10.5826/dpc.1204a186
Introduction: Although textbooks provide the ideal clinical and histopathological findings, in practice we usually have fewer, and sometimes contradictory, findings to work with. Objectives: The primary goal of this study is to categorize the diagnoses of clinically challenging skin lesions, thereby identifying the most common diagnostic scenarios encountered by dermatopathologists in practice and the most perplexing differential diagnoses submitted by clinicians. Our secondary aim is to investigate how the case profile and clinician decision-making processes changed during the COVID-19 pandemic.Methods: We classified 2184 pathology reports into four major categories: inflammatory, neoplastic, non-diagnostic, and other. In each category, the three most frequently reported diagnoses were listed. For each listed diagnosis, the top 3 most frequently used differential diagnoses by the clinician prior to biopsy are listed. The period one year after and before the first nationally reported COVID-19 case was compared using the same classification.Results: The most common diagnoses and clinical differential diagnoses were listed for each category, with 45.4% being inflammatory and 27.4% being neoplastic diseases. Non-diagnostic reports accounted for 11.4% of all reports. The overall number of reports has decreased drastically since the pandemic, and the rates of keratinocytic and melanocytic neoplasms have increased, while the rates of other malignancies and spongiotic diseases have decreased.Conclusion: Although a trained eye can easily identify skin lesions when they are typical, even diseases we are familiar with can present atypically in real life. In these cases, histopathological examinations and clinicopathological correlation are critical in making an accurate diagnosis.
text/xml
2160-9381
2239
en
Mehmet Gamsızkan
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
COVID-19
Dermatopathological Correlation of Clinically Challenging Cutaneous Lesions: A Single Center Experience of 2184 cases
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-10-31
2021-12-09
2022-10-31
2022-12-02
e2022186
Dermatol Pract Concept
Introduction: Although textbooks provide the ideal clinical and histopathological findings, in practice we usually have fewer, and sometimes contradictory, findings to work with. Objectives: The primary goal of this study is to categorize the diagnoses of clinically challenging skin lesions, thereby identifying the most common diagnostic scenarios encountered by dermatopathologists in practice and the most perplexing differential diagnoses submitted by clinicians. Our secondary aim is to investigate how the case profile and clinician decision-making processes changed during the COVID-19 pandemic.Methods: We classified 2184 pathology reports into four major categories: inflammatory, neoplastic, non-diagnostic, and other. In each category, the three most frequently reported diagnoses were listed. For each listed diagnosis, the top 3 most frequently used differential diagnoses by the clinician prior to biopsy are listed. The period one year after and before the first nationally reported COVID-19 case was compared using the same classification.Results: The most common diagnoses and clinical differential diagnoses were listed for each category, with 45.4% being inflammatory and 27.4% being neoplastic diseases. Non-diagnostic reports accounted for 11.4% of all reports. The overall number of reports has decreased drastically since the pandemic, and the rates of keratinocytic and melanocytic neoplasms have increased, while the rates of other malignancies and spongiotic diseases have decreased.Conclusion: Although a trained eye can easily identify skin lesions when they are typical, even diseases we are familiar with can present atypically in real life. In these cases, histopathological examinations and clinicopathological correlation are critical in making an accurate diagnosis.
Mehmet Gamsızkan
2022/10/31
10.5826/dpc.1204a186
e2022186
 Department of Dermatology, Duzce University, Duzce, Turkey 
2160-9381
COVID-19
en
e2022186
- Palladino R, Migliatico I, Sgariglia R, et al. Thyroid fine-needle aspiration trends before, during, and after the lockdown: what we have learned so far from the COVID-19 pandemic. Endocrine. 2021;71(1):20-25. doi:10.1007/s12020-020-02559-z
Dermatopathological Correlation of Clinically Challenging Cutaneous Lesions: A Single Center Experience of 2184 cases
https://dpcj.org/index.php/dpc/article/download/2239/1772
      Dermatopathological Correlation of Clinically
     Challenging Cutaneous Lesions: a Single Center
               Experience of 2184 Cases
          Yunus Ozcan1, Emin Ozlu2, Ebru Karagun3, Belkiz Uyar2, Mehmet Gamsizkan4


1 Department of Dermatology, Duzce Ataturk State Hospital, Duzce, Turkey
2 Department of Dermatology, Faculty of Medicine, Duzce University, Duzce, Turkey
3 Department of Dermatology, Faculty of Medicine, Istinye University, Istanbul, Turkey
4 Department of Pathology, Faculty of Medicine, Duzce University, Duzce, Turkey



Key words: dermatology, dermatopathology, clinicopathological correlation, COVID-19
Citation: Ozcan Y, Ozlu E, Karagun E, Uyar B, Gamsizkan M. Dermatopathological Correlation of Clinically Challenging Cutaneous
Lesions: A Single Center Experience of 2184 cases. Dermatol Pract Concept. 2022;12(4):e2022186. DOI: https://doi.org/10.5826/
dpc.1204a186
Accepted: March 7, 2022; Published: October 2022
Copyright: ©2022 Ozcan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Yunus Ozcan, MD, Department of Dermatology, Duzce Ataturk State Hospital, Duzce, Turkey.
E-mail: yunusozcan18@gmail.com




  ABSTRACT             Introduction: Although a trained eye can easily identify typical skin lesions, histopathological exam-
                       ination and clinicopathological correlation are critical in challenging cases.
                       Objectives: The primary objective is to organize the final diagnoses reached following clinicopatho-
                       logical consensus in clinically challenging cutaneous lesions, identifying the most common diagnostic
                       scenarios encountered by dermatopathologists and discussing their diverse differentials submitted by
                       clinicians. The secondary objective is to investigate how the case profile and clinician decision-making
                       processes evolved during the COVID-19 pandemic.
                       Methods: Skin and mucosa samples collected by the dermatology department between 2016 and
                       2020 were classified based on pathology reports. For frequent diagnoses, preliminary diagnoses stated
                       by clinicians on pathology requisition forms were reviewed. The years preceding and following the
                       first nationally reported COVID-19 case were compared to investigate the pandemic’s impact on the
                       distribution of dermatology and dermatopathology cases.
                       Results: One thousand nine hundred and eighty-nine reports were classified into 4 major catego-
                       ries: inflammatory (49.8%), neoplastic (30.1%), other diseases (7.1%), and non-diagnostic (12.8%).
                       We further classified inflammatory diseases based on major tissue reaction patterns and neoplasms
                       based on cell origin. We analyzed the leading diagnoses in each category, discussed their differential




Original Article | Dermatol Pract Concept. 2022;12(4):e2022186                                                                      1
                     ­ iagnoses, and provided clinicians with clues to reduce errors in practice. Following the pandemic, the
                     d
                     overall number of pathology reports and patient admissions dropped dramatically, with significant
                     changes in case profiles.
                     Conclusions: We presented and discussed the frequently encountered confounding cases to sketch the
                     diagnostic landscape. In the authors’ experience, clinicopathological correlation can increase the rate
                     of reaching the diagnosis by up to 75.3%.




Introduction                                                      pandemic affected dermatology and dermatopathology prac-
                                                                  tice and case distribution.
A trained eye is essential in the identification of skin dis-
eases, yet even common dermatoses can manifest with per-
                                                                  Objectives
plexing lesions [1]. Moreover, a newly formed or regressed
rash may not exhibit the classic morphological features [2].      • Organizing the final diagnoses reached after clinicopath-
Patients may further complicate the problem by scratching           ological consensus in clinically challenging dermatol-
and irritating their lesions, or by self-treating with exoge-       ogy cases.
nous and endogenous substances [2]. A skin biopsy is one          • Identifying and discussing the alternative diagnoses that
of the most effective methods for reaching a diagnosis in           are more likely to be considered by clinicians prior to
challenging cases [3].                                              biopsy, and providing clues for dermatologists to reduce
    Histopathological examination, on the other hand, has a         error in practice.
different set of limitations to consider. Inadequate sampling,    • Investigating the effects of the pandemic on the case pro-
biopsy of an inappropriate location or performing the biopsy        file of dermatology and dermatopathology departments
at an early or late stage, can result in limited findings [4].      following the first nationally reported COVID-19 case.
Even with an adequate sample, histopathological examina-
tion alone may be insufficient to make a definitive diagnosis
                                                                  Methods
and may occasionally reveal findings that contradict clinical
information [4]. Another major issue is the clinician’s fail-     This research was conducted in a referral hospital, serving
ure to provide sufficient information about the patient or a      around half a million people annually. We classified the
breakdown in communication between the two departments            pathology reports of skin and mucosa samples collected
[5]. A successful final diagnosis is better achieved by linking   by the dermatology department between 2016 and 2020.
the clues through clinicopathological correlation [6].            All reports indicating a definitive diagnosis were classified
    A biopsy requisition form is filled out to transfer the       under inflammatory, neoplastic, or other diseases. Reports
clinical information needed by the pathologist to correctly       that lacked a diagnosis or a useful clue were categorized as
interpret the histopathological examination [7]. A properly       non-diagnostic. Samples that were insufficient or obtained
completed form will improve communication between the             for direct immunofluorescence investigations were excluded.
clinician and the pathologist, allowing for a more accurate          We further classified inflammatory diseases into six cate-
diagnosis [6]. Retrospective studies on the consistency of        gories based on major tissue reaction patterns, and neoplas-
clinical information and pathology results report complete        tic diseases into three categories based on cell origin. The
concordance in only 28.3%-68.0 % of cases [3,8–11]. Al-           remaining reports diagnosed a wide range of diseases and
though these studies emphasize the importance of clinico-         they were classified as “Other”. Reports demonstrating a
pathological correlation, they do not provide guidance about      specific inflammatory pattern without a definitive diagnosis
the diagnostic dilemmas frequently encountered by derma-          were still considered useful to clinicians and classified under
tologists and dermatopathologists in real-life scenarios.         that specific pattern as non-diagnostic (eg, granulomatous
    In this study, we classified the frequently encountered       pattern, non-diagnostic) (Figure 1).
challenging cases and their diagnoses after clinicopathologi-        The three most frequently reported diagnoses by pathol-
cal correlation. All cases were evaluated and concluded on a      ogists in each category were compiled. In addition, for each
case-by-case basis in weekly meetings with a dermatologist        diagnosis, we listed the three most common differential diag-
and a dermatopathologist. We also used clinical information       noses submitted by clinicians prior to biops.
from pathology requisition forms to determine the most               All comparisons examining the effects of the pan-
frequently considered alternative diagnoses by clinicians         demic were made in the years preceding and follow-
prior to biopsy. Finally, we investigated how the COVID-19        ing the first nationally reported COVID-19 case. We



2                                                                     Original Article | Dermatol Pract Concept. 2022;12(4):e2022186
                                                                 ALL REPORTS
                                                                   n=2184




                                    EXCLUDED:
                            INSUFFICENT SAMPLES N=40
                       DIRECT IMMUNOFLORESCENCE SAMPLES
                                      n=155



                     INFLAMMATORY                NEOPLASTIC
                        DISEASES                  DISEASES                     OTHERS                NON-DIAGNOSTIC
                         n=992                     n=600                        n=142                    n=255



                         GRANULOMATOUS               KERATINOCYTIC
                            DISEASES                  NEOPLASMS
                              n=42                       n=224



                           PSORIASIFORM              MELANOCYTIC
                             DISEASES                 NEOPLASMS
                              n=222                     n=143



                             LICHENOID
                                                      OTHER CELLS
                              DISEASES
                                                        n=233
                               n=256



                          VASCULOPATHIC
                             DISEASES
                              N=103



                            SPONGIOTIC
                             DISEASES
                              N=307



                         VESICULOBULLOUS
                             DISEASES
                               N=62


                  Figure 1. The categorization of pathology reports and the number of cases in each category.


compared the case profiles reached after clinicopatholog-               when appropriate. Statistical significance was d
                                                                                                                       ­ etermined by
ical consensus using the same classification method. We                 p v­ alues less than 0.05.
also compared how frequently we biopsied the patients

     Number of biopsies taken × 100  , and the percentage             Results
 Total number of clinical examinations 
                                                                        In the majority of categories, pathological diagnosis
of     dermatology       department       samples        sent      in   matched the most frequently submitted differential diag-
 Number of dermatogy samples × 100                                    nosis by clinicians. The second and third differentials were
 Total samples received by pathology  .      Next,     as     an
                                                                        the most difficult to distinguish clinically. As a result, they
­indicator of case diversity, we compared the number of differ-         were more frequently proposed as alternate diagnoses to
ent definitive diagnoses made. Finally, in order to determine           pathologists.
the distribution of cases presented in the dermatology outpa-               Inflammatory diseases accounted for 49.8 % of all re-
tient department, we classified the registered ICD-10 codes.            ports (Table 1 and Table 2). Looking at the subcategories, we
     SPSS v.26 was used for statistical analysis. The Chi-              discovered that granulomatous diseases accounted for 2.1%
square test for proportions or the Fishers’ exact test was used,        of all cases, psoriasiform diseases 11.1%, lichenoid diseases



Original Article | Dermatol Pract Concept. 2022;12(4):e2022186                                                                       3
    Table 1. Granulomatous, psoriasiform, and lichenoid diseases. The pathologist’s diagnosis and the
              three most frequently submitted clinical differential diagnoses prior to biopsy
    Number of Cases             Pathologist’s Diagnosis                      Clinician’s Differential Diagnoses
                                                 Granulomatous Diseases
15                     1- Granulomatous pattern, non-diagnostic    1- Sarcoidosis
                                                                   2- Kaposi’s sarcoma
                                                                   3- Mycobacterial infection (tuberculosis, leprosy, etc.)
13                     2- Granuloma annulare                       1- Granuloma annulare
                                                                   2- Erythema annulare centrifugum
                                                                   3- Sarcoidosis
7                      3- Sarcoidosis                              1- Sarcoidosis
                                                                   2- Cutaneous lymphoma
                                                                   3- Pseudolymphoma
                                                   Psoriasiform Diseases
92                     1- Psoriasis vulgaris and subtypes          1- Psoriasis vulgaris and other subtypes
                                                                   2- Lichen planus and variants
                                                                   3- Contact dermatitis
40                     2- Psoriasiform pattern, non-diagnostic     1- Psoriasis vulgaris and other subtypes
                                                                   2- Contact dermatitis
                                                                   3- Pityriasis rubra pilaris
30                     3- Parapsoriasis                            1- Parapsoriasis
                                                                   2- Mycosis fungoides
                                                                   3- Nummular dermatitis
                                                    Lichenoid Diseases
71                     1- Lichen planus                            1- Lichen planus and variants
                                                                   2- Contact dermatitis
                                                                   3- Lichenoid drug eruption
47                     2- Lichenoid pattern, non-diagnostic        1- Lichen planus
                                                                   2- Contact dermatitis
                                                                   3- Drug eruption
21                     3- Pigmented purpuric dermatosis            1- Pigmented purpuric dermatosis
                                                                   2- Mycosis fungoides
                                                                   3- Contact dermatitis




Table 2. Vasculopathic, spongiotic, and vesiculobullous diseases. The pathologist’s diagnosis and the
           three most frequently submitted clinical differential diagnoses prior to biopsy
     Number of Cases                    Pathologist’s Diagnosis                   Clinician’s Differential Diagnoses
                                                  Vasculopathic Diseases
47                        1- Leukocytoclastic vasculitis                    1- Cutaneous small-vessel vasculitis
                                                                            2- IgA vasculitis
                                                                            3- Pigmented purpuric dermatosis
23                        2- Ulcers of various causes                       1- Squamous cell carcinoma
                                                                            2- Pyoderma gangrenosum
                                                                            3- Perforating dermatoses
12                        3- IgA vasculitis                                 1- IgA vasculitis
                                                                            2- Leukocytoclastic vasculitis
                                                                            3- Not available
                                                    Spongiotic Diseases
102                       1- Spongiotic pattern, non-diagnostic             1- Mycosis fungoides
                                                                            2- Parapsoriasis
                                                                            3- Psoriasis vulgaris and other subtypes

                                                                                                               Table 2 continues



4                                                                  Original Article | Dermatol Pract Concept. 2022;12(4):e2022186
     Number of Cases                      Pathologist’s Diagnosis                      Clinician’s Differential Diagnoses
 101                         2- Contact dermatitis                               1- Contact dermatitis
                                                                                 2- Psoriasis vulgaris and other subtypes
                                                                                 3- Mycosis fungoides
 17                          3-Pityriasis rosea                                  1- Pityriasis rosea
                                                                                 2- Psoriasis vulgaris and other subtypes
                                                                                 3- Erythema annulare centrifugum
                                                      Vesiculobullous Diseases
 23                          1-Bullous pemphigoid                                1- Bullous pemphigoid
                                                                                 2- Pemphigus vulgaris
                                                                                 3- Dermatitis herpetiformis
 11                          2-Vesiculobullous pattern, non-diagnostic           1- Bullous pemphigoid
                                                                                 2- Pemphigus vulgaris
                                                                                 3- Allergic contact dermatitis
 9                           3-Pemphigus vulgaris                                1- Pemphigus vulgaris
                                                                                 2- Bullous pemphigoid
                                                                                 3- Pemphigus foliaceus



12.8%, vasculopathic diseases 5.1%, spongiotic diseases                The number of biopsies taken per 100 dermatological
15.4%, and vesiculobullous diseases 3.1%.                           examinations was reduced from 2.7 to 2.1. Furthermore, the
     Reports describing clues that point to a specific inflam-      percentage of skin and mucosa samples received by pathol-
matory pattern but do not provide a definitive diagnosis            ogy was reduced from 6.9 percent to 2.7 percent. The case
were among the top three in each category. This category            diversity was also reduced from 113 to 60 distinct definitive
was only replaced by ulcers of various causes in the vasculo-       diagnoses.
pathic reaction pattern. The ratio of these reports was found          Following the first nationally documented COVID-19
to be 0.7% for granulomatous diseases, 2% for psoriasiform          case, the number of admissions to the dermatology outpa-
diseases, 2.3% for lichenoid diseases, 1.1% for vasculo-            tient department decreased from 16,511 to 5,550 annually.
pathic diseases, 5.1% for spongiotic diseases, and 0.5 % for        For these admissions, the examining dermatologists regis-
vesiculobullous diseases.                                           tered a total of 21,820 and 6,953 ICD-10 codes, respectively.
     In 30.1% of all reports, a definitive diagnosis of neoplasia   The total number of diagnoses has decreased in every cate-
was made. Keratinocytic neoplasms accounted for 11.2%, me-          gory except vesiculobullous diseases, where the admission
lanocytic neoplasms 7.1%, and other cell-derived neoplasms          count was the same (81 per year). The incidence of eczem-
11.7% of all reports. Basal cell carcinoma, squamous cell car-      atous (including contact, atopic, seborrheic, and nummular
cinoma, malignant melanoma, and mycosis fungoides were              dermatitis, among others), infectious (viral, bacterial, fungal,
the most common malignant neoplasms reported (Table 3).             and parasitic), and vesiculobullous diseases (pemphigus and
     Other diseases accounted for 7.1% of total reports after       pemphigoid diseases), as well as urticaria & angioedema,
excluding inflammatory and neoplastic diseases. Clinicians          and drug-related eruptions, increased significantly. Adnexal
needed assistance distinguishing morphea from extragenital          diseases (acne, rosacea, hidradenitis suppurativa, hyperhy-
lichen sclerosus and mycosis fungoides, verrucas from verru-        drosis), papulosquamous diseases (psoriasis, pityriasis rubra
cous carcinoma and squamous cell carcinoma, and dermato-            pilaris, pityriasis rosea), pigmentation disorders (vitiligo,
phytes from erythema annulare centrifigum and psoriasis in          melasma, post-inflammatory hyperpigmentation among
this category (Table 4).                                            others), and benign neoplasms (seborrheic keratosis, mela-
     In total, 12.8% of all reports were unhelpful in terms of      nocytic nevi, various cyts, etc) all had a significant decrease
providing any diagnostic findings. The percentage of reports        in incidence (Figure 2).
that provided a single definitive diagnosis was 75.3%. Fi-
nally, 11.9% of reports contained diagnostic hints but did
                                                                    Conclusions
not provide a definitive diagnosis.
     Following a year of pandemic, the number of reports in         The majority of diagnostic traffic between dermatology and
each category dropped dramatically. The percentage of cases         pathology is driven by inflammatory (49.8%) and neoplas-
with spongiotic patterns has decreased, while the percentage        tic (30.1%) diseases. The remaining diseases accounted for
of cases with keratinocytic and melanocytic neoplasms has           7.1% of all reports and covered a broad diagnostic range
increased (Table 5).                                                that could not be classified in either of these two major



Original Article | Dermatol Pract Concept. 2022;12(4):e2022186                                                                    5
Table 3. Neoplasms of keratinocytic, melanocytic, and other cell origins. The pathologist’s diagnosis
       and the three most frequently submitted clinical differential diagnoses prior to biopsy
        Number of Cases                   Pathologist’s Diagnosis                  Clinician’s Differential Diagnoses
                                                     Keratinocytic Neoplasm
 78                                1-Basal cell carcinoma                   1- Basal cell carcinoma
                                                                            2- Squamous cell carcinoma
                                                                            3- Bowen’s disease
 57                                2-Squamous cell carcinoma                1- Squamous cell carcinoma
                                                                            2- Basal cell carcinoma
                                                                            3- Actinic keratosis
 38                                3-Actinic keratosis                      1- Actinic keratosis
                                                                            2- Squamous cell carcinoma
                                                                            3- Basal cell carcinoma
                                                      Melanocytic Neoplasm
 117                               1-Melanocytic nevus                      1- Melanocytic nevus
                                                                            2- Atypical melanocytic nevus
                                                                            3- Malignant melanoma
 8                                 2-Dysplastic nevus                       1- Atypical melanocytic nevus
                                                                            2- Malignant melanoma
                                                                            3- Melanocytic nevus
 5                                 3-Malignant melanoma                     1- Malignant melanoma
                                                                            2- Atypical melanocytic nevus
                                                                            3- Squamous cell carcinoma
                                             Neoplasms Caused by Other Cells
 68                                1-Acrochordon                            1- Acrochordon
                                                                            2- Melanocytic nevus
                                                                            3- Not available
 31                                2- Various cysts                         1- Epidermoid cyst
                                                                            2- Trichilemmal cyst
                                                                            3- Syringoma
 23                                3-Mycosis fungoides                      1- Mycosis fungoides
                                                                            2- Parapsoriasis
                                                                            3- Contact dermatitis


Table 4. The other diseases, excluding inflammatory and neoplastic. The pathologist’s diagnosis and
         the three most frequently submitted clinical differential diagnoses prior to biopsy
       Number of Cases              Pathologist’s Diagnosis                     Clinician’s Differential Diagnoses
 34                            1- Morphea                            1- Morphea
                                                                     2- Lichen sclerosus (extragenital)
                                                                     3- Mycosis fungoides
 25                            2- Verruca vulgaris                   1- Verruca vulgaris
                                                                     2- Verrucous carcinoma
                                                                     3- Squamous cell carcinoma
 19                            3- Dermatophytosis                    1- Tinea incognito
                                                                     2- Erythema annulare centrifugum
                                                                     3- Psoriasis vulgaris and other subtypes


categories. In total, 75.3% of cases had a definitive diagnosis   pathologists, and it has a wide range of clinical manifesta-
after clinicopathological correlation, while 11.9% of cases       tions, some more specific than others [12]. Although his-
only had diagnostic clues. Finally, 12.8% of reports yielded      topathological features are invaluable, it should be kept in
no diagnostic information.                                        mind that classical naked granulomas will not always be
     In granulomatous diseases, cutaneous sarcoidosis is a        encountered [13,14]. Clinically suggestive findings include
frequently investigated diagnosis by both clinicians and          the disappearance of background erythema with diascopy,



6                                                                     Original Article | Dermatol Pract Concept. 2022;12(4):e2022186
       Table 5. Classification of diagnoses reached after clinicopathological consensus in the years
          preceding (2019) and following (2020) the first nationally reported COVID-19 case
                                                                                                                             P
                                    2019, N (%)                  2020, N (%)                Difference (%)              (Two-tailed)
                                                       Inflammatory Diseases
 Granulomatous                        12 (1.8%)                   3 (2.1%)                         0.3                       0.737
 Lichenoid                            91 (14%)                   23 (16.5%)                        2.4                       0.507
 Psoriasiform                        72 (11.1%)                   11 (7.9%)                        -3.2                      0.291
 Spongiotic                          96 (14.8%)                   9 (6.4%)                         -8.3                      0.008
 Vasculopathic                        42 (6.4%)                   5 (3.5%)                         -2.8                      0.238
 Vesiculobullous                      35 (5.4%)                   10 (7.1%)                        1.7                       0.421
                                                         Neoplastic Diseases
 Keratinocytic                       68 (10.5%)                  21 (15.1%)                        4.5                       0.139
 Melanocytic                          21 (3.2%)                   12 (8.6%)                        5.3                       0.007
 Other cells                         90 (13.9%)                   14 (10%)                         -3.8                      0.270
 Other                                38 (5.8%)                   9 (6.4%)                         0.6                       0.843
 Non-diagnostic                      82 (12.6%)                  22 (15.8%)                        3.1                       0.334
 Total                               647(100%)                   139 (100%)



                         Adenexal Diseases*          17,2%                                                           14,9%
                   Eczematous Dermatoses*            24,4%                                                           26,9%
                        Infectious Diseases*         21,8%                                                           24,9%
                Papulosquamous Disorders*            5,8%                                                            4,9%
                        Lichenoid Eruptions          0,4%                                                            0,5%
                   Vesiculobullous Diseases*         0,4%                                                            1,2%
          Vasculitic & Vasculopathic Diseases        0,1%                                                            0,1%
                    Pigmentation Disorders*          3,5%                                                            1,9%
   Hair, Nail and Mucous Membrane Diseases           5,2%                                                            5,1%
                  Urticaria & Angioedema and         4,4%                                                            6,6%
                      Drug-related Eruptions*
                           Benign Neoplasms*         3,7%                                                            2,3%
       Premalignant & Malignant Neoplasms            1,7%                                                            1,6%
                                     Others*         11,5%                                                           9,1%
                                                0%               25%                 50%                   75%                  100%

                                                             Year 2019 Year 2020


Figure 2. Cases admitted to the dermatology outpatient department in the year preceding (2019) and following (2020) the first nationally
announced COVID-19 case.
* P (two-tailed) < 0.05.


revealing an apple-jelly color [15], and the appearance of             drugs, metals, foodstuffs, or systemic diseases), particularly in
orange-yellow structureless areas in a focal or diffuse pattern        the oral mucosa [17]. Although difficult, establishing a link
with dermatoscopy [16]. In dermatoscopy, vascular struc-               between exposure and disease, as well as the resolution of
tures may appear as linear or branching vessels, rarely dotted         lesions when the offending agent is removed, is strongly sug-
or glomerular. Other less common dermatoscopic findings                gestive, but the regression period may take months [17]. The
include dilated follicles, follicular plugs, yellow-white scales,      same holds true for lichenoid skin reactions [18]. Lichenoid
milia-like cysts, white structureless areas and crystalline            skin reactions are characterized by larger, eczematous papules,
structures [16].                                                       sometimes with a psoriasiform morphology, and Wickham’s
    Lichen planus and its variants can have overlapping clin-          striae may be absent [18]. Eczematizing lesions can become
ical presentations with diseases such as psoriasis, contact            widespread, resulting in increased desquamation [18]. It can
dermatitis, and lichenoid drug reactions. Clinical and histo-          manifest as a symmetrical (often photo-distributed) eruption
pathological findings may be insufficient to differentiate be-         on the trunk and extremities, with a tendency to leave post-in-
tween lichenoid diseases and lichenoid reactions (caused by            flammatory hyperpigmentation [18]. Follicular involvement



Original Article | Dermatol Pract Concept. 2022;12(4):e2022186                                                                         7
and atrophy of the eccrine glands’ dermal ducts may result in      study for a variety of inflammatory diseases. The most cru-
alopecia and anhidrosis [18].                                      cial aspect of making a diagnosis is combining the history
    Pigmented purpuric dermatosis is a capillaritis charac-        (particularly occupational) with the distribution of the le-
terized by petechiae, purpura, and brown-red discoloration         sions. Although patch testing is the gold standard in allergic
[19]. Mycosis fungoides is a T-cell cutaneous lymphoma             contact dermatitis, potential allergens should be evaluated in
with various clinical presentations [20]. Clinically, the skin     terms of clinical significance. The diagnosis of irritant con-
manifestations of these two diseases can sometimes overlap         tact dermatitis is usually made by exclusion [35].
[21]. According to some studies, pigmented purpuric derma-            In neoplastic diseases, the biopsies were mostly per-
tosis is a type of cutaneous lymphoma [22], and persistent         formed to either differentiate between premalignant (ac-
cases may be a precursor to mycosis fungoides [23]. Mycosis        tinic keratosis, Bowen’s disease) and malignant (basal and
fungoides should be suspected when there are generalized           squamous cell carcinoma, malignant melanoma, mycosis
purpuric lesions that extend beyond the lower extremities          fungoides) lesions or to confirm the diagnosis and guide the
and are accompanied by pruritus [24], as opposed to pig-           treatment. Thus the diagnostic spectrum is straightforward.
mented purpuric dermatosis, which is asymptomatic [25].            The relatively low number of dysplastic nevus and malig-
Additional studies, such as repeated biopsies, immunopatho-        nant melanoma cases could be explained by the fact that this
logic, cytogenetic, and gene rearrangement studies, should be      study only used data from the dermatology department, and
performed in doubtful cases [24].                                  patients are referred to surgery in doubtful cases to ensure
    Histopathological and immunofluorescent studies re-            careful control of surgical margins. Excision of small lesions,
main the gold standard in the diagnosis of vasculitic [26]         typically less than 5mm in size, accounts for the high number
and autoimmune bullous diseases [27]. They are correlated          of benign melanocytic nevi. The various neoplasms caused
with clinical history, physical examination, and other inves-      by other cells are mostly overshadowed by the abundance
tigations to distinguish from similar diseases and confirm         of benign proliferations (acrochordons and cysts) that are
the diagnosis. There is significant overlap between small          mostly submitted for legal concerns.
vessel vasculitides, making it difficult to distinguish these         The remaining reports diagnosed a wide range of dis-
diseases from skin lesions alone [28]. The presence of gas-        eases, with the most common goal being to distinguish mor-
trointestinal (nausea, vomiting, abdominal pain, melena),          phea from extra-genital lichen sclerosus, verruca vulgaris
renal (­nephrotic and nephritic syndrome), joint (arthritis, ar-   from verrucous or squamous cell carcinoma, and dermato-
thralgia) symptoms, and IgA accumulation in skin or kidney         phytosis from erythema annulare sentrifugum or psoriasis.
biopsies should raise the possibility of IgA vasculitis [28,29].      Circumscribed morphea appears as an oval plaque on the
­Although IgA vasculitis is most common between the ages           trunk with an ivory sclerotic center and erythematous-vio-
of 3 and 15, it can occur at any age between 5 months and          laceous borders [36]. It is associated with dyspigmentation
89 years old [28,29]. IgA vasculitis in adults is typically lim-   (usually hyperpigmentation) and an increase in local tem-
ited to the skin [29]. However, all patients should be moni-       perature [36]. Extragenital involvement is seen in 6%-20%
tored for long-term systemic involvement [28,30].                  of lichen sclerosus patients [37]. The inner thighs [38] and
    To distinguish between autoimmune bullous diseases,            submammary region [37,38] are frequently affected. Circum-
histopathological, direct and indirect immunofluorescence          scribed plaques or clustered guttate lesions are distinguished
methods are used in addition to clinical features [31]. Pem-       by pale atrophic skin and follicular plugging [37]. It is worth
phigus vulgaris is distinguished by flaccid bullae and painful     remembering that these two diseases share a common patho-
mucosal and skin erosions, as well as a positive Nikolsky sign     genetic basis and can coexist in the same patient [39].
[32]. Although the Nikolsky sign is also positive in pemphi-          Although the diagnosis of viral warts is usually straight-
gus foliaceus, mucosal lesions are uncommon. Small flaccid         forward, slowly growing large exophytic lesions with a pap-
bullae are occasionally encountered, but crusts and erosions       illomatous or verrucous surface and a tendency to compress
are more common [31]. Bullous pemphigoid, on the other             deep tissues should be considered for verrucous carcinoma,
hand, is characterized by tense bullae that develop after ex-      a subtype of squamous cell carcinoma [40]. These lesions
tremely itchy erythematous urticarial patches and plaques          are more common in older men and can be found in the oral
that can last for weeks to months, with mucosal involvement        mucosa, anogenital region, or plantar region [40,41]. The
ranging from 10% to 30% [31,32].                                   presence of verruca vulgaris in a high number of pathology
    Finally, contact dermatitis is a great imitator, presenting    reports could also be explained by therapeutically excised
with erythematous or purpuric patches, edematous plaques,          samples being submitted for legal reasons.
vesicles, bullas, crusts, papules, scales, lichenification, and       Dermatophytosis infections can change clinically as a re-
other lesions [33,34]. Despite its origins as a spongiotic dis-    sult of drug use, particularly topical corticosteroids, and can
ease, it is frequently used as a differential diagnosis in our     be confused with other papulosquamous diseases. Although



8                                                                      Original Article | Dermatol Pract Concept. 2022;12(4):e2022186
dermatophytoses can be diagnosed through direct examina-                One significant limitation of this study is that the results
tion and culture of skin samples, the low sensitivity [42] may      are dependent on a variety of factors such as the study’s time
have necessitated a second pathology opinion.                       period and location, the practice habits of the participating
    The   importance      of   clinicopathological    correlation   physicians, and the available patient population. Another
has been highlighted in a number of studies in the litera-          major limitation is the difficulty in classifying diseases both
ture. According to a study on inflammatory skin diseases,           dermatologically and pathologically. To address this lim-
pathologists could only diagnose 55% of cases based on a            itation, we took a broader approach, excluding variations
histopathological examination alone, but when given clini-          and subtypes of the same diseases in order to represent cases
cal information, they could diagnose 78% of cases correctly         across a broader spectrum.
[43]. Another study found that in 78% of cases, the correct             The study’s strengths include the fact that it was carried
diagnosis was already included in the clinician’s pathology         out with a large number of cases over a 4-year period in a
requisition form [44]. A 5-year study in Tanzania looked at         dermatopathology referral center, and that when new find-
the case distribution and found a similar diagnostic spec-          ings are obtained, they are thoroughly discussed over weekly
trum, with the exception of the relatively high number of           meetings to ensure strong clinicopathological correlation.
Kaposi’s sarcoma and leprosy cases [45]. In addition to these       The rate of non-diagnostic cases remained stable through-
two diseases, a similar study in Ethiopia reported high rates       out the COVID-19 year, as clinicopathological correlation
of cutaneous tuberculosis and leishmaniasis [46].                   of cases was continued through online channels rather than
    The total number of pathology reports was reduced by            weekly meetings.
77.4% as a result of the shift in clinical decision making to           A trained eye and open mind is essential in the diagno-
balance patient care and prevent viral transmission. The bi-        sis of skin diseases, but additional investigations may be re-
opsy rate for clinically benign presentations was reduced,          quired for some challenging cases. While histopathological
and others were prioritized in order to rule out malignancy.        techniques are extremely useful, it should be noted that they,
Despite a decrease in the overall number of cases, the rate of      too, have limitations and cannot always produce a definitive
pathology reports diagnosing keratinocytic and melanocytic          diagnosis alone. Maintaining clinicopathological correlation
neoplasms increased, while the rate of spongiotic diseases de-      and continuous communication between dermatologist and
creased. The frequency of reports involving neoplasms other         pathologist, in our experience, can increase the likelihood of
than keratinocytic and melanocytic cells has also decreased.        reaching a diagnosis by up to 75.3%.
    Following the pandemic, the total number of patients ap-
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Original Article | Dermatol Pract Concept. 2022;12(4):e2022186                                                                             11
