Case 1 A 51-year-old man presented with a pruritic erythema on the right waist for over 5 years. In the past years, he paid no attention to it, though a dull red nodule had developed and gradually enlarged on the erythema. Physical examination revealed a 5 cm × 3 cm oval-invasive erythema covering with some scale, in the center of which a dull red, solid, non-tendor, well-demarcated nodule measuring 3 cm × 2 cm × 2 cm protruded from the skin surface. Significant hyperplasia of dilated capillaries, and a few scales can be seen on the surface of the neoplasm (Fig. 1a). Thoracoabdominal CT revealed no significant abnormalities, and peripheral blood count and tumor marker tests were normal.

Case 2 An 87-year-old female presented with an asymptomatic neoplasm on the right maindibular angle for over a year. Physical examination showed a dull red patch measuring 2 cm × 1.5 cm , with a solid, well-defined and protruding nodule in the center measuring  1.5 cm × 1.5 cm × 1 cm, and with some scaling (Fig. 1b). There were no positive findings by the cranial and thoracoabdominal CT scans.

Biopsies were performed respectively on the neoplasms in both cases. Both the histopathological examination of the two cases revealed gross hyperkeratosis with parakeratosis overlying a thickened dysplastic epidermis, with the atypical mitoses and multinucleated tumor giant cells. A small blue cell tumor extended deeply into the subcutaneous fat under the low-power magnification, and the pathognomonic tumor nuclei were large and pale staining and contain tiny nucleoli (Fig. 2a–f). Immunohistochemistry of case one showed positivity for CK, CK20, EMA, Synaptophysin (Syn) and Bcl-2 (Fig. 3a–d). Vimentin was positive in the stroma, while CD3, CD4, CD8 and CD20 showed scattered positivity. Ki67 was positive in 90% of tumor cells. LCA, CD68, CD30, TdT, CD56, Mum-1, TIA1, Granzyme B, EBER, Neuron-Specific Enolase (NSE), Chromogranin A (CgA) and CD79a were negative. In case two, immunohistochemistry showed positivity for CD56, focal positivity for CK, CK20, CAM5.2 and CgA, and negativity for Syn and CK7. Ki67 was positive in 80% of cells (Fig. 4a–f)

Clinical aspect of an MCC overlapping BD. a Solitary and dome shaped reddish nodule surrounded by an erythematous scaly patch on the right waist. b Ovoid dark erythematous painless tumor mass on the right mandibular angle, with peeling and scabbing on the surface of the mass

a, b On histopathology, BD is juxtaposed or strictly intermingled with MCC (H&E, ×4). c, d BD shows full thickness of atypical squamous cells (H&E, ×10). e, f Dermal dense infiltration of small round hyperchromatic small cells (H&E, ×10)

a–c Immunohistochemical staining showed that CK, CK20 and Syn were positive Magnification: ×10. d Immunohistochemical staining showed that Ki67 was positive in 90% of the cells Magnification: ×10

a Immunohistochemical staining showed CD56 positive Magnification: ×10. b–e Immunohistochemical staining showed that CK, CK20, CAM5.2 and CgA were focally positive Magnification: ×10. f Immunohistochemical staining showed that Ki67 was positive in 80% of the cells Magnification: ×10

Both patients were diagnosed with MCC overlapping BD. They all underwent surgical excision extending 1 cm beyond the tumor margins. There was no recurrence during a follow-up period of 3 years in case one and about half a year in case two.

In the last 11 years (from 2013 to 2023), only 13 cases (including our two cases) of MCC overlapping BD have been described in the literature. The incidence was slightly higher in females than in males, with a male-to-female ratio of 1:1.6 (5 cases to 8 cases). The age ranged from 32 to 87 years (mean 72 years, median 73 years). Lesions mainly occurred at the age of more than 70 years (77%), and only one extremely rare case occurred at the age of 32 years. The overall duration of the disease varied from 2 months to 5 years. Some patients had a history of annual herbal pill consumption, exposure to ultraviolet radiation, and previous diagnoses of multiple myeloma, basal cell carcinoma, and BD (Choe et al. 2014; Miraflor et al. 2016) (Table 1).

All the studies reported the location of the lesions. MCC overlapping BD were mostly located on the faces (N = 7/13, 53.8%), followed by the trunk (N = 3/13,23.1%), the upper extremity (N = 1/ 13,7.7%) , lower extremity (N = 1/ 13,7.7%) and groin (N = 1/ 13,7.7%). No patient had multiple lesions (Table 1).

Information regarding the initial clinical presentation was available for all patients. The lesions were most frequently described as asymptomatic, firm, dull red nodules on red or dark brown patches with frequent rapidly growing behavior, or as solitary nodules. None of the lesions described with accuracy were correctly diagnosed before biopsy and histological examination. The size of the tumor lesions was available for 11 lesions (84.6%). Tumor diameters ranged from 0.3 to 6.5 cm (mean: 2 cm, median: 1 cm). Rapid growth, either of new lesion or stable lesion from several months was the most frequent motivation for biopsy and diagnosis (Table 1).

Locoregional or distant metastases occurred in four patients (30.8%) (Swain et al. 2022; Choe et al. 2014; Ishida et al. 2013; Kiyohara et al. 2019). One patient showed lymph node and liver metastasis (Choe et al. 2014). After local excision of the cutaneous lesion and left inguinal lymph node dissection in one patient, several dermal and subcutaneous nodules developed successively on the left lower extremity (Kiyohara et al. 2019) (Table 1).

All 13cases had a histological diagnosis of MCC overlapping BD (Table 1). Eight patients were diagnosed by histopathology, followed by extensive local excision treatment. Of them, an 82-year-old female was diagnosed with MCC overlapping BD by histopathology but refused further evaluation and operative treatment (Jeong et al. 2018). Seven patients underwent direct extensive local excision treatment, followed by histopathological detection of the tissue post-surgery (Tono et al. 2015; Swain et al. 2022; Choe et al. 2014; Miraflor et al. 2016; Ishida et al. 2013; Kiyohara et al. 2019; Yamamoto 2014; McGowan et al. 2016; Casari et al. 2018). A 77-year-old woman was found to have lymph node and liver metastases after surgical treatment, followed by radiation and chemotherapy (Choe et al. 2014). A 65-year-old Japanese man experienced recurrent skin lesions after local surgery and lymph node clearance. After receiving avelumab treatment for 2 months, all lesions disappeared completely. Subsequent follow-ups over six months showed no recurrence (Kiyohara et al. 2019). A 32-year-old lady underwent surgery, lymph node clearance and received radiation therapy. This patient had an axillary dissection because of a palpable lymph node. Two lymph nodes out of 14 showed metastatic deposits, hence the female patient received radiotherapy after which she is well and completely free of disease now, 7 years after the initial diagnosis (Swain et al. 2022). A 71-year-old Caucasian male remained recurrence-free during the 1-year follow-up after surgical treatment (Miraflor et al. 2016). The follow-up status for the remaining seven patients has not been reported.

Histopathologically MCC primarily locates within the dermis and can invade subcutaneous tissues. At low magnification, it appeared as a typical small round blue-cell tumor, comprising three different histologic subtypes: trabecular type, intermediate type and small cell type. Among them, the intermediate type was the most common. The tumor consisted of nodules and diffuse sheets of basophilic tumor cells with vacuolated, pale-staining nuclei containing small nucleoli. The cytoplasm was indistinct with common nuclear folding. The trabecular type, the least common, was composed of slender, uniformly shaped cells, often with nuclear folding. The small cells type was characterized by infiltrates of deeply staining 'oat cell-like' cells with significant cell fragmentation.

The histopathological feature of MCC overlapping BD include abnormal keratin-forming cells of BD within the epidermis and small round blue-staining cells of MCC in the dermis. There has been a case reported where the MCC component, in association with BD, was confined to the epidermis, referred to as “intraepidermal MCC”(Miraflor et al. 2016).

The immunohistochemical characteristics of MCC overlapping BD indicate that MCC cells express neuroendocrine markers such as NSE, CK20, Neurofilament (NF), CgA, and Syn. Most MCCs do not express Thyroid Transcription Factor-1 (TTF-1). On the other hand, BD commonly exhibits expression of squamous cell markers like CK5/6, CK10 and CK14.

Dermoscopic examination was only reported in two patients (Casari et al. 2018). Dermoscopic examination showed the presence of clustered dotted vessels over a reddish structureless area that was suggestive for the diagnosis of BD. Addittional dermoscopical characteristic of the nodule included an atypical vascular pattern with tortuous vessels overlying a whitish background.