Maturing papillomatous nevoid melanoma in the scalp mimicking recurrent melanocytic nevus: A case report of previously undescribed subtype of nevoid melanoma.

Nevoid melanoma is a subtype of melanoma that histologically resembles a melanocytic nevus. Two subtypes have been proposed for nevoid melanoma, namely papillomatous and maturing. Here, we report the case of a 67-year-old woman who developed two nevoid melanomas on her scalp with composite histological features of papillomatous and maturing subtypes after electrocautery of a nearby solitary scalp papule. The histology of both lesions was very similar, papillary in shape, and both comprised two melanocyte populations, including large atypical melanocytes and small non-atypical melanocytes. Whole-exome sequencing was performed in one of the two lesions, which revealed a high mutation burden (17 mutations/megabase) with co-deletion of CDKN2A. Additional immunohistochemistry revealed that the large and small melanocytes in both lesions were completely negative for p16 and MTAP. A final diagnosis of nevoid melanoma was made. To our knowledge, this is the first report of a nevoid melanoma with both features of papillomatous and maturing subtypes. Pathologists should be aware of this subtype of melanoma to avoid misdiagnosis as a mitotically active melanocytic nevus. In this case, immunohistochemistry for p16 and MTAP, in addition to molecular analysis, helped in the final diagnosis.

"Puffy shirt appearance": Cell crowding at low magnification may represent nevoid melanoma.

BACKGROUND: Melanoma, particularly nevoid melanoma, can masquerade as benign. Helpful differentiating features include nuclear pleomorphism, atypia, prominent nucleoli, absent maturation, and increased mitotic figures. These can be subtle and easily missed unless carefully sought. Thus, the "puffy shirt appearance" concept was born from a Seinfeld episode in which the namesake character unintentionally agreed to wear a pirate-like puffy shirt. Consequently, he found himself out of place, sporting an outfit with "too much shirt in too little space". Similarly, at low-power, nevoid melanoma appears to have "too many cells in too little space". This is more pronounced and easier to appreciate when there is an associated nevus, where crowded, subtly malignant melanocytes stand out from the evenly distributed, more spaced out benign melanocytes. METHODS: Twelve practicing dermatopathologists familiar with the puffy shirt concept in the context of melanoma were surveyed. RESULTS: Hundred percent of participants found it most helpful as a triaging tool, prompting additional work up including higher magnification evaluation, additional levels, consultation, and/or immunohistochemistry. CONCLUSIONS: The crowded cells in the "puffy shirt appearance" catch the eye and should provoke a more thorough inspection of the lesion. This sign is not pathognomonic for melanoma, but prompts more careful evaluation and helps prevent misdiagnosis.

Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma.

BACKGROUND: Nevoid melanomas include melanomas with a low power silhouette similar to melanocytic nevi. However, at higher power magnification, nevoid melanoma may have severe nuclear atypia and dermal mitoses. METHODS: We performed a clinical, pathological and molecular study on a series of 58 examples of nevoid melanoma, excluding cases with spitzoid morphology. RESULTS: We identified distinct morphologic patterns: 'classic' nevoid melanoma, superficial spreading melanomas with nevoid invasive melanoma, lentigo maligna with nevoid invasive melanoma and deep penetrating nevus-like nevoid melanoma. Fluorescence in situ hybridization (FISH) was positive in 74% of cases. Copy number gains in 8q24 were common in amelanotic nevoid melanoma. The median follow-up was 28 months (range 140). At last follow-up, 37 patients had no evidence of disease, 3 were alive with metastases and 6 died from metastatic melanoma. Of these six patients who died, four had a sentinel lymph node biopsy (SLNB) performed, which was negative in all four. CONCLUSIONS: We describe distinct clues to the diagnosis of nevoid melanoma including occult intraepidermal atypia, and expansile nesting resulting in asymmetric silhouette or dermal papillae expansion. We also describe that nevoid melanoma have infrequent SLNB involvement in aggressive cases, and have frequent 8q24 gains rather than 9p21 deletions. Our results suggest that nevoid melanoma are distinct from spitzoid melanomas and should be distinguished.

Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature.

Indeterminate melanocytic proliferations of the conjunctiva have both benign and malignant features that previously made these lesions nearly impossible to categorize in existing classification schemes. With the evolution of immunohistochemistry and molecular genetics, however, subclassifications have emerged that allow for a more tailored diagnosis and management. These conjunctival melanocytic proliferations include deep penetrating nevus, granular cell nevus, and nevoid melanoma. There remains a small subset of conjunctival melanocytic proliferations that defy precise characterization as nevi, primary acquired melanosis, or melanomas despite currently available ancillary diagnostic modalities and remain indeterminate. We highlight these unusual types of nevi and melanomas, with an update on their morphologic, immunohistochemical, and molecular genetic characteristics.

Computer-Aided Assessment of Melanocytic Lesions by Means of a Mitosis Algorithm.

An increasing number of pathology laboratories are now fully digitised, using whole slide imaging (WSI) for routine diagnostics. WSI paves the road to use artificial intelligence (AI) that will play an increasing role in computer-aided diagnosis (CAD). In melanocytic skin lesions, the presence of a dermal mitosis may be an important clue for an intermediate or a malignant lesion and may indicate worse prognosis. In this study a mitosis algorithm primarily developed for breast carcinoma is applied to melanocytic skin lesions. This study aimed to assess whether the algorithm could be used in diagnosing melanocytic lesions, and to study the added value in diagnosing melanocytic lesions in a practical setting. WSI's of a set of hematoxylin and eosin (H&E) stained slides of 99 melanocytic lesions (35 nevi, 4 intermediate melanocytic lesions, and 60 malignant melanomas, including 10 nevoid melanomas), for which a consensus diagnosis was reached by three academic pathologists, were subjected to a mitosis algorithm based on AI. Two academic and six general pathologists specialized in dermatopathology examined the WSI cases two times, first without mitosis annotations and after a washout period of at least 2 months with mitosis annotations based on the algorithm. The algorithm indicated true mitosis in lesional cells, i.e., melanocytes, and non-lesional cells, i.e., mainly keratinocytes and inflammatory cells. A high number of false positive mitosis was indicated as well, comprising melanin pigment, sebaceous glands nuclei, and spindle cell nuclei such as stromal cells and neuroid differentiated melanocytes. All but one pathologist reported more often a dermal mitosis with the mitosis algorithm, which on a regular basis, was incorrectly attributed to mitoses from mainly inflammatory cells. The overall concordance of the pathologists with the consensus diagnosis for all cases excluding nevoid melanoma (n = 89) appeared to be comparable with and without the use of AI (89% vs. 90%). However, the concordance increased by using AI in nevoid melanoma cases (n = 10) (75% vs. 68%). This study showed that in general cases, pathologists perform similarly with the aid of a mitosis algorithm developed primarily for breast cancer. In nevoid melanoma cases, pathologists perform better with the algorithm. From this study, it can be learned that pathologists need to be aware of potential pitfalls using CAD on H&E slides, e.g., misinterpreting dermal mitoses in non-melanotic cells.

Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report.

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.

Nevoid iris melanoma, case report. / Melanoma nevoide de iris, a propósito de un caso.

CASE REPORT: The case is presented of a patient with diagnosis of iris nevus in the left eye in youth with a poor follow-up, who referred a decreased visual acuity in that eye. A hyphaema and a 3×4×3mm nodule with irregular pigmentation was observed. Excision of the tumour and histological analysis confirmed the suspicion of iris melanoma in stage Ia. DISCUSSION: Despite the low grade malignancy of iris melanoma and the low frequency of transformation of iris nevus into melanoma, a follow-up is required for its early diagnosis and treatment.

Clinical and histopathological analysis of three cases of nevoid melanoma / 中华皮肤科杂志

Objective:To investigate clinical and histopathological characteristics of nevoid melanoma.Methods:A retrospective analysis was carried out on clinical and histopathological data collected from 3 patients with nevoid melanoma diagnosed in Department of Dermatology, Xijing Hospital from 2000 to 2020.Results:Among the 3 patients with nevoid melanoma, 2 were females and 1 was male. Skin lesions initially manifested as black macules and papules. After surgical resection, 2 patients developed new nodular lesions or recurrent skin lesions which enlarged into plaques. Histopathological examination showed proliferation of epithelioid melanocytes in the epidermis and dermis, with cytological atypia and some deeply stained nuclei. Immunohistochemical study revealed positive staining for Melan-A and S100 in tumor cells in the skin lesions, diffusely positive staining for HMB45 in dermal tumor cells, locally negative staining for HMB45 in the deep dermis, increased Ki67 proliferation index, and active expression of cyclin D1.Conclusion:Nevoid melanoma is easy to be misdiagnosed as pigmented nevi or seborrheic keratosis; when recurrence or metastasis occurs in patients with histologically diagnosed pigmented nevi, attention should be paid to the possibility of nevoid melanoma.

Nodal Melanoma Metastasis under Infliximab Therapy in a Patient with Nevoid Melanoma First Misdiagnosed as Benign Nevus: A Potentially Dangerous Diagnostic Pitfall in the Era of Biologic Therapies.

We report the case of a 53-year-old Caucasian woman who developed nodal melanoma metastasis under infliximab therapy 2 years after the removal of a nevoid melanoma, which was initially misdiagnosed as a benign compound nevus. This case illustrates the potential link between tumor necrosis factor (TNF)-α inhibition and the reactivation of latent melanoma. Furthermore, this case highlights the need for a complete skin examination before using anti-TNF-α therapy to rule out atypical malignant lesions or melanomas that can easily be missed because of presentations such as nevoid melanoma.

Nevoid Melanoma.

This article discusses the key features of nevoid melanoma. Gross features, microscopic features, immunohistochemistry, differential diagnosis, diagnosis, prognosis, and treatment are also discussed.