Comparative Study

Authors: Cecilia Lezcano, Achim A Jungbluth, Kishwer S Nehal...

PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen that was isolated by autologous T cells in a melanoma patient. While frequent PRAME mRNA expression is well documented in cutaneous and ocular melanomas, little is known about PRAME protein expression in melanocytic tumors. In this study we examined the immunohistochemical expression of PRAME in 400 melanocytic tumors, including 155 primary and 100 metastatic melanomas, and 145 melanocytic nevi. Diffuse nuclear immunoreactivity for PRAME was found in 87% of metastatic and 83.2% of primary melanomas. Among melanoma subtypes, PRAME was diffusely expressed in 94.4% of acral melanomas, 92.5% of superficial spreading melanomas, 90% of nodular melanomas, 88.6% of lentigo maligna melanomas, and 35% of desmoplastic melanomas. When in situ and nondesmoplastic invasive melanoma components were present, PRAME expression was seen in both. Of the 140 cutaneous melanocytic nevi, 86.4% were completely negative for PRAME. Immunoreactivity for PRAME was seen, albeit usually only in a minor subpopulation of lesional melanocytes, in 13.6% of cutaneous nevi, including dysplastic nevi, common acquired nevi, traumatized/recurrent nevi, and Spitz nevi. Rare isolated junctional melanocytes with immunoreactivity for PRAME were also seen in solar lentigines and benign nonlesional skin. Our results suggest that immunohistochemical analysis for PRAME expression may be useful for diagnostic purposes to support a suspected diagnosis of melanoma. It may also be valuable for margin assessment of a known PRAME-positive melanoma, but its expression in nevi, solar lentigines, and benign nonlesional skin can represent a pitfall and merits further investigations to better assess the potential clinical utility of this marker.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Female; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Male; Melanocytes; Melanoma; Middle Aged; Nevus, Pigmented; Reproducibility of Results; Skin Neoplasms; Young Adult

PubMed: 30045064
DOI: 10.1097/PAS.0000000000001134

Authors: Elvira Moscarella, Pascale Guitera, Richard A Scolyer...

INTRODUCTION

Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi.

OBJECTIVES

This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi.

METHODS

From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal.

RESULTS

Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna.

CONCLUSIONS

Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.

PubMed: 36947065
DOI: 10.5826/dpc.1302a122

Authors: Arnaud de la Fouchardière, Daniel Pissaloux, Aurélie Houlier...

Fusion genes involving homologs of protein kinase C (PKC) have been identified in a variety of tumors. We report the clinical and histologic presentation of 51 cutaneous melanocytic neoplasms with a PKC fusion gene (involving PRKCA in 35 cases, PRKCB in 15 cases, and PRKCG in a single case). Most tumors were in young adults (median age, 29.5 years; range, 1-73 years) but some presented in newborns. Histologically, 42 tumors were classified as benign, presenting predominantly as biphasic dermal proliferation (88%) with nests of small melanocytes surrounded by fibrosis with haphazardly arranged spindled and dendritic melanocytes, resembling those reported as "combined blue nevi." Most tumors (60%) were heavily pigmented and in 15%, hyperpigmented epithelioid melanocytes were present at the dermoepidermal junction. Two lesions were paucicellular and showed marked sclerosis. Three tumors, including 2 proliferating nodules, were considered intermediate grade. Six tumors had sheets of atypical melanocytes infiltrating the dermis and were classified as melanomas. Two of the melanomas displayed loss of BAP1 nuclear expression. The median follow-up time was 12 months, with 1 patient alive with metastatic disease and 1 dying of their melanoma. These results suggest that melanocytic tumors with PKC fusion genes have characteristic histopathologic features, which are more similar to blue nevi than to pigmented epithelioid melanocytomas. As is the case with GNA-mutated blue nevi, they can progress to melanomas via BAP1 inactivation and metastasize.

Topics: Infant, Newborn; Young Adult; Humans; Adult; Nevus, Blue; Biomarkers, Tumor; Melanoma; Skin Neoplasms; Protein Kinase C

PubMed: 37474004
DOI: 10.1016/j.modpat.2023.100286

Attempting to Solve the Pigmented Epithelioid Melanocytoma (PEM) Conundrum: PRKAR1A Inactivation Can Occur in Different Genetic Backgrounds (Common, Blue, and Spitz Subgroups) With Variation in Their Clinicopathologic Characteristics.

Authors: Arnaud de la Fouchardiere, Franck Tirode, Christine Castillo...

Pigmented epithelioid melanocytoma is a rare cutaneous melanocytic proliferation considered high-grade melanocytoma in the 2018 WHO Classification of Skin Tumors. Little has been reported about the associated genetic drivers in addition to BRAF and MAP2K1 mutations or PRKCA gene fusions. Here, we present a series of 21 cases of PRKAR1A -inactivated melanocytic tumors in which we could assess the associated genetic background. We identified 9 different driver genes related to the common, Spitz, blue nevi, and PRKC -fused groups. Nine cases were associated with a canonical BRAF p.V600E mutation, a hallmark of the common nevus group. They occurred mainly in young adults. All were combined (biphenotypic) cases with a variable proportion of compound nevus. The pigmented epithelioid melanocytoma component was made of thin fascicules or isolated epithelioid cells covered by a dense hyperpigmented melanophage background and was predominantly located in the upper dermis. One such case was malignant. Six cases were associated with Spitz-related genetic anomalies ranging from HRAS or MAP2K1 mutations to gene fusions involving MAP3K8 , MAP3K3 , and RET . They occurred mainly in children and young adults. Morphologically, they showed large confluent junctional nests in a hyperplastic epidermis and a fascicular dermal component of spindled and epithelioid melanocytes with a frequent wedged silhouette. Intravascular invasion was observed in 4/6 cases. Five cases were associated with canonical mutations of the blue nevus group with 4 CYSLTR2 p.L129Q and 1 GNAQ p.Q209L mutations. They were removed mainly in adults and showed a frequent junctional component with epidermal hyperplasia. The dermal component showed dense fascicules of spindled and epithelioid melanocytes predominating over melanophages. One case occurred in a PRKCA -fused tumor in an adolescent with classic morphologic features. These results could potentially shift the concept of PRKAR1A -inactivated melanocytoma, changing from a rather unified model to a more complex one, including genetic subgroup variations with clinical and morphologic specificities. The genetic background of PRKAR1A -inactivated melanocytic tumors should be systematically explored to better understand the extent and clinical behavior of these complex lesions.

Topics: Adolescent; Child; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Genetic Background; Humans; Nevus; Nevus, Blue; Nevus, Epithelioid and Spindle Cell; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Young Adult

PubMed: 35319526
DOI: 10.1097/PAS.0000000000001888

Review

Scalp junctional nevus with malignant transformation (melanoma) metastatic to parotid lymph node region, cervical lymph nodes and the back: a case report and review of literature.

Authors: Zhuo-Ping Liang, Sheng-En Xu, Liang Jiang...

Parotid malignancy may occur as a primary neoplasm of the salivary tissue or as metastatic involvement of the parotid lymph nodes. Primary tumors of squamous cell carcinoma and malignant melanoma involving the skin of the head and neck have the potential to spread to lymph nodes of the parotid gland. Metastatic malignant melanoma to the back was exceptionally rare and no such reports have been noted in the literature. We reported an exceptional case of intraparotid lymph nodes metastasis of the right scalp junctional nevus with malignant transformation to malignant melanoma in a 48-year-old man. The patient presented with a mass in the parotid gland area, which was misdiagnosed as a primary parotid tumor and surgical removal was performed. Unfortunately, recurrence with newly developed metastatic lesions in the back and cervical lymph nodes occurred 1 year after initial surgical management. This case is presented highlighting the unusual features of metastatic junctional nevus with malignant transformation to malignant melanoma of intraparotid lymph nodes, cervical lymph nodes and the back, which should help us to reduce misdiagnosis and obtain the best results.

Topics: Cell Transformation, Neoplastic; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Nevus, Pigmented; Parotid Neoplasms; Scalp; Skin Neoplasms

PubMed: 25755802
DOI: No ID Found

Authors: Yumei Lai, Yan Wu, Ruping Liu...

BACKGROUND/OBJECTIVE

Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma.

METHODS

Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion.

RESULTS

Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami's criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami's or Gaiser's criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma.

CONCLUSIONS

We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; In Situ Hybridization, Fluorescence; Male; Melanoma; Middle Aged; Nevus, Pigmented; Skin Neoplasms; Young Adult

PubMed: 32393283
DOI: 10.1186/s13000-020-00937-9

Authors: Cristina L Saratxaga, Aintzane Asumendi, Jesús Gardeazabal...

BACKGROUND

Melanoma incidence has continued to rise in the latest decades, and the forecast is not optimistic. Non-invasive diagnostic imaging techniques such as optical coherence tomography (OCT) are largely studied; however, there is still no agreement on its use for the diagnosis of melanoma. For dermatologists, the differentiation of non-invasive (junctional nevus, compound nevus, intradermal nevus, and melanoma in-situ) versus invasive (superficial spreading melanoma and nodular melanoma) lesions is the key issue in their daily routine.

METHODS

This work performs a comparative analysis of OCT images using haematoxylin-eosin (HE) and anatomopathological features identified by a pathologist. Then, optical and textural properties are extracted from OCT images with the aim to identify subtle features that could potentially maximize the usefulness of the imaging technique in the identification of the lesion's potential invasiveness.

RESULTS

Preliminary features reveal differences discriminating melanoma in-situ from superficial spreading melanoma and also between melanoma and nevus subtypes that pose a promising baseline for further research.

CONCLUSIONS

Answering the final goal of diagnosing non-invasive versus invasive lesions with OCT does not seem feasible in the short term, but the obtained results demonstrate a step forward to achieve this.

PubMed: 36983781
DOI: 10.3390/life13030625

Authors: Rafaella Daboit Castagna, Juliana Mazzoleni Stramari, Raíssa Massaia Londero Chemello...

Recurrent melanocytic nevus is a proliferation of melanocytes arising from a melanocytic nevus removed partially. Asymmetry and irregular pigmentation may lead to misdiagnosis of melanoma. We report a patient presented with a lesion on the lower abdomen, which was removed by shave excision. Anatomopathological examination revealed an intradermal melanocytic nevus. Two months later, a new irregular hyperpigmented lesion appeared in the surgical scar. Histopathology of the excisional biopsy revealed a recurrent melanocytic nevus. Recurrent melanocytic nevus manifests as a scar with hyper or hypopigmented areas, linear streaking, stippled pigmented halos, and/or diffuse pigmentation patterns. Histologically, the dermoepidermal junction and the superficial dermis show melanocytic proliferation overlying the scarred area. When a pathological report of the previous lesion is not available, complete excision is the gold standard. Otherwise, regular dermoscopic monitoring is a therapeutic option. The present report emphasizes the importance of histopathological examination of the excised material - even in cases of suspected benign lesions - and warns patients about the possibility of recurrence in case of incompletely removed lesions.

Topics: Biopsy; Cell Proliferation; Dermoscopy; Female; Humans; Melanocytes; Middle Aged; Neoplasm Recurrence, Local; Nevus, Pigmented; Skin Neoplasms

PubMed: 28954104
DOI: 10.1590/abd1806-4841.20176190