A 70-year-old woman with no significant past medical history was evaluated in the dermatology clinic for a chronic abdominal cutaneous lesion of more than 10 years' duration, characterized by slow and progressive growth. Over the preceding months, the central portion of the lesion had become elevated and demonstrated an increased propensity for spontaneous bleeding. On physical examination, a large, pigmented plaque measuring 18 × 12 cm was observed on the right abdominal flank (Figure 1). The lesion displayed sharply demarcated borders, heterogeneous brown pigmentation, and a rough, keratotic surface. At its centre, a pinkish, friable tumoral component was noted, with marked susceptibility to bleeding upon minimal manipulation. The lesion was surgically excised, and histopathological and immunohistochemical analyses were subsequently undertaken. (Figure 2). Invasive squamous cell carcinoma (SCC) arising within a giant melanoacanthoma. Histopathological examination of the peripheral portion of the lesion revealed an intraepidermal proliferation of keratinocytes and melanocytes, associated with marked acanthosis and multiple horn pseudocysts (Figure 2d,e). Scattered melanophage histiocytes were identified within the dermis. Immunohistochemical staining for Melan-A and HMB-45 highlighted melanocytes with prominent dendritic morphology. In contrast, the central tumour-forming area demonstrated an atypical neoplastic proliferation of moderately differentiated keratinocytes exhibiting an invasive growth pattern. The neoplastic cells showed enlarged nuclei, atypical mitotic figures, and focal keratinization (Figure 2). Ki-67 expression was markedly increased in this central component compared with the peripheral areas (Figure 3). Both the peripheral and central components of the lesion were positive for p40 and negative for PRAME. Melan-A and HMB-45 immunostaining were negative in the central (tumoral) area. p53 expression was negative in both the tumour and peripheral regions, whereas p16 immunoreactivity was observed in the SCC component. Immunohistochemical staining for HPV (K1H8) was positive in focal cytoplasmic areas of the SCC, and combined Ki-67 and p16 staining demonstrated positivity in a subset of neoplastic cells (Figure 3). Melanoacanthoma is generally considered a rare, intensely pigmented variant of seborrheic keratosis (SK), histopathologically characterized by a proliferation of basaloid and spinous keratinocytes interspersed with numerous dendritic melanocytes 1. First described in the 1960s, it typically presents as a solitary, slowly growing cutaneous lesion arising on the head, neck, or trunk of older individuals, and it may clinically resemble SK, pigmented Bowen disease, or melanoma. Lesions may reach diameters of 3 cm or more, and giant forms exceeding 15 cm have been reported 2, 3. Histopathologically, basaloid cells typically form nests or islands, whereas spinous keratinocytes are arranged in discrete foci with central keratinization, resulting in horn pearl (endokeratinization) formation. Dendritic melanocytes are numerous, contain mature melanosomes, and exhibit intense pigmentation, while adjacent keratinocytes show only minimal melanin deposition. In addition, melanin-laden macrophages are frequently identified within the superficial dermis 2. Although SK and its variants are considered benign intraepidermal neoplasms, malignant transformation—most commonly to SCC—has been repeatedly documented, albeit rarely 4-7. Most documented cases are reported as isolated cases or small case series, often with limited histopathological or immunohistochemical data. In the largest series published to date, Goto and colleagues described 11 cases of SCC arising within SK, four of which were invasive 8. In three of these four cases (75%), loss of p16 immunoexpression was observed. The authors suggest that malignant transformation may be driven by mutations in TP53 and PTEN, with tumour invasion associated with inactivating mutations in CDKN2A. In contrast, in the majority (86%) of SCC in situ arising within SK, p16 immunostaining was positive, raising the possibility of an association with human papillomavirus (HPV) infection. Thus, in situ or invasive SCC can arise within SK, particularly in large, long-standing lesions in elderly patients, and may present with clinical features such as rapid growth, nodularity, ulceration, or spontaneous bleeding 8. Importantly, the malignant component in these cases often shows basaloid or squamoid cytology, bowenoid or pagetoid intraepidermal spread, and in invasive cases, a clear infiltrative pattern with increased mitotic activity and nuclear atypia. In the present case, the central portion of the lesion harboured a moderately differentiated invasive SCC arising within a long-standing, large, densely pigmented keratotic lesion exhibiting histopathological features consistent with melanoacanthoma. Careful histopathological examination demonstrated a well-defined transition from the benign peripheral component to an atypical keratinocytic proliferation in the central region, characterized by enlarged nuclei, atypical mitotic figures, and focal keratinization. The immunohistochemical profile further supported malignant transformation, revealing a markedly increased Ki-67 proliferative index, loss of HMB-45 and Melan-A expression, and strong p40 positivity within the carcinoma component. Additionally, the absence of p53 expression in both the benign and malignant components, together with strong p16 positivity in the SCC, raises the possibility of HPV involvement in tumour pathogenesis 9. Immunohistochemical staining for HPV (clone K1H8) demonstrated focal cytoplasmic positivity in isolated neoplastic cells within the SCC. The prevalence, risk factors, and pathophysiological mechanisms underlying the development of SCC arising in SK remain largely unknown, and further studies are required to better elucidate this entity. Careful clinicopathological correlation, comprehensive assessment of long-standing pigmented lesions that undergo recent morphological changes, and adequately extensive tissue sampling are essential to ensure accurate diagnosis and appropriate management 10. Ángel Fernández-Camporro: data curation, writing, original draft preparation. Julián José Ahijado-González: conceptualization, methodology. Eva Miranda-Martínez: supervision. The authors received no specific funding for this work. All patients in this manuscript have given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Camporro et al. (Mon,) studied this question.