Primary cutaneous apocrine carcinoma (PCAC) is a rare malignant tumor originating from adnexal structures, such as sweat glands (1, 2). It is an invasive, locally destructive neoplasm spreading from the reticular dermis to the subcutaneous tissue. Previous reports indicate that it is primarily a malignancy of adults, with no association found with race or sex (3). Although they can develop on any area of the skin, they are more commonly found in regions with a high concentration of apocrine glands, especially the axilla (1). These entities can represent a diagnostical challenge due to clinical variability and lack of consensus on defined histopathological criteria. Moreover, they may display morphological mimicry to other types of cancer with apocrine features, such as breast adenocarcinoma (4). This case study describes an initial misdiagnosis of PCAC as breast cancer, highlights a potentially unique pathoetiological origin, and outlines the subsequent steps leading to the correct diagnosis and appropriate treatment. This report is prepared in accordance with the CARE guidelines.

A 60-year-old Caucasian male presented for excisional biopsy of a painless, solitary axillary nodule with slow progressive growth over several months. He had undergone excision of a histologically confirmed syringoma in the same area years earlier, and the current lesion was initially presumed to be a benign recurrence. The patient had an otherwise unremarkable medical and family history.

Histology revealed fully matured squamous epithelium superficially, with deeper layers showing an infiltrative neoplasm composed of epithelial nests exhibiting cribriform to adenoid architecture and, in deeper regions, areas of solid growth. There was focal infiltration into subcutaneous adipose tissue and perineural sheath involvement. The epithelial clusters were lined by cuboidal cells with a high nuclear-cytoplasmic ratio, prominent nuclear membranes, small nucleoli, and no evidence of keratinization or definitive follicular differentiation. Immunohistochemistry demonstrated nuclear androgen receptor expression (90%) and cytoplasmic positivity for CK7, BerEp4 and EMA. CD117 was negative, as were p40, estrogen receptor (ER) and progesterone receptor (PR). HER2/neu showed a score of 2 +. The lesion was identified as a moderately differentiated apocrine carcinoma, with tumor cells extending to the resection margins.

Based on its immunohistochemical profile, the lesion was initially interpreted as triple-negative breast cancer, potentially arising from accessory mammary tissue due to its localization or representing metastasis. The patient was thus referred to a breast clinic for further evaluation.

Comprehensive imaging in a senological setting, including breast ultrasound and CT imaging of the trunk and abdomen, uncovered a previously unrecognized subcutaneous tumor mass in the left axilla, located deep to the site of excision (Figure 1). A primary lesion within the breast was not detected. A broad range of imaging studies was therefore conducted to rule out other potential internal primary adenoid tumors, with MRI, gastroscopy, colonoscopy and bone scintigraphy showing no evidence thereof.

Given the clinical and histological ambiguity, which resulted in a delay of approximately 8 weeks, the patient was referred to a dermato-oncological clinic for further evaluation and surgical treatment. There, the subcutaneous axillary mass was excised and further histopathological examination was performed.

The resected neoplastic conglomerate measured 6.6 x 5.9 x 3.5 cm and contained two metastatic lymph nodes (Figures 2, 3). Histological examination confirmed negative tumor margins with a minimum clearance of 1.1 cm in all directions. As the prior immunohistochemical HER2 score of 2+ was deemed equivocal, additional analysis using chromogenic in situ hybridization (CISH) was performed to assess HER2 gene amplification, which was negative. Based on histopathological findings, including asymmetric overall architecture, progressively smaller and less dilated ductal structures, and intratumoral perineural invasion, a diagnosis more consistent with a primary tumor than with a cutaneous metastasis of an adenoid carcinoma was supported. A PET-CT scan was additionally conducted, which conclusively ruled out any internal primary disease. The slow progression over several weeks, along with imaging findings, further argued against (metastatic) mammary carcinoma.

After discussion in the tumor board, breast cancer was ruled out, and a diagnosis of primary cutaneous apocrine carcinoma (pT3N1M0, G2) was reached. Although histological margins were clear and no residual disease was detected clinically or radiologically, adjuvant locoregional radiotherapy and close surveillance were initiated following interdisciplinary discussion to manage the risk of regional recurrence. Table 1 summarizes the timeline of clinical events.

The patient was in good health and showed no clinical or radiological evidence of recurrence one year after excision of the axillary node.

The marked histological similarity between PCAC and breast adenocarcinoma often precludes definitive distinction based on microscopic features alone (2, 5). Although CK7 positivity is suggestive of cutaneous apocrine carcinoma, it lacks specificity, as CK7 is widely expressed in various epithelial malignancies, including those of lung and ovary (6). Therefore, CK7 should be interpreted only in combination with additional markers and within the clinical context to avoid misclassification. The absence of estrogen, progesterone and HER2 receptor expression may also argue against a diagnosis of breast cancer, though it does not rule out triple-negative breast carcinoma (2).

Nonspecific markers may be expressed across a wide range of carcinomas and other neoplasms, limiting their value for definitive classification and contributing to diagnostic uncertainty, particularly in poorly differentiated or undifferentiated tumors, where classic morphologic features are absent or equivocal (7, 8). In the absence of pathognomonic immunostains, broad immunohistochemical panels are often required, which can deplete limited tissue samples and still fail to yield a conclusive diagnosis in some cases (9). In addition, technical variables, interpretive subjectivity, and aberrant antigen expression further increase the risk of diagnostic pitfalls and misclassification (10).

A prior benign skin lesion may offer an additional diagnostic clue, as malignant transformation has been reported (11, 12). In the present case, the occurrence of PCAC in the same region as a previously excised syringoma raises the question of whether the carcinoma may have arisen from the earlier lesion. However, considering the distinct histogenetic origins of eccrine and apocrine glands, the development of apocrine carcinoma from a benign eccrine tumor is unlikely and may suggest that mixed apocrine differentiation was unrecognized at that time.

Furthermore, distinguishing PCAC from breast cancer - whether occult metastasis or arising from accessory mammary tissue - requires both clinical evaluation and comprehensive imaging. Accessory breast tissue can be found along the embryonic milk line, which extends bilaterally from the axilla to the groin. Cancers arising in these areas may therefore be misattributed to breast origin based on location alone, which is particularly relevant considering the axilla is the most frequent site of primary apocrine apocrine carcinoma (1). Primary internal adenocarcinomas that have metastasized to the skin typically indicate advanced disease and poor prognosis, whereas PCAC usually follows a more indolent course. Prognosis is chiefly influenced by the presence of lymph node metastases and the extent of cellular anaplasia, with the absence of nodal involvement conferring a significant survival benefit (1).

The rarity of the disease has prevented the establishment of standardized treatment protocols. Wide local excision is generally considered the treatment of choice. Although regional lymph node involvement is frequently observed, there is no consensus on the role of (radical) lymphadenectomy in reducing the risk of disease recurrence (1, 3, 13). Adjuvant radiotherapy may offer benefit in moderate to poorly differentiated lesions with more advanced locoregional involvement (1, 12, 14). Data regarding systemic therapy in disseminated disease is limited, with some studies demonstrating potential benefit from chemotherapy or endocrine treatments, including anti-androgen therapy (15–18).

A lack of distinctive clinical features, slow progression, and histological ambiguity may result in a substantial delay before appropriate therapy is initiated (3). This case underscores the importance of maintaining a broad differential diagnosis when evaluating tumors with non-specific or overlapping clinico-pathological features. Clinicians, particularly senologists, should consider the possibility of PCAC when assessing a suspected cutaneous manifestation of triple-negative breast carcinoma. Recognizing this distinction is crucial to avoid misdiagnosis, which could lead to unnecessary surgery or inappropriate systemic therapy. Accurate identification ensures timely, appropriate treatment and ultimately improves patient outcomes.