Malignant Hidroacanthoma Simplex: A Case Report Open Access

Malignant hidroacanthoma simplex (MHS), a rare malignant neoplasm originating from eccrine duct epithelium, poses significant diagnostic and management challenges due to its clinical mimicry of benign lesions and limited reported cases. Since its first description in 1963 [1], fewer than 40 cases have been reported in the English literature as of December 2024, based on a systematic search of PubMed, Web of Science, and Embase using the keywords “Malignant hidroacanthoma simplex” AND (“case report” OR “rare disease”). This extreme rarity highlights critical gaps in understanding its natural history, particularly the timeline and triggers of malignant transformation from its precursor, hidroacanthoma simplex. To our knowledge, the estimated 20-year latency period between patient-reported lesion emergence and histopathologically confirmed malignancy ranks among the longest documented intervals in dermatological oncology, though the absence of longitudinal clinical records necessitates cautious interpretation.

What distinguishes this case is its illumination of two underrecognized clinical phenomena: the role of chronic mechanical trauma in accelerating tumor progression and the long-term outcomes of local excision in noninvasive disease. The patient’s history of decades-long lesion persistence, followed by rapid enlargement after repeated trauma (e.g., self-induced injury and scratching), suggests a potential link between mechanical stress and malignant transformation, a hypothesis rarely explored in existing literature. Furthermore, the successful management with wide local excision and 15-month recurrence-free follow-up provides robust evidence supporting surgical resection as an effective strategy for non-dermal invasive MHS, a subset of the disease with unclear prognostic implications.

Clinically, this case addresses a key unmet need in dermatology: the early identification of indolent cutaneous masses in elderly patients that may harbor occult malignancy. By documenting the longest reported interval between lesion onset and malignant conversion, it underscores the importance of long-term surveillance for seemingly stable skin lesions, especially those subjected to chronic irritation. Additionally, the pathological finding of tumor cells confined to the epidermis without dermal invasion challenges current classifications of epidermotropic carcinomas, prompting reevaluation of how we differentiate in situ versus invasive variants of eccrine-derived neoplasms. These insights not only expand our understanding of MHS pathogenesis but also offer practical guidance for clinicians managing similar lesions, emphasizing the value of histopathological confirmation and personalized follow-up protocols to optimize outcomes in this rare disease.

A 64-year-old woman reported a slowly enlarging right lumbar mass with a 20-year history, and the 20-year duration was estimated from patient history without prior medical documentation. Over the past 5 years, the lesion had grown more rapidly. Physical examination identified a solitary, irregularly bordered, reddish-brown plaque (3.5 cm × 4.0 cm, Fig. 1) with a crusted surface. No regional lymphadenopathy was detected. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546700).

Histopathological examination revealed hyperkeratosis, acanthosis, and focal parakeratosis. The stratum spinosum exhibited marked hypertrophy, with nests of tumor cells infiltrating the epidermis. These cells displayed rectangular or oval morphology, pale eosinophilic cytoplasm, nuclear vacuolization, inconspicuous nucleoli, and occasional atypical mitoses. Tumor cells were confined to the epidermis without dermal invasion (Fig. 2a, HE, ×100, Fig. 2b, HE, ×400).

The surgical approach consisted of wide local excision with 1-cm clinical margins, consistent with current recommendations for adnexal carcinomas with Breslow thickness <2 mm [2]. Postoperative histopathology confirmed complete tumor removal. Preoperative CT and ultrasonography revealed no evidence of locoregional lymph node metastasis; therefore, wide local excision of the lesion was performed without regional lymph node dissection. Postoperatively, the patient underwent scheduled clinical follow-up comprising physical examinations every 3 months, with focused assessment of the surgical scar and regional lymph nodes; ultrasonographic surveillance of the tumor bed and draining lymph node basins at 6 and 12 months. At the 15-month follow-up interval, imaging studies demonstrated no residual tumor or lymph node involvement. The patient remained disease-free with satisfactory postoperative recovery and no signs of recurrence.

MHS lesions predominantly involve the lower extremities (over 50%), though they may also occur on the scalp, face, and ears (<20%), upper limbs (11%), or trunk and abdomen (9%) [3]. Due to its nonspecific clinical presentation – manifesting as verrucous red/brown plaques, polypoid growths, or long-standing ulcerative lesions – and its rarity, MHS is frequently misdiagnosed as seborrheic keratosis, basal cell carcinoma, or Bowen’s disease. Primary tumors typically average 2.4 cm in size [3]; in this case, the tumor reached 4 cm in diameter due to prolonged disease progression, and the retrospective estimation of disease duration based on patient recall introduces potential recall bias. While the 20-year interval is remarkable, prospective documentation of similar cases with serial imaging would strengthen chronological accuracy. MHS primarily affects elderly individuals aged 60–80 years [4]. The interval from disease onset to definitive treatment varies widely, as early lesions are often asymptomatic and overlooked until ulceration develops.

MHS may arise de novo or result from malignant transformation of hidroacanthoma simplex [4], characterized by sudden tumor enlargement, tenderness, ulceration, and possible malodor. Based on the clinical course and presentation, this case likely represents malignant transformation of preexisting hidroacanthoma simplex. Notably, the patient inadvertently damaged the protruding portion of the lesion and reported persistent pruritus with repeated scratching, obscuring its original features and complicating diagnostic evaluation.

Histopathologically, MHS is characterized by atypical tumor cells predominantly confined to the epidermis without breaching the basement membrane, also termed intraepidermal eccrine porocarcinoma in situ [5]. Given its close association with hidroacanthoma simplex, MHS may exhibit overlapping histological features, including uniformly small, rectangular, or oval tumor cells with well-defined borders, pale eosinophilic cytoplasm, vacuolated nuclei, and inconspicuous nucleoli [6, 7]. Distinguishing MHS from seborrheic keratosis is critical due to their frequent clinical and dermoscopic similarities, which may lead to misdiagnosis and delayed treatment if not adequately evaluated histologically. The latter typically demonstrates hyperkeratosis, mixed basaloid and squamoid proliferation, and horn cysts, while lacking hallmark features of hidroacanthoma simplex, such as eccrine ductal differentiation and intracytoplasmic lumina [8]. Histopathological and immunohistochemical analyses remain the diagnostic gold standard for this entity. While these conventional methods provide essential morphological characterization, emerging molecular insights are refining our understanding of disease pathogenesis. Notably, advances in molecular diagnostics have revealed that YAP1-MAML2 fusion represents the most prevalent genetic alteration in both MHS and porocarcinoma, offering critical clues to their shared oncogenic mechanisms [9].

Suzaki et al. [10] described dermoscopic features of MHS: hidroacanthoma simplex is present as white globular structures on a light-brown background, whereas MHS exhibits an irregular white globular network alongside prominent polymorphous vascular patterns, including dotted, linear-irregular, glomerular, and hairpin vessels. The lack of preoperative dermoscopic documentation in the current study limited precise delineation of early morphological alterations linked to malignant transformation. Future investigations incorporating serial dermoscopic imaging may improve the identification of high-risk features at earlier stages.

MHS exhibits metastatic potential and a propensity for local recurrence. In early disease progression, lymphovascular invasion in the skin and a tendency for cutaneous metastasis may occur [10]. The metastatic rate to regional lymph nodes and adjacent skin is approximately 20%, and the prognosis becomes significantly poorer once metastasis develops [10]. Primary lesions can be managed with local surgical excision, while metastatic disease requires systemic chemotherapy [11].

In summary, MHS is a rare malignancy with nonspecific clinical features. Clinicians should prioritize early surgical excision for suspected cases to facilitate histopathological confirmation. Postoperative management must emphasize rigorous follow-up, including comprehensive lymph node evaluation, to monitor for potential metastatic spread. Given the tumor’s propensity for lymph node metastasis, vigilance remains paramount in optimizing patient outcomes.

This study protocol was reviewed, and ethical approval was given by the Clinical Research Ethics Review Committee, Affiliated Hospital of Hebei University Number (HBDYFSYY-2023-211). Written informed consent was obtained from the patient 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 supported by Project of Baoding Science and Technology Bureau (Number: 2241ZF311) and Foundation Project of the Affiliated Hospital of Hebei University (Number: 2022QB29).

Meng Zhang and Xiangxiang Ren identified the patient’s case as a potential candidate for a case report; collected all relevant clinical data including patient history, physical examination findings, and treatment course; drafted the initial manuscript; and incorporated revisions based on feedback from coauthors. Fan Yang performed essential diagnostic evaluations to characterize the underlying pathology that included histological examination of the skin biopsy to assess tissue morphology and immunophenotyping studies to identify the type and activation state of infiltrating lymphocytes. Tianhao Xie and Lingyun Liu supervised the management of the patient throughout the course of their care; provided mentorship and guidance to the first author during case identification, data collection, and manuscript writing; reviewed and critically revised all drafts of the manuscript, ensuring scientific accuracy and clarity; and provided final approval for submission of the manuscript.

The data that support the findings of this study are not publicly available due to their containing sensitive patient health information that could compromise participant privacy, but are available from the corresponding author Xiangxiang Ren upon reasonable request.