Mohs Micrographic Surgery in the Setting of Squamoid Eccrine Ductal Carcinoma: Addressing a Diagnostic and Therapeutic Challenge

Shane Clark, MD, Department of Internal Medicine, Division of Dermatology, The Ohio State University Medical Center, Columbus, Ohio; Adam Young, BS, The Ohio State University College of Medicine, Columbus, Ohio; Eli Piatigorsky, MD, Department of Internal Medicine, Division of Dermatology, Nova Southeastern University College of Osteopathic Medicine, Ft. Lauderdale, Florida; Larisa Ravitskiy, MD, Department of Internal Medicine, Division of Dermatology, The Ohio State University
Medical Center and Ohio Skin Cancer Institute, Columbus, Ohio

Disclosure: The authors report no relevant conflicts of interest.

Objective: The purpose of this case report and literature review was to summarize the current knowledge surrounding this rare cutaneous tumor and promote awareness of the success of Mohs micrographic surgery as a definitive therapeutic modality in a case of squamoid eccrine ductal carcinoma. Design: Case report and literature review. Setting: Squamoid eccrine ductal carcinoma has been introduced as a rare type of eccrine carcinoma with only eight previously reported cases in the literature. Despite the tumor’s introduction as a type of eccrine carcinoma, the true etiology is currently contentious; the lesion represents a diagnostic challenge, and its malignant potential remains uncertain. Thus, proper histological diagnosis and definitive management are under active discussion. Participants: Index case patient records review and peer-reviewed literature. Results: The authors present the ninth reported case of squamoid eccrine ductal carcinoma and the third report of Mohs micrographic surgery for complete extirpation of the lesion. Conclusion: The anecdotal success of Mohs micrographic surgery as a therapeutic modality in the treatment of three cases of squamoid eccrine ductal carcinoma (including the case reported herein) suggests that this is an effective yet tissue-sparing surgical modality. However, given the poorly understood natural history of squamoid eccrine ductal carcinoma and the uncertainty of the lesion’s etiological and malignant taxonomy, further experiences with this tumor are necessary and close follow up of patients is suggested.  (J Clin Aesthet Dermatol. 2013;6(4):33–36.)

Sweat gland carcinomas are uncommon cutaneous lesions demonstrating nonuniform histological features, behavior, and nomenclature.[1,2] Eccrine carcinoma (EC) is the most common subtype of adnexal carcinoma representing 0.01 percent of all cutaneous tumors. EC is often observed clinically as a slow-growing nodular plaque on the scalp, extremities, or trunk of middle-aged or elderly individuals.[3] Squamoid eccrine ductal carcinoma (SEDC) has been introduced as an exceedingly rare type of EC with only eight previously reported cases in the literature.[1,2,4–7] This lesion’s etiology is currently controversial as it may represent squamous cell carcinoma (SCC) arising from eccrine ducts, a subtype of EC with extensive squamoid differentiation, or a biphenotypic carcinoma.[8] Histologically, SEDC is observed to be poorly circumscribed with an infiltrative growth pattern and deep extension into the dermis and subcutaneous tissue, characterized by prominent squamous epithelial proliferation superficially with cellular atypia, keratinous cyst formation, squamous eddies, and areas demonstrating eccrine ductal differentiation.[5,8]

Given the lesion’s indeterminate malignant potential, attention has been directed toward the pitfalls of definitive histological diagnosis and the most effective potential treatment to minimize the risk of recurrence or metastasis. Squamous differentiation, at times dominating the histological picture, may result in misdiagnosis of the tumor as SCC.[1,6] Mohs micrographic surgery (MMS) has been established as a successful method for the surgical removal of a variety of cutaneous malignancies including basal cell carcinoma and SCC.[5,9] Likewise, MMS has been proven superior to conventional excision in the treatment of ECs: Local recurrence has been reported to be 10 to 70 percent after conventional excision and 0 to 5 percent after MMS at an average of 30.9 months follow up.[5,10] Most relevant to the discussion herein, MMS has been successful in the definitive treatment of two previously reported cases of SEDC.[2,5] The authors present the ninth case of SEDC in the literature and third report of MMS for complete extirpation of this rare malignancy.

Case Report
A 75-year-old man presented for evaluation of a 1.6mm pink, indurated plaque on the left clavicle of 5.5 months duration. There was no bleeding or ulceration of the lesion. The patient had a history of stage II chronic lymphocytic leukemia diagnosed 18 years prior to presentation, which had been in remission for 10 years. He had a history of nonmelanoma skin cancers including SCC and basosquamous carcinoma. The patient was otherwise healthy at presentation. On the initial shave biopsy, morphological features of adnexal differentiation and immunohistochemistry (IHC) staining characteristics raised the possibility of an EC, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), SEDC, other carcinoma with eccrine differentiation, or SCC involving ductal structures. The IHC profile included positivity for cytokeratin (CK) 34, CK5/6, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA), and negativity for CK7, CK20, and Ber-EP4.

Given the wide histological differential and the superficial nature of the original biopsy, tissue from debulking performed prior to MMS was sent for permanent sections to obtain a definitive diagnosis. This specimen exhibited features of a deeply infiltrative neoplasm with both prominent squamoid and focal eccrine ductal differentiations (Figure 1). Rare nests in the upper portion of the lesion showed duct-like structures. There was underlying dermal sclerosis with descent into the dermis and solar elastosis in the adjacent dermis. The IHC profile of the biopsy and debulking specimen consistently demonstrated positive staining of epidermal and dermal eccrine ducts within the dermis with CEA, which highlights luminal epithelium (Figure 2). EMA, which stains apocrine/ eccrine/sebaceous epithelium and tumors as well as primary cutaneous and metastatic carcinomas, was positive in some of the upper squamoid nests (Figure 3). Tumor cells were also positive for p63. CK5/6 showed positive staining in the epidermis as tumor nests—SCC is typically positive for CK5/6, but positivity is also common in cutaneous adnexal neoplasms.[11] There was no significant staining with CK20 (often positive in metastatic colon, genitourinary, and pancreatic/biliary cancer as well as Merkel cell carcinoma, but not sweat gland tumors), CK7 (often positive in sweat gland tumors, but rarely positive in SCC), or Ber-EP4 (positive in SCC, but negative in sweat gland tumors).[11]

The tumor was cleared with MMS in three stages resulting in a 3.1.x3.3cm defect. At 12 months follow up, the patient was free of locoregional or distal metastases.

SEDC is a rare entity in the literature, with this case representing only the ninth reported incidence and the third demonstrating use of MMS in definitive treatment. The malignant potential and etiological classification of this tumor remains controversial. Historically, a diagnosis of SEDC was based on a combination of critical morphological and IHC features. The lesion has consistently presented clinically as a solitary nodule on the head, neck, or extremities. Histologically, it is a poorly circumscribed, infiltrative lesion composed of atypical squamoid cells forming squamous eddies, horn cysts, and occasional prominent keratinization superficially, while the deeper components are arranged in small, infiltrative nests and cords of atypical keratinocytes demonstrating ductal structure analogous to microcystic adnexal carcinoma (MAC) or EC.[8] The differential diagnosis for SEDC includes SCC, metastatic carcinoma with squamoid features, and eccrine tumors including eccrine poroma, MAC, and porocarcinoma with squamous differentiation.[2,3,12–14] The IHC profile of eccrine neoplasms includes positivity for S-100, EMA, CKs, and CEA.[8] Positive staining with EMA and CEA is typical of glandular tissue and is supportive of an adnexal origin as the aforementioned markers are typically negative in epithelial malignancies such as SCC.[2] IHC has additional utility in demonstrating the combination of p63 and CK5/6 positivity in order to delineate primary from metastatic adenocarcinoma in the skin.15,16 The case herein  demonstrated positive staining for both p63 and CK5/6, supporting a primary cutaneous malignancy rather than metastatic disease.

SEDC was first mentioned by Wick and Swanson[3] as a subtype of EC with prominent squamoid differentiation, which poses a potential diagnostic pitfall as it can be easily misdiagnosed as SCC. In Chhibber et al,[6] SEDC was thrice misdiagnosed as SCC on biopsy by multiple dermatopathologists. The often super?cial nature of initial biopsies was likely a contributing factor to this diagnostic challenge.[2] The significance of the diagnostic dilemma lies in the disparity of clinical behavior between SCC and eccrine cancers. Eccrine adnexal tumors are characterized by multiple local recurrences (70–80% of cases), perineural invasion, and even metastasis—approximately 50 percent of the time—to regional lymph nodes and viscera: lungs, liver, bones, and brain.[3,17] SCC has a recurrence rate of 3.1 to 18.7 percent (depending on location and treatment modality) at five or more years and a rate of metastasis that ranges from 5.2 to 37.8 percent depending again on tumor location.[18] In those cases of SEDC thus far reported that were not lost to follow up, none metastasized while one patient experienced two episodes of recurrence after conventional excision.[1,2,5,6,7] Moreover, there have been three cases that demonstrated perineural and/or perivascular invasion.[1,6] Therefore, despite SEDC having been largely classified as an eccrine tumor, the literature suggests its behavior is less aggressive, although this conclusion is tempered by the dearth of cases thus reported. However, given SEDC’s pathologically demonstrated invasive potential, recurrence rate, and ambiguous metastatic potential, it is important for physicians to be aware of barriers to proper diagnosis as well as the surgical modalities best suited to the effective management of this lesion.

Due to its relative rarity, there have been no randomized studies comparing treatment modalities or surgical margins utilized in MMS or other surgical treatments of SEDC. Thus, given the limited data regarding effective treatment of SEDC coupled with its demonstrated ability for recurrence and perineural and perivascular invasion, it may be appropriate to reference the treatment of lesions to which SEDC may be most closely related based on its histological features and behavior: EC and SCC. For definitive treatment of ECs, surgical extirpation with complete margin examination is recommended as the lesion tends to be underestimated in its size, is aggressive in its infiltration, and has a proclivity for perineural and perivascular invasion.[6] Moreover, MMS has been proven to have lower recurrence rates than other treatment modalities, reporting a five-year recurrence rate of 3.1 to 5 percent for primary SCC.[18,19] The recurrence rates of ECs have also been reported to be higher with surgical excision (10–70%) versus MMS (0–5%) at an average 30.9 months follow up.[5] Thus, the literature suggests wide-excision margins (4–5mm) to be utilized in the treatment of EC, but Kim et al[5] were successful utilizing a narrow margin (2mm) for SEDC, with the significant squamous component guiding precise, complete excision. The evident success of MMS as a therapeutic modality in the treatment of three cases of SEDC (including the case reported herein) suggests that this is an effective yet tissue-sparing surgical modality. However, given the poorly understood clinical progression of SEDC and the uncertainty of the lesion’s etiological and malignant taxonomy, further experiences with this tumor are necessary and close follow up of patients is suggested.

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