INTRODUCTION

Basal cell carcinomas (BCCs) are slow-growing, locally aggressive tumors originating from interfollicular epidermis and/or hair follicle (1). It is the most common malignancy in fair skinned populations worldwide and has many histological variants including nodular, superficial, basosquamous, infiltrating etc. (1). Although there is no specific statistical ratio regarding its prevalence in the literature, we know that signet ring cell BCC is a very rare variant of BCC that tumor cells contain large, pink, eosinophilic, eccentric intracytoplasmic inclusions that crescentically compress nuclei to the cell border (2).

CASE PRESENTATION

A 74-year-old man presented with an irregular nodule 2.5x2 cm in size on the left ala of nose for 3 years. The patient was evaluated as fitz patrick type 3 on physical examination. The lesion was diagnosed as BCC by incisional biopsy and than a wide excision was performed.

Histopathological and Immunohistochemical Findings

On light microscopy the tumor consists of islands of basaloid cells with peripheral palisading, clefts separating neoplastic epithelium and intervening fibroblastic stroma (retraction artefact) (Figure 1). Signet ring cell configuration was observed among neoplastic cells focally. The most prominent feature was cells containing large eosinophilic, pink, eccentric intracytoplasmic inclusions, which compress the nuclei in a few lobules (Figure 2A, B, C). The cell inclusions did not stain with  periodic acid schiff (PAS) (Figure 3) and alcian blue pH 2.5 (Figure 4). Tumor cells were positive for Ber-EP4 (Figure 5) but negative for S-100 except for some cells corresponding to Langerhans cells, which are scattered within tumor islands (Figure 6).

DISCUSSION

Although BCC is the most common cutaneous malignancy, signet ring cell BCCs are rare in routine and our case was not a pure signet ring cell variant as well. At this point, the overall pattern of the neoplasm becomes the most important diagnostic criterion for histological evaluation (3). Although the characteristic features are well-known of BCC, pathologists may consider metastasis of an adenocarcinoma when observing signet ring cells in a skin neoplasm. Nuclear pleomorphism, hyperchromatism, mitotic activity, a type of infiltration (e.g. diffuse patern supports metastasis), and clinical correlation could help to distinction between metastasis and BCC (4). In cutaneous metastases of visceral adenocarcinomas, there is nuclear displacement because of cytoplasmic musin deposition, which giving signet ring shape to the cell. Therefore, neoplastic cells are stained with PAS and D-PAS (3). In metastatic lesions, typically there is a diffuse dermal infiltrate. Additionally the overlying epidermis is intact and there is an underlying spared zone of uninvolved dermis which is called grenz zone (5). Also the neoplastic cells are generally positive for carcinoembryonic antigen (3). Primary cutaneous signet ring cell neoplasms can also be seen like trichilemmal carcinoma, signet ring cell lymphoma, signaling ring cell squamous cell carcinoma (SCC), sebaceous carcinoma, signet ring melanoma except for metastatic adenocarcinomas (5). In trichilemmal carcinoma, there are foci of keratinization, PAS-positive tumor cells, lobular architecture composed of large atypical cells with clear cytoplasm and prominent nucleoli. This neoplasm is usually deeply seated with no connection to the epidermis and there is no normal pilar structures (6). In signet ring cell lymphomas, tumor cells may have abundant clear or vacuolated cytoplasm that giving shape to cell signet ring appearance mostly because of the abnormal membrane recycling or secretion of immunoglobulin and either B or T-cell markers are positive immunohistochemically (7,8).

In signet ring cell SCCs are negative for BREP4 and CD10 (9). In sebaceous carcinomas are characterized by lobular formations of sebaceous and undifferentiated basaloid cells. Also, the sebaceous cells show foamy, microvesicular cytoplasm instead of a signet ring shape (6). Sebaceous carcinoma shows immun reactivity for CKPAN, EMA, adiphopilin and perilipin (10). Signet ring melanoma stain for melanocyte markers such as HBM-45, Melan-A, and S-100.

To sum up, signet ring cells are uncharacteristic of any particular primary or secondary cutaneous neoplasm. We attach great importance to histomorphology in the differential diagnosis since BCC has well-known diagnostic criteria such as peripheral palisading, retraction artefact, tumor nests. We report this case due to the limited number of studies in the literature about signet ring cell BCC.

CONCLUSION

This case report and similar studies could make it easier to recognize this tumor. Further studies including more cases would be necessary to clarify the clinical behavior and nature of signaling ring cell BCCs.

Ethics

Informed Consent: Patient consent could not be received from the patient due to the retrospective design of the study.

Peer-review: Internally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: Ö.Y., B.A., S.A.A., Concept: Ö.Y., B.A., S.A.A., Design: Ö.Y., B.A., S.A.A., Data Collection or Processing: Ö.Y., B.A., S.A.A., Analysis or Interpretation: Ö.Y., B.A., S.A.A., Literature Search: Ö.Y., B.A., S.A.A., Writing: Ö.Y., B.A., S.A.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.