The Dermatopathological Diagnosis of Malignant Hidradenoma (Clear Cell Hidradenocarcinoma) and Wide Surgical Excision With Pathological Margin Control: A Systematic Review of Randomized Controlled Trials and Primary Studies

Introduction: Hidradenocarcinoma (HAC), the malignant counterpart of nodular (clear cell) hidradenoma, is a rare cutaneous adnexal carcinoma with eccrine/apocrine ductal differentiation. Its dermatopathological separation from benign and atypical hidradenoma is notoriously difficult, and the optimal surgical strategy, wide local excision (WLE) versus excision with complete pathological margin control such as Mohs micrographic surgery (MMS), remains undefined. Historical case-report literature portrays HAC as highly aggressive, whereas population-based registries suggest a favourable prognosis. We aimed to synthesise contemporary primary evidence on the dermatopathological diagnosis of HAC and on oncological outcomes after margin-controlled surgical excision. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Literature published from January 2011 to November 2026 was searched in PubMed, Europe PMC, Google Scholar, Semantic Scholar and ClinicalTrials.gov, with supplementary citation chasing. Randomised controlled trials (RCTs), comparative studies, cohorts and case series (≥3 patients) were eligible; case reports were excluded, and systematic or narrative reviews were reserved for the Discussion. Risk of bias was assessed with the Joanna Briggs Institute (JBI) checklist for case series and an adapted Newcastle–Ottawa Scale (NOS) for registry cohorts. Proportions were pooled using the Freeman–Tukey double-arcsine transformation with DerSimonian–Laird random-effects models; Hartung–Knapp–Sidik–Jonkman (HKSJ) intervals and 95% prediction intervals were computed when ≥3 studies were available. Overlapping registry populations were never pooled together. Certainty of evidence was graded with GRADE. Results: Of 668 unique records screened, 14 primary studies met the eligibility criteria: 10 HAC cohorts or series (≈1,286 non-overlapping patients; four population-based registry cohorts, six institutional or molecular series) and four molecular series of benign hidradenoma used as diagnostic comparators. No RCT was identified. The pooled proportion of men was 55.1% (95% CI 51.5–58.8; I² = 19%) and 43.6% of tumours arose in the head and neck. Primary-site surgery was performed in 90.1% (88.2–91.9), radiotherapy in 12.5% (5.5–21.9; I² = 95%) and chemotherapy in 1.7% (1.0–2.5). Crude disease-specific mortality was 1.9% (0.6–3.7; I² = 0%), and the pooled 10-year disease-specific survival was 91.1% (89.1–92.7). Five-year survival fell from 91.1% in stage I to 53.3% in stage III, and from 95.8% in node-negative to 53.6% in node-positive disease. Regional nodal positivity among pathologically staged patients was 31.9% (0.5–76.4). After MMS or complete re-excision with histologically clear margins, pooled local recurrence was 0.0% (0.0–5.8; 3 series, 32 patients). Recurrence or metastasis occurred in 7.0% (0.0–23.9) of low-grade versus 100% of high-grade HAC (test for subgroup difference p < 0.001; odds ratio 169, 95% CI 2.9–9,876). MAML2 rearrangement was present in 66.6% (49.3–82.0) of benign hidradenomas and 75.0% of HAC (p for difference = 0.63), indicating a lineage rather than a malignancy marker. Certainty of evidence ranged from low to very low. Discussion: Contemporary data refute the historical view of uniformly lethal behaviour: HAC is predominantly a low-grade, surgically curable carcinoma whose lethality is concentrated in high-grade, node-positive and advanced-stage disease. Histological grade, determined by an asymmetric infiltrative base, perineural invasion, necrosis, pleomorphism and proliferative activity, is the dominant prognostic determinant, whereas MAML2 status supports hidradenoma-lineage origin but does not discriminate malignancy. Complete histological margin control was associated with negligible local recurrence, but comparative evidence between MMS and WLE is lacking. Conclusion: Diagnosis of HAC should rest on adequate sampling of the tumour base with explicit grading. Definitive treatment should achieve complete pathological margin control, through MMS or peripheral and deep en face margin assessment where feasible, or WLE with complete histological margin evaluation, with nodal staging reserved for high-grade or advanced tumours. Prospective multicentre registries with standardised grading and margin reporting are required.