoma. 2. Entire capsule must be examined microscopically. 3.


Pathoma_Husain

Pathoma_Husain. Invasion through the capsule helps distinguish follicular carcinoma from follicular adenoma. 2. Entire capsule must be examined microscopically. 3. FNA only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNA. B. Metastasis generally occurs hematogenously. V. A. Malignant proliferation of parafollicular C cells; comprises 5% of thyroid carcinomas 1. C cells are neuroendocrine cells that secrete calcitonin. 2. Calcitonin lowers serum calcium by increasing renal calcium excretion but is inactive at normal physiologic levels. 3. High levels of calcitonin produced by tumor may lead to hypocalcemia. 4. Calcitonin often deposits within the tumor as amyloid. B. Biopsy reveals sheets of malignant cells in an amyloid stroma (Fig. 15.7). C. Familial cases are often due to multiple endocrine neoplasia (MEN) 2A and 2B, which are associated with mutations in the RET oncogene. 1.


Pathoma_Husain

Pathoma_Husain. C. Familial cases are often due to multiple endocrine neoplasia (MEN) 2A and 2B, which are associated with mutations in the RET oncogene. 1. MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B). 2. Detection of the RET mutation warrants prophylactic thyroidectomy. VI. ANAPLASTIC CARCINOMA A. Undifferentiated malignant tumor of the thyroid (Fig. 15.8); usually seen in elderly B. Often invades local structures, leading to dysphagia or respiratory compromise C. Poor prognosis Fig. 15.5 Papillary carcinoma. A, Nuclear features. B, Psammoma bodies. Fig. 15.6 Follicular carcinoma. (Courtesy of Bu lent Celasun, MD) I. BASIC PRINCIPLES A. Chief cells regulate serum free (ionized) calcium via parathyroid hormone (PTH) secretion, which 1. Increases bone osteoclast activity, releasing calcium and phosphate 2. Increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D) 3.


Pathoma_Husain

Pathoma_Husain. Increases bone osteoclast activity, releasing calcium and phosphate 2. Increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D) 3. B. Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion. II. PRIMARY HYPERPARATHYROIDISM A. Excess PTH due to a disorder of the parathyroid gland itself B. Most common cause is parathyroid adenoma (>80% of cases); sporadic parathyroid hyperplasia and parathyroid carcinoma are less common causes. C. Parathyroid adenoma is a benign neoplasm, usually involving one gland.


Pathoma_Husain

Pathoma_Husain. C. Parathyroid adenoma is a benign neoplasm, usually involving one gland. 1. Most often results in asymptomatic hypercalcemia; however, may present with consequences of increased PTH and hypercalcemia such as i. Nephrolithiasis (calcium oxalate stones) ii. Nephrocalcinosis-metastatic calcification of renal tubules (Fig. 15.9), potentially leading to renal insufficiency and polyuria 111. CNS disturbances (e.g., depression and seizures) 1v. Constipation, peptic ulcer disease, and acute pancreatitis v. Osteitis fibrosa cystica-resorption of bone leading to fibrosis and cystic spaces (Fig. 15.10) 2. Laboratory findings include t serum PTH, t serum calcium, J,. serum phosphate, t urinary cAMP, and t serum alkaline phosphatase. 3. Treatment involves surgical removal of the affected gland. III. SECONDARY HYPERPARATHYROIDISM A. Excess production of PTH due to a disease process extrinsic to the parathyroid gland B. Most common cause is chronic renal failure. 1.


Pathoma_Husain

Pathoma_Husain. III. SECONDARY HYPERPARATHYROIDISM A. Excess production of PTH due to a disease process extrinsic to the parathyroid gland B. Most common cause is chronic renal failure. 1. Renal insufficiency leads to decreased phosphate excretion. 2. t serum phosphate binds free calcium. 3. J,. free calcium stimulates all four parathyroid glands. 4. t PTH leads to bone resorption (contributing to renal osteodystrophy). 5. Lab findings include t PTH, J,. serum calcium, t serum phosphate, and t alkaline phosphatase. Fig. 15.7 Medullary carcinoma. Fig. 15.8 Ana plastic carcinoma. Fig. 15.9 Nephrocalcinosis. IV. HYPOPARATHYROIDISM A. LowPTH B. Causes include autoimmune damage to the parathyroids, surgical excision, and DiGeorge syndrome C. Presents with symptoms related to low serum calcium 1. 2. Muscle spasms (tetany)-may be elicited with filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign)


Pathoma_Husain

Pathoma_Husain. 2. Muscle spasms (tetany)-may be elicited with filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign) D. Labs reveal .,J, PTH levels and .,J, serum calcium. E. Pseudohypoparathyroidism is due to end-organ resistance to PTH. 1. Labs reveal hypocalcemia with t PTH levels. 2. Autosomal dominant form is associated with short stature and short 4th and 5th digits. I. BASIC PRINCIPLES A. Composed of clusters of cells termed islets of Langerhans (Fig. 15.11) B. A single islet consists of multiple cell types, each producing one type of hormone. C. Insulin is secreted by beta cells, which lie in the center of the islets. 1. 2. Increased glucose uptake by tissues leads to increased glycogen synthesis, protein synthesis, and lipogenesis. D. Glucagon is secreted by alpha cells; it opposes insulin in order to increase blood glucose levels (e.g., in states of fasting) via glycogenolysis and lipolysis.


Pathoma_Husain

Pathoma_Husain. D. Glucagon is secreted by alpha cells; it opposes insulin in order to increase blood glucose levels (e.g., in states of fasting) via glycogenolysis and lipolysis. A. Insulin deficiency leading to a metabolic disorder characterized by hyperglycemia B. Due to autoimmune destruction of beta cells by T lymphocytes 1. Characterized by inflammation of islets 2. Associated with HLA-DR3 and HLA-DR4 3. Autoantibodies against insulin are often present (sign of damage) and may be seen years before clinical disease develops. C. Manifests in childhood with clinical features of insulin deficiency 1. High serum glucose-Lack of insulin leads to decreased glucose uptake by fat and skeletal muscle. Fig. 15.10 Osteitis fibrosa cystica. Fig. 15.11 Islets of Langerhans. Fig. 15.12 Amyloid in islets, type II DM. 2. Weight loss, low muscle mass, and polyphagia-Unopposed glucagon leads to gluconeogenesis, glycogenolysis and lipolysis, which further exacerbates hyperglycemia. 3.


Pathoma_Husain

Pathoma_Husain. 2. Weight loss, low muscle mass, and polyphagia-Unopposed glucagon leads to gluconeogenesis, glycogenolysis and lipolysis, which further exacerbates hyperglycemia. 3. Polyuria, polydipsia, and glycosuria-Hyperglycemia exceeds renal ability to resorb glucose; excess filtered glucose leads to osmotic diuresis. 4. Treatment involves lifelong insulin. D. Risk for diabetic ketoacidosis 1. 2. Often arises with stress (e.g., infection); epinephrine stimulates glucagon secretion increasing lipolysis (along with gluconeogenesis and glycogenolysis). i. Increased lipolysis leads to increased free fatty acids (FFAs). ii. Liver converts FFAs to ketone bodies (~-hydroxybutyric acid and acetoacetic acid). 3. Results in hyperglycemia (> 300 mg/dL), anion gap metabolic acidosis, and hyperkalemia 4. Presents with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone) 5.


Pathoma_Husain

Pathoma_Husain. Presents with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone) 5. Treatment is fluids (corrects dehydration from polyuria), insulin, and replacement of electrolytes (e.g., potassium). Ill. TYPE 2 DIABETES MELLITUS A. End-organ insulin resistance leading to a metabolic disorder characterized by hyperglycemia 1. Most common type of diabetes (90% of cases); affects 5-10% of the US population 2. Incidence is rising. B. Arises in middle-aged, obese adults 1. Obesity leads to decreased numbers of insulin receptors. 2. Strong genetic predisposition exists. C. Insulin levels are increased early in disease, but later, insulin deficiency develops due to beta cell exhaustion; histology reveals amyloid deposition in the islets (Fig. 15.12). D. Clinical features include polyuria, polydipsia, and hyperglycemia, but disease is often clinically silent.


Pathoma_Husain

Pathoma_Husain. D. Clinical features include polyuria, polydipsia, and hyperglycemia, but disease is often clinically silent. E. Diagnosis is made by measuring glucose levels (normal is 70-120 mg/dL). 1. 2. 3. Glucose tolerance test with a serum glucose level > 200 mg/dL two hours after glucose loading F. Treatment involves weight loss (diet and exercise) initially; may require drug therapy to counter insulin resistance (e.g., sulfonylureas or metformin) or exogenous insulin after exhaustion of beta cells G. Risk for hyperosmolar non-ketotic coma 1. High glucose (> 500 mg/dL) leads to life-threatening diuresis with hypotension and coma. 2. Ketones are absent due to small amounts of circulating insulin. IV. LONG-TERM CONSEQUENCES OF DIABETES A. Nonenzymatic glycosylation (NEG) ofvascular basement membranes 1. NEG oflarge-and medium-sized vessels leads to atherosclerosis and its resultant complications. i. Cardiovascular disease is the leading cause of death among diabetics.


Pathoma_Husain

Pathoma_Husain. i. Cardiovascular disease is the leading cause of death among diabetics. ii. Peripheral vascular disease in diabetics is the leading cause of non traumatic amputations. 2. NEG of small vessels (arterioles) leads to hyaline arteriolosclerosis (Fig. 15.13A). i. Involvement of renal arterioles leads to glomerulosclerosis, resulting in small, scarred kidneys with a granular surface (Fig. 15.13B). ii. Preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury with microalbuminuria that eventually progresses to nephrotic syndrome; characterized by Kimmelstiel-Wilson nodules in glomeruli 3. NEG of hemoglobin produces glycated hemoglobin (HbA1c), a marker of glycemic control. B. Osmotic damage 1. Glucose freely enters into Schwann cells (which myelinate peripheral nerves), pericytes of retinal blood vessels, and the lens. 2. Aldose reductase converts glucose to sorbitol, resulting in osmotic damage. 3.


Pathoma_Husain

Pathoma_Husain. 2. Aldose reductase converts glucose to sorbitol, resulting in osmotic damage. 3. Leads to peripheral neuropathy, impotence, blindness, and cataracts; diabetes is the leading cause of blindness in the developed world. V. PANCREATIC ENDOCRINE NEOPLASMS A. Tumors of islet cells; account for < 5% of pancreatic neoplasms. 1. Often a component of MEN 1 along with parathyroid hyperplasia and pituitary adenomas B. Insulinomas present as episodic hypoglycemia with mental status changes that are relieved by administration of glucose. 1. Diagnosed by -l.-serum glucose levels (usually < 50 mg/dL), t insulin, and t C-peptide C. Gastrinomas present as treatment-resistant peptic ulcers (Zollinger-Ellison syndrome); ulcers may be multiple and can extend into the jejunum. D. Somatostatinomas present as achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin).


Pathoma_Husain

Pathoma_Husain. D. Somatostatinomas present as achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin). E. VIPomas secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria. I. BASIC PRINCIPLES A. Composed of three layers; each secretes predominantly one class of hormones. 1. Glomerulosa produces mineralocorticoids (e.g., aldosterone). 2. Fasciculata produces glucocorticoids (e.g., cortisol). 3. Reticularis produces weak androgens (e.g., DHEA). B. Cortical hormones are derived from cholesterol. Fig. 15.13 Complications of diabetes. A, Hyaline arteriolosclerosis. B, Glomerul osclerosis. 1. Sequential enzymatic modification produces mineralocorticoids, glucocorticoids, and androgens (Fig. 15.14). 2. Each layer secretes distinct hormones based on enzymes present in that layer. II. HYPERALDOSTERONISM A. Excess aldosterone


Pathoma_Husain

Pathoma_Husain. 2. Each layer secretes distinct hormones based on enzymes present in that layer. II. HYPERALDOSTERONISM A. Excess aldosterone B. Classically presents as HTN, hypokalemia, and metabolic alkalosis 1. Aldosterone increases absorption of sodium and secretion of potassium and hydrogen ions in the distal tubule and collecting duct. 2. Increased sodium expands plasma volume leading to HTN. C. Primary hyperaldosteronism is most commonly due to bilateral adrenal hyperplasia (60%, Fig. 15.15) or adrenal adenoma (40%, Conn syndrome, Fig. 15.16); adrenal carcinoma is rare. 1. CT is useful to determine pathology 2. Treatment for bilateral adrenal hyperplasia is mineralocorticoid receptor antagonist (e.g., spironolactone or eplerenone); adenoma and carcinoma are surgically resected. D. Secondary hyperaldosteronism arises with activation of the renin-angiotensin system (e.g., renovascular hypertension or CHF). Fig. 15.14 Steroidogenesis, adrenal cortex.


Pathoma_Husain

Pathoma_Husain. D. Secondary hyperaldosteronism arises with activation of the renin-angiotensin system (e.g., renovascular hypertension or CHF). Fig. 15.14 Steroidogenesis, adrenal cortex. Fig. 15.15 Adrenal hyperplasia. Fig. 15.16 Adrena l adenoma. E. Primary and secondary hyperaldosteronism are distinguished by plasma renin and edema 1. Primary is characterized by low renin and no edema (aldosterone escape). 2. Secondary is characterized by high renin; edema is often present. F. Glucocorticoid-remediable aldosteronism (GRA) leads to familial hyperaldosteron ism 1. Aberrant expression of aldosterone synthase in the fasciculata due to genetic mutation; autosomal dominant 2. Classically presents as child with HTN and hypokalemia; aldosterone is high and renin is low. 3. Responds to dexamethasone; confirmed with genetic testing G. Liddle syndrome mimics hyperaldosteronism. 1. Decreased degradation of sodium channels in collecting tubules due to genetic mutation; autosomal dominant 2.


Pathoma_Husain

Pathoma_Husain. G. Liddle syndrome mimics hyperaldosteronism. 1. Decreased degradation of sodium channels in collecting tubules due to genetic mutation; autosomal dominant 2. Presents as child with HTN, hypokalemia, and metabolic alkalosis, but with low aldosterone and low renin 3. 4. Treatment is potassium-sparing diuretics (e.g., amiloride or triamterene), which block tubular sodium channels; spironolactone is not effective. H. Syndrome of apparent mineralocorticoid excess (SAME) also mimics hyperaldosteronism. 1. 11~-hydroxysteroid dehydrogenase 2 (ll~-HSD2) deficiency allows cortisol to activate renal aldosterone receptors; autosomal recessive 2. Presents as child with HTN, hypokalemia, and metabolic alkalosis, but with low aldosterone and low renin 3. 4. May also arise with licorice (glycyrrhetinic acid), which blocks ll~-HSD2 III. HYPERCORTISOLISM (CUSHING SYNDROME) A. Excess cortisol B. Clinical features include 1.


Pathoma_Husain

Pathoma_Husain. 4. May also arise with licorice (glycyrrhetinic acid), which blocks ll~-HSD2 III. HYPERCORTISOLISM (CUSHING SYNDROME) A. Excess cortisol B. Clinical features include 1. Muscle weakness with thin extremities-Cortisol breaks down muscle to produce amino acids for gluconeogenesis. 2. Moon facies, buffalo hump, and truncal obesity-High insulin (due to high glucose) increases storage of fat centrally. 3. Abdominal striae-Impaired collagen synthesis results in thinning of skin 4. HTN often with hypokalemia and metabolic alkalosis 1. High cortisol increases sensitivity of peripheral vessels to catecholamines. ii. At very high levels, cortisol cross-reacts with mineralocorticoid receptors (aldosterone is not increased). 5. 6. C. Diagnosis is based on 24-hour urine cortisol level (increased), late night salivary cortisol level (increased), and low-dose dexamethasone suppression test.


Pathoma_Husain

Pathoma_Husain. 5. 6. C. Diagnosis is based on 24-hour urine cortisol level (increased), late night salivary cortisol level (increased), and low-dose dexamethasone suppression test. 1. Low-dose dexamethasone suppresses cortisol in normal individuals but fails to suppress cortisol in all causes of Cushing syndrome. D. Plasma ACTH distinguishes ACTH-dependent causes of Cushing syndrome from ACTH-independent causes (table 15.1). 1. IfACTH-independent, next step is CT to look for an adrenal lesion. 2. IfACTH-dependent, next step is high-dose dexamethasone test. E. High-dose dexamethasone suppresses ACTH production by a pituitary adenoma (serum cortisol is lowered) but does not suppress ectopic ACTH production (serum cortisol remains high). _____________11111, Table 15.1 Cushing Syndrome Low NIA NIA Tapering of steroids, if possible


Pathoma_Husain

Pathoma_Husain. _____________11111, Table 15.1 Cushing Syndrome Low NIA NIA Tapering of steroids, if possible Transsphenoidal resection of pituitary ACTH-secreting adenoma; bilateral adrenalectomy in pituitary refractory cases can lead to enlargement adenoma (70%, of pituitary adenoma, resulting in may be present. Cushing disease) hyperpigmentation, headaches, and bitemporal hemianopsia (Nelson syndrome) Ectopic ACTH ACTH (e.g., small excess and No suppression Resection of ectopic source may be present. Adenomal Primary adrenal carcinoma with Resection of adenomalcarcinoma or adenoma (10%), contralateral Low NIA bilateral resection of hyperplasia with hyperplasia, or atrophy or F. Treatment generally involves surgical resection 1. Ketoconazole or metyrapone useful if surgery is not an option IV. CONGENITAL ADRENAL HYPERPLASIA A. Due to enzymatic defects in cortisol production; autosomal recessive 1. High ACTH (decreased negative feedback) leads to bilateral adrenal hyperplasia. 2.


Pathoma_Husain

Pathoma_Husain. IV. CONGENITAL ADRENAL HYPERPLASIA A. Due to enzymatic defects in cortisol production; autosomal recessive 1. High ACTH (decreased negative feedback) leads to bilateral adrenal hyperplasia. 2. Mineralocorticoids and androgens may be increased or decreased depending on the enzyme defect. B. 21-hydroxylase deficiency is the most common cause (90% of cases). 1. Aldosterone and cortisol are decreased; steroidogenesis is shunted towards androgens. 2. Classic form presents in neonates as hyponatremia and hyperkalemia with lifethreatening hypotension (salt-wasting type); females have clitoral enlargement (genital ambiguity). 3. Nonclassic form presents later in life with androgen excess leading to precocious puberty (males) or hirsutism with menstrual irregularities (females). C. 11-hydroxylase deficiency also leads to androgen excess, but weak mineralocorticoids (DOC) are increased. 1.


Pathoma_Husain

Pathoma_Husain. C. 11-hydroxylase deficiency also leads to androgen excess, but weak mineralocorticoids (DOC) are increased. 1. Deoxycorticosterone (DOC) leads to HTN (sodium retention) with mild hypokalemia; renin and aldosterone are low. 2. Clitoral enlargement is seen in females D. 17-hydroxylase deficiency leads to decreased cortisol and androgens. 1. Weak mineralocorticoids (DOC) are increased leading to HTN with mild hypokalemia; renin and aldosterone are low. 2. Decreased androgens lead to primary amenorrhea and lack of pubic hair (females) or ambiguous genitalia with undescended testes (males). E. Newborn screening for CAH via serum 17-hydroxyprogesterone is routine 1. 2. F. Treatment for CAH is glucocorticoids; mineralocorticoids (21-hydroxylase deficiency) or sex steroids (17-hydroxylase deficiency) given as necessary. V. ADRENAL INSUFFICIENCY A. Deficiency of adrenal hormones B. Acute insufficiency presents as weakness and shock. Causes include 1.


Pathoma_Husain

Pathoma_Husain. V. ADRENAL INSUFFICIENCY A. Deficiency of adrenal hormones B. Acute insufficiency presents as weakness and shock. Causes include 1. Abrupt withdrawal of glucocorticoids 2. Treatment of Cushing syndrome 3. Waterhouse-Friderichsen syndrome-hemorrhagic necrosis of the adrenal glands (Fig. 15.17), classically due to sepsis and DIC in young children with Neisseria meningitidis infection C. Chronic insufficiency (Addison disease) presents with vague, progressive symptoms such as hypotension, weakness, fatigue, nausea, vomiting, and weight loss. D. Addison disease most often arises with progressive adrenal damage. 1. Common causes include autoimmune destruction (most common cause in the West), TB (most common cause in the developing world), and metastatic carcinoma (e.g., from lung). 2. Autoimmune adrenalitis can be a component of autoimmune polyendocrine syndromes E. Addison disease may also arise with pituitary (secondary) or hypothalamic (tertiary) disease. 1.


Pathoma_Husain

Pathoma_Husain. 2. Autoimmune adrenalitis can be a component of autoimmune polyendocrine syndromes E. Addison disease may also arise with pituitary (secondary) or hypothalamic (tertiary) disease. 1. Hyperpigmentation (high ACTH) and hyperkalemia (low aldosterone) suggest primary adrenal insufficiency; secondary/tertiary insufficiency has no hyperpigmentation (low ACTH) and normal potassium (normal aldosterone). 2. Lack of ACTH response with metyrapone stimulation test supports a secondary or tertiary cause. 3. ACTH response with CRH stimulation test suggests hypothalamic (tertiary) disease. F. Treatment is glucocorticoids and mineralocorticoids. I. BASIC PRINCIPLES A. Composed of neural crest-derived chromaffin cells B. Main physiologic source of catecholamines (epinephrine and norepinephrine) II. PHEOCHROMOCYTOMA A. Tumor of chromaffin cells (Fig. 15.18) Fig. 15.17 Waterhouse-Friderichsen syndrome. Fig. 15.18 Pheochromocytoma. (Courtesy of (Courtesy of hum path.com) humpath.com)


Pathoma_Husain

Pathoma_Husain. II. PHEOCHROMOCYTOMA A. Tumor of chromaffin cells (Fig. 15.18) Fig. 15.17 Waterhouse-Friderichsen syndrome. Fig. 15.18 Pheochromocytoma. (Courtesy of (Courtesy of hum path.com) humpath.com) B. Clinical features are due to episodic release of catecholamines. 1. Episodic HTN, headaches, palpitations, tachycardia, and sweating C. Diagnosed by increased metanephrines and catecholamines in serum and urine D. Treatment is adrenalectomy. 1. Catecholamines may leak into the bloodstream upon manipulation of the tumor. 2. Phenoxybenzamine (irreversible a-blocker) followed by ~-blocker is administered preoperatively to prevent a hypertensive crisis. E. Often follows the 'rule of 10s:' 10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (e.g., organ of Zuckerkandl at the inferior mesenteric artery root or bladder wall) 1. Malignancy is defined by metastatic spread; patients require long-term follow-up