Primary cutaneous cribriform tumor in uncommon locations

Dear Editor, The primary cutaneous cribriform tumor (PCCT), previously known as primary cutaneous cribriform apocrine carcinoma, has been renamed in the latest WHO classification of skin tumors.[1] It is a rare, low-grade, and indolent neoplasm of sweat glands. Unlike apocrine carcinoma, which usually arises in areas rich in apocrine glands, particularly the axilla, PCCT most commonly occurs on the extremities, comprising 77% of reported cases. We herein present the two cases of PCCT in atypical locations: the back and the chest. A 58-year-old female presented with an asymptomatic, firm nodule on her left back of unknown duration [Figure 1e]. Total excision revealed an unencapsulated, nodular dermal tumor, composed of cribriform and tubular structures, with lymphocyte infiltration at the periphery [Figure 1a]. The tumor cells had moderately pleomorphic nuclei and eosinophilic cytoplasm. Mitotic figures were rare, and there was no evidence of perineural or lymphovascular invasion [Figure 1b]. Immunohistochemical studies showed that the tumor cells expressed CK7 and focal S-100 but were negative for paired box gene 8, TTF-1, CD117, CK20, estrogen receptor/progesterone receptor, p63, and smooth muscle actin (SMA) [Figure 1c and d]. Cutaneous cribriform tumor was suspected. A whole-body computed tomography (CT) scan showed no evidence of internal malignancy, supporting the diagnosis of PCCT.Figure 1: (a) An unencapsulated dermal tumor with lymphocyte aggregation at the periphery (H and E, ×40) (b) Higher magnification shows a cribriform pattern of the tumor cells and varying sizes of cystic spaces (H and E, ×100) (c) Immunohistochemical study: The tumor cells are immunoreactive for cytokeratin 7 (×100) (d) The tumor cells are immunoreactive for S-100 (×100) (e) A 2 cm × 1.5 cm dermal nodule on the back.A 74-year-old male with underlying diabetes mellitus, dyslipidemia, and chronic kidney disease presented with a cyst on his chest for 6 months [Figure 2a]. Histological examination revealed a well-circumscribed dermal tumor composed of nests of epithelial cells, exhibiting a cribriform pattern with areas of solid growth, cystic spaces, and occasional thin intraluminal bridging strands and intraluminal micropapillary projection [Figure 2b and c]. Immunohistochemical studies showed epithelial membrane antigen (EMA) expression and negativity for SMA, gross cystic disease fluid protein 15 (GCDFP-15), and TTF-1. Additional tumor marker tests and a whole-body CT scan showed no signs of malignancy, confirming the diagnosis of PCCT. He underwent a wider excision with a 1 cm clinical margin, which revealed no residual carcinoma histologically and was followed up for 4 years with no recurrence.Figure 2: (a) A 0.5 cm × 0.5 cm cyst on the chest (b) Cystic spaces with intraluminal bridging strands (H and E, ×400) (c) A well-circumscribed dermal tumor with epithelial nests showing a cribriform pattern (H and E, ×40).PCCT is a rare cutaneous adnexal neoplasm, with fewer than 100 cases documented. It is more prevalent in females, with a ratio of 2:1 and typically occurs in middle-aged adults, with an average age of 46.5 years (ranging from 20 to 77). PCCT is commonly located in extremities (77%), followed by the trunk (12%) and the head/neck region (11%) [Supplementary Table 1]. The tumor usually manifests as a slowly enlarging nodule, often initially misdiagnosed as epidermal cyst or dermatofibroma. The diagnosis is primarily based on histopathological examination, which reveals a well-circumscribed, unencapsulated dermal nodule without epidermal attachment and occasional lymphoid aggregates at the periphery.[2] It comprises interconnected nests of epithelial cells forming a distinctive diffuse cribriform pattern, sometimes intermixed with the areas of solid growth. The tumor cells have pleomorphic, hyperchromatic nuclei with eosinophilic cytoplasm, and the cystic spaces vary in size and shape. Apocrine differentiation is indicated by decapitation secretion at the luminal borders of some tubules.[3-5] Immunohistochemical studies for PCCT typically show positivity for CK AE1/AE3, Cam 5.2, and CK 7. CEA and EMA may be positive in some cases, suggesting luminal differentiation. Positivity for S100 is variable. SMA and p63 are negative, indicating the absence of a surrounding myoepithelial cell layer.[3-6] No immunohistochemical panel can fully differentiate between primary cribriform carcinoma and cutaneous metastasis from visceral malignancies with cribriform patterns. Additional imaging and clinical history are needed to rule out metastasis, although certain immunohistochemical studies can provide support. For example, breast carcinoma may present with GATA3 and GCDFP-15 positivity while CK20 positivity could be seen in some metastatic tumors (e.g., from the gastrointestinal tract or urothelium) that may present with cribriform patterns.[3,4,6]Supplementary Table 1: Summary of the reported case in the literatureImportant histological differential diagnoses include tumors that can exhibit a cribriform pattern, such as primary cutaneous adenoid cystic carcinoma (PCACC), primary cutaneous secretory carcinoma (PCSC), and tubular adenoma (TA). PCACC most commonly appears in the head-and-neck area. It often recurs locally and has the potential to metastasize. The tumor cells are generally uniform in size and shape, with monomorphic nuclei and distinct basement membrane deposition, highlighted by PAS staining. Frequent perineural invasion helps distinguish it from PCCT.[2,3,5] PCSC typically has a less well-circumscribed border, with more eosinophilic or amphophilic intraluminal secretion and the tumor cells may exhibit vacuolated cytoplasm.[2,7] TA can mimic PCCT due to its dilated cystic spaces, intraluminal bridging, and micropapillary projections. However, it is characterized by a preserved myoepithelial cell layer, a relatively paucicellular fibrous stroma, and tumor cells that lack cytologic atypia.[5,7] Overall, PCCT has a favorable prognosis, with no reported recurrences or metastases following complete excision. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are publicly available. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.