Malignant Hidradenoma of the Scalp: A Rare Case with Diagnostic Challenges and Immunohistochemical Insights Open Access

Hidradenocarcinomas are infrequent malignant tumors arising from the intradermal duct of eccrine sweat glands [1]. In most cases, they present as asymptomatic cutaneous lesions with no specific distinguishable features or have nonspecific clinical presentation with indistinct pathological features [2, 3]. It accounts for approximately 6% of malignant eccrine tumor and less than 0.001% of all tumors [4]. Determination of its incidence and precise number of cases reported is difficult due to the various synonyms including malignant acrospiroma, clear-cell hidradenocarcinoma, malignant clear-cell hidradenoma, solid-cystic adenocarcinoma, nodular hidradenocarcinoma, malignant clear-cell myoepithelioma, and clear-cell eccrine carcinoma [1‒6]. It can arise conventionally de novo and rarely from a pre-existing hidradenoma [7, 8]. The most common site is the face or extremities, but cases have also been reported at other sites like the abdomen, trunk, groin, and rarely on the scalp, elbow, and digits [9]. The most common age-group of presentation is fifth to the seventh decade of life with the mean age of onset being 50 years. Though reported to be more common in females [4], there does not seem to be an obvious gender predominance [2]. The tumor has the potential for recurrence, metastasis, and often results in death.

A 57-year-old man presented with a painless swelling over the scalp since 2½ years. It was insidious in onset, initially small with a gradual increase in the size over a period of 1½ years, and has been stable in the last 1 year (shown in Fig. 1). There is history of multiple traumas to the swelling while combing his hair following which it was associated with serous discharge over a period of last 2 months. On local examination, a swelling measuring 4 × 5 cm was seen over the left temporo-parietal region, 3 cm above the ear lobe, spherical in shape, pedunculated with sero-sanguinous discharge, and firm in consistency. Ultrasonological studies showed a heteroechoic well-defined soft tissue lesion in the left parietal aspect, superficial to the aponeurosis of the scalp with no frank evidence of intracranial extension. Doppler studies showed increased vascularity in the lesion. Clinically, the patient was suspected to have an infected sebaceous cyst. A wide excision of the lesion was done under local anesthesia. Postoperative period was uneventful and the patient was clinically stable and asymptomatic.

On macroscopic examination, a nodular lesion was noted on skin measuring 4 × 5 cm. Outer surface of the globular mass shows sinus opening on the skin surface. On cut surface, lobules of gray white solid areas are seen (shown in Fig. 2).

Histopathological examination showed skin with a deep dermal tumor composed of nodules and islands of polygonal cells with moderate eosinophilic to clear cytoplasm, squamoid cells, all with vesicular focally pleomorphic nuclei, atypical, and with increased mitotic activity of 6/10 HPF. Focal acinar and ductular pattern with columnar cell lining was seen. Bizarre cells were also noted (shown in Figs. 3-6). Focal cystic change, traversing trabecular hyaline bands, and sparse chronic inflammation were present. There was invasion of stroma. No necrosis was noted. Based on microscopy, a diagnosis of atypical hidradenoma/malignant hidradenoma was given. Immunohistochemical study performed showed 22% expression of Ki-67 and 14% expression of p53, thus confirming the diagnosis of malignant hidradenoma (shown in Figs. 7, 8). No evidence of lymph node metastases or distant metastases was found. Surgical margins were clear. The patient was followed up for 5 years and did not show any signs of recurrence or metastasis.

Hidradenocarcinomas, though extremely rare, represent a highly aggressive form of cutaneous adnexal tumors originating from eccrine sweat glands [3]. Histologically, sweat glands are classified into two major types: eccrine and apocrine. Eccrine glands are distributed widely across the body, with the highest concentrations found in the palms, soles, and axillae, while apocrine glands are more localized to the axillae, perineum, and breast. Despite the relatively rare occurrence of primary eccrine carcinomas accounting to less than 0.01% of all skin cancers, hidradenocarcinomas – subtypes of adenocarcinomas arising from these glands – are particularly aggressive and often present significant diagnostic and clinical challenges [4, 9]. Ultrastructural and enzyme histochemical studies have shown that it appears to represent a transitional tumor, sharing features of eccrine poroma and eccrine spiradenoma [8].

These tumors are often initially identified as benign solitary lesions, ranging in size from 1 to 5 cm, with a slow and circumscribed expansion [3]. However, their malignant potential becomes evident upon recurrence as the tumor demonstrates more rapid growth, deeper tissue invasion, and metastatic spread, typically via hematogenous routes [5]. As these lesions progress, patients may experience symptoms related to the involvement of distant organs [3]. This underscores the importance of early detection and intervention to prevent the high morbidity associated with advanced disease stages.

Microscopically, hidradenocarcinomas exhibit distinctive features such as intradermal epithelial lobules with cystic spaces and faintly eosinophilic material. These lobules are lined by cuboidal or columnar cells and are often surrounded by glycogen-rich clear cells, which can be identified using PAS staining [8]. The presence of both solid tumor components and clear cells in various stages of differentiation is a hallmark of hidradenocarcinomas, and the cellular architecture can include occasional spindle cells and squamous differentiation [6, 8]. The histological complexity often presents challenges in differentiating benign from malignant hidradenocarcinomas as some tumors may lack the classic features of malignancy, such as circumscription, deep extension, or vascular invasion.

The differentiation between benign and malignant hidradenomas relies on several key histological criteria. Malignant tumors typically exhibit an infiltrative growth pattern, nuclear pleomorphism, necrosis, perineural invasion, and increased mitotic activity. However, some tumors – termed “atypical hidradenomas” – may present with focal atypical features, such as nuclear pleomorphism or mitotic activity but without evidence of full malignancy [9]. Atypical hidradenomas have a more indolent clinical course, with recurrence being possible but metastasis being exceedingly rare [9]. Immunohistochemical markers such as Ki-67, PHH3, and mitotic count can aid in distinguishing between these atypical tumors and fully malignant cases, with elevated mitotic rate ≥4 mitoses per 10 HPFs, Ki-67 >11%, and/or PHH3 >0.7% expression correlating with malignant behavior [6, 7]. Our case showed a high mitotic count with an elevated Ki67 percentage, favoring malignancy.

Clinically, hidradenocarcinomas can be mistaken for a wide variety of benign and malignant lesions. These include benign cystic lesions such as infundibular or pilar cysts, as well as cutaneous tuberculosis and dermatofibrosarcoma protuberans. Malignant lesions like basal cell carcinoma, squamous cell carcinoma, and malignant melanoma can also be considered in differential diagnosis [4]. Histopathologic evaluations, including PAS staining and immunohistochemical markers like cytokeratin, EMA, and CEA, can help confirm the eccrine origin of hidradenocarcinomas. Moreover, the expression of androgen receptors, estrogen receptors, progesterone receptors, EGFR, and HER-2 in some cases adds to the complexity of their differentiation from other malignancies, including primary carcinomas of the breast, salivary glands, and lungs, as well as metastatic clear cell carcinomas from the thyroid or renal cell carcinomas [4]. Distinguishing hidradenocarcinomas from these lesions using clinico-radiological and immunohistochemical correlation is crucial for guiding appropriate treatment decisions.

The primary treatment modality for hidradenocarcinomas remains wide local excision, with or without regional lymph node dissection, depending on the extent of the disease. Adequate surgical margins – preferably at least 3 cm – are essential to ensure complete tumor resection and reduce the risk of local recurrence. In cases where this is not possible, thorough histological assessment of lateral margins is critical [4]. While chemotherapy and radiotherapy may be considered in certain cases, there is limited evidence supporting their efficacy in treating hidradenocarcinomas. Unfortunately, the prognosis for patients with advanced diseases, particularly those with systemic metastasis, remains poor [1].

Our report is based on a single case, which limits the ability to generalize findings and draw broader conclusions about the disease. Furthermore, the lack of molecular profiling and limited immunohistochemical testing, due to financial constraints, restricts a deeper understanding of the tumor’s genetic characteristics and potential targeted therapies.

In conclusion, hidradenocarcinomas are rare but highly aggressive tumors that present significant diagnostic and therapeutic challenges. Early diagnosis, careful histopathological examination, and wide surgical excision are essential for improving patient outcomes and minimizing the risk of metastasis. Ongoing research into molecular profiling and targeted therapies may provide new opportunities for treatment in the future, potentially improving the prognosis for individuals affected by this rare malignancy. This case report adheres to the guidelines outlined in the CARE (Case Report) Checklist, which is available as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545383).

This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines. Written informed consent was obtained from the participant to participate in the study. Written informed consent was obtained from participants for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Design of the work, the acquisition, analysis, or interpretation of data for the work, and drafting the work or reviewing it critically for important intellectual content: Dr. Anuradha Calicut Kini Rao and Dr. Rakshatha Nayak. Final approval of the version to be published: Dr. P.S.M. Ameer Ali, Dr. Shikha Jayasheelan, and Dr. Kudurugundi Basavaraju Vatsala. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: Dr. Anuradha Calicut Kini Rao, Dr. Rakshatha Nayak, Dr. P.S.M. Ameer Ali, Dr. Shikha Jayasheelan, and Dr. Kudurugundi Basavaraju Vatsala.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed at the corresponding author.