10.5826/dpc.1304a254
text/xml
2160-9381
2929
en
Minoru Hasegawa
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
chemoradiation therapy dermoscopy
An Aggressive Case Of Infundibulocystic Squamous Cell Carcinoma On The Upper Lip: A Hybrid Pathology Of Well-Differentiated And Infiltrative Variants
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-10-31
2022-10-31
2023-10-31
2024-01-16
e2023254
Dermatol Pract Concept
Minoru Hasegawa
2023/10/31
10.5826/dpc.1304a254
e2023254
Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
2160-9381
chemoradiation therapy dermoscopy
en
e2023254
Kossard S. Keratoacanthoma, committed stem cells and neoplastic aberrant infundibulogenesis integral to formulating a conceptual model for an infundibulocystic pathway to squamous cell carcinoma. J Cutan Pathol. 2021; 48: 184-91.
An Aggressive Case Of Infundibulocystic Squamous Cell Carcinoma On The Upper Lip: A Hybrid Pathology Of Well-Differentiated And Infiltrative Variants
https://dpcj.org/index.php/dpc/article/download/2929/2358
             An Aggressive Case of Infundibulocystic
           Squamous Cell Carcinoma on the Upper Lip:
            A Hybrid Pathology of Well-Differentiated
                     and Infiltrative Variants
         Takumi Hasegawa1, Shiro Iino1, Shiori Sekine1, Kohei Kitakaze1, Natsuki Baba1,
                           Noritaka Oyama1, Minoru Hasegawa1


1 Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan



Key words: squamous cell carcinoma, follicular differentiation, immunohistochemistry, chemoradiation therapy dermoscopy
Citation: Hasegawa T, Iino S, Sekine S, et al. An Aggressive Case Of Infundibulocystic Squamous Cell Carcinoma On The Upper Lip:
A Hybrid Pathology Of Well-Differentiated And Infiltrative Variants. Dermatol Pract Concept. 2023;13(4):e2023254. DOI: https://doi
.org/10.5826/dpc.1304a254
Accepted: May 18, 2023; Published: October 2023
Copyright: ©2023 Hasegawa 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: Noritaka Oyama, MD and PhD, Division of Medicine, Faculty of Medical Sciences, University of Fukui, 23-3
Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan. Tel: +81-776-61-8367, Fax: +81-776-61-8112, E-mail: norider@u-fukui.ac.jp




Introduction                                                             Case Presentation
Infundibulocystic squamous cell carcinoma (icSCC) is a                   An 82-year-old Japanese man presented with a month-­
rare skin adnexal neoplasm, originating from the infun-                  history of a small nodule on the upper lip, which rapidly
dibulum of hair follicles. Histologically, it displays follic-           enlarged after diagnostic skin biopsy. Examination revealed
ular differentiation and comprises three distinct variants;              a 3 × 2 cm, reddish indurative plaque with keratotic surface
well-­differentiated, less-differentiated, and infiltrative forms        on the upper lip (Figure 1A). Dermoscopy revealed reddish
[1,2]. The highly differentiated pathology of icSCC may hold             homogeneous area with tiny white cystic structures, resem-
mild-to-moderate phenotype, but often possesses aggressive               bling milia-like cysts (Figure 1B). Previous histological find-
clinical presentation, alerting a prognostic and therapeutic             ings showed a keratin-filled cystic structure with irregular
perspective. We describe for the first time such a case of icSCC         shaped, epithelial walls that invaded into the deep dermis,
with a hybrid histology of well-differentiated and infiltrative          suggesting well-differentiated SCC, although the diagnosis
variants, whose clinical course showed an aggressive behav-              of keratoacanthoma remains likely (Figure 2A).
ior but prompt regression to a concurrent chemoradiation                      He underwent excisional biopsy with safety margin for
therapy, possibly retaining reminiscent of hair cycle.                   the conclusive diagnosis. Histology revealed a volcano-like




Research Letter | Dermatol Pract Concept. 2023;13(4):e2023254                                                                         1
                    Figure 1. Time-course clinical view and dermoscopic findings.
                    (A) A 3 cm × 2 cm, reddish indurative plaque with whitish keratotic surface on the upper lip.
                    (B)	A reddish homogeneous area with scattered tiny white cystic structures, similar to
                         ­millia-like cysts.
                    (C)	Three weeks after marginal resection of the tumor, a local recurrence developed and ­rapidly
                          enlarged, covering almost the entire upper lip and part of the nostril.
                    (D)	The tumor size and invasiveness were dramatically reduced and disappeared leaving a well-
                          healed scar by four courses of chemotherapy with docetaxel and irradiation.



opening of the central keratin-filled plug invaginated by epi-        Enhanced CT scanning showed no evidence of metastasis.
dermal lipping that arose from the follicular infundibulum            Considering the aggressive clinical activity, age, and affected
(Figure 2, B and C), similar to those of keratoacanthoma. The         skin sites, we employed a combined chemoradiation ther-
neighboring epidermis was irregularly thickened with various          apy with docetaxel (25mg/m2 monthly) and electron beam,
sized nests and endophytic infundibular cysts, invading into          achieved a dramatic reduction and completed disappearance
the deep dermis and peripheral nerve sheath (Figure 2, D-             leaving a well-healed scar (Figure 1D).
G). The tumour nests were mostly consisted of eosinophilic
glassy-pale keratinocytes with slight-to-moderate nuclear
                                                                      Conclusions
atypia (Figure 2H). The former histopathology was compat-
ible with well-differentiated icSCC and the latter was infil-         To date, there have been only 5 case reports of icSCC, in-
trative one. Immunohistochemistry showed intense staining             cluding ours (Table 1) [2,4,5]. Their affected skin sites were
of CK16 (Figure 2I) and β-catenin (Figure 2J), follicular in-         the exposed area. Recurrence or metastasis were unclearly
fundibulum markers [2], and Bcl-xL (Figure 2K), a candidate           stated. Our case displayed abrupt local recurrence within
biomarker for distinguishing SCC from keratoacanthoma [3].            3-weeks after complete resection and rapid regression during
    Three-weeks after resection, a local recurrence of the            chemoradiation therapy. The bipolar clinical course may in
tumour developed and rapidly enlarged, which covered al-              part reflect a possible transition of two key life-stages of the
most the entire upper lip and part of the nostril (Figure 1C).        hair follicle (eg, anagen and catagen).



2                                                                          Research Letter | Dermatol Pract Concept. 2023;13(4):e2023254
           Figure 2. Histopathological features (hematoxylin-eosin and immunohistopathological staining).
           (A)	A punch biopsy pathology showing a keratin-filled cystic structure with irregular shaped, epithelial walls that
                invaded into the deep dermis (original magnification, x20).
           (B)	A volcano-like opening of the central keratin-filled plug invaginated by a thinner epidermal lipping architecture
                similar to that of keratoacanthoma (x20).
           (C) Tumor nests and infundibular cysts arose from the follicular infundibulum (x40).
           (D)	Numerous micro- or dilated infundibular cysts of various shapes that infiltrated into the deep dermis (x40).
           (E)	Irregularly and asymmetrically thickening of the epidermis with various sized neoplastic cords or nests from the
                wall of the follicular infundibulum throughout the dermis (x40).
           (F and G) The tumor nests invaded into the deep dermis (x100) and peripheral nerve sheath (x200), respectively.
           (H)	The nests were mostly consisted of eosinophilic glassy and pale keratinocytes with slight to moderate nuclear
                atypia (x200).
           (I)	Broad and intense expression of CK16 in the deeply situated neoplastic components (x100).
           (J)	Membrane-dominated staining of b-catenin with jigsaw-like nuclear/cytoplasmic pattern in the whole neoplas-
                tic c­ omponents (x100).
           (K) Cytoplasmic staining of antiapoptotic protein Bcl-xL was observed in the nest (x100).



   An infundibulocystic biology towards carcinogenic tran-                  The overall prognosis and definitive diagnosis of icSCC
sition proposes the involvement of two major molecular cas-             remain inconclusive. The aggressive clinical behavior in our
cades, namely oncogenic RAS and Wnt/β-catenin pathways [6].             case may be attributed to a rare pathological hybrid pos-
An imbalance of two signaling pathways may affect the stability         sessing well-differentiated and infiltrative characters, with
of hair infundibulum regeneration, responsible for the carcino-         direct activation of the oncogenic Wnt signaling pathway by
genic state and possibly aggressive clinical behavior in our case.      β-catenin overexpression.



Research Letter | Dermatol Pract Concept. 2023;13(4):e2023254                                                                       3
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                                                                                                   Table 1. Summary of infundibulocystic squamous cell carcinoma a thus far reported in the literature.
                                                                                                    Age/                      Size                                      Local
                                                                     Case        Authors            Sex          Site         (cm)          Treatment                recurrence           Metastasis           Clinical features          Follow-up (yr)   References
                                                                 1           Misago N, et al       79/M       Upper lip        3       N.D.                      None                  None                   Erythematous                     1.5             2
                                                                                                                                                                                                              keratotic plaque
                                                                 2           Misago N, et al       56/M       Upper lip       2.5      N.D.                      None                  None                   Erythematous                      2              2
                                                                                                                                                                                                              keratotic plaque
                                                                 3           Kim SM, et al         67/M       Posterior        2       Excicion                  N.D.                  None                   Flat nodule,                    N.D.             4
                                                                                                              ear                                                                                             keratotic plaque
                                                                 4           Suma A, et al         72/M       Left helix       2       Excicion and              None                  None                   Solitary, crusted,               3.5             5
                                                                                                              of ear                   postoperative                                                          flesh-colored,
                                                                                                                                       external beam                                                          rubbey mass
                                                                                                                                       radiotherapy
                                                                 5           Our case              82/M       Upper lip        3       Marginal resection,       +                     None                   Reddish indurative                1          this report
                                                                                                                                       chemoradiation                                                         plaque with a
                                                                                                                                       therapy                                                                whitish keratotic
                                                                                                                                                                                                              surface
                                                                N.D., not described.

                                                                To date, there have been only 5 case reports of icSCC, including ours. Their affected skin sites were the exposed area. Recurrence or metastasis were unclearly stated.




Research Letter | Dermatol Pract Concept. 2023;13(4):e2023254
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Research Letter | Dermatol Pract Concept. 2023;13(4):e2023254                                                                                 5
