The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red–purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.
{"title":"Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls","authors":"Yushi Kanatani, Yasuhiro Mitsui, Kohei Ogawa, Maiko Takeda, Fumi Miyagawa, Satoru Shinkuma, Takeshi Kawaguchi, Takaya Fukumoto, Hideo Asada","doi":"10.1111/cup.14614","DOIUrl":"10.1111/cup.14614","url":null,"abstract":"<p>The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red–purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Onychomatricoma is not a subtype of superficial acral fibromyxoma: Can immunohistochemistry help in the differential diagnosis?","authors":"Christophe Perrin MD, Michael Coutts MD","doi":"10.1111/cup.14616","DOIUrl":"10.1111/cup.14616","url":null,"abstract":"","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina H. Cheng BS, David Smith DO, Carla Errickson MD, Shaymaa Ashi MD
Granular cell tumors (GCTs) are rare, indolent neoplasms classically characterized by eosinophilic granular cytoplasm, infiltrations of polygonal cells in the collagenous stroma, and pustulo-ovoid bodies of Milian. We describe a case of a 10-year-old female presenting with a GCT of the upper arm, remarkable for positive Melan-A expression without additional melanocytic features. The differentiation between granular cells versus melanocytic neoplasms carries significant implications for clinical management, and such diagnoses should be considered carefully in the setting of unusual immunophenotypes.
{"title":"A rare case of cutaneous granular cell tumor with unusual Melan-A expression in a child","authors":"Nina H. Cheng BS, David Smith DO, Carla Errickson MD, Shaymaa Ashi MD","doi":"10.1111/cup.14619","DOIUrl":"10.1111/cup.14619","url":null,"abstract":"<p>Granular cell tumors (GCTs) are rare, indolent neoplasms classically characterized by eosinophilic granular cytoplasm, infiltrations of polygonal cells in the collagenous stroma, and pustulo-ovoid bodies of Milian. We describe a case of a 10-year-old female presenting with a GCT of the upper arm, remarkable for positive Melan-A expression without additional melanocytic features. The differentiation between granular cells versus melanocytic neoplasms carries significant implications for clinical management, and such diagnoses should be considered carefully in the setting of unusual immunophenotypes.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term “primary cutaneous marginal zone LPD,” in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.
20 世纪 80 年代,免疫组化和克隆性分析在识别和定义新类型的皮肤 T 细胞淋巴瘤(CTCL)和皮肤 B 细胞淋巴瘤(CBCL)以及制定新的分类标准方面发挥了重要作用。通过接受泛T细胞抗原缺失和克隆T细胞受体基因重排作为区分良性和恶性T细胞增生的重要标准,以及接受单型免疫球蛋白轻链表达和克隆免疫球蛋白基因重排作为区分良性和恶性B细胞增生的重要标准,许多病例在此之前被诊断为皮肤T细胞淋巴瘤(CTCL)和皮肤B细胞淋巴瘤(CBCL)、在此之前,许多被诊断为皮肤淋巴样增生或假淋巴瘤的病例被重新分类为原发性皮肤 CD4+ 小/中 T 细胞淋巴瘤(PCSM-TCL)或原发性皮肤边缘区淋巴瘤(PCMZL)。然而,近年来人们越来越认识到,无论是这些免疫组化标准,还是 T 细胞或 B 细胞克隆性的证明,都不是恶性淋巴瘤的特异性标准。此外,许多研究报告称,这些低度恶性 CTCL 和 CBCL 临床表现不明显,预后良好,疾病特异性生存率达到或接近 100%。因此,最近的分类将几种低度恶性皮肤淋巴瘤降级为淋巴增生性疾病(LPD)。第五版世卫组织分类(2022 年)和 2022 年成熟淋巴肿瘤国际共识分类(ICC)都将 PCSM-TCL 重新分类为原发性皮肤 CD4+ 小/中 T 细胞淋巴增生性疾病,将原发性皮肤尖锐湿疣 CD8+ T 细胞淋巴瘤重新分类为原发性皮肤尖锐湿疣 CD8+ T 细胞淋巴增生性疾病。2022 年 ICC 引入了 "原发性皮肤边缘区 LPD "这一术语,而在第五版世界卫生组织分类中则保留了 PCMZL。在这篇综述中,我们描述了这些疾病术语不断变化的背景和原因,并讨论了将恶性淋巴瘤降级为 LPD 的临床后果。
{"title":"Cutaneous lymphoproliferative disorders: Back to the future","authors":"Rein Willemze MD","doi":"10.1111/cup.14609","DOIUrl":"10.1111/cup.14609","url":null,"abstract":"<p>In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term “primary cutaneous marginal zone LPD,” in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed Shah MD, MSc, Adrian Box MD, PhD, Thomas Brenn MD, PhD, Ashley Flaman MD
Nuclear protein in testis (NUT) carcinoma, molecularly defined by the NUTM1 gene rearrangement, is most commonly reported in young adults in the sinonasal tract, nasopharynx, or thorax. At these sites, NUT carcinoma is an extremely aggressive malignancy with dismal prognosis. Recently, five cases of primary cutaneous NUT adnexal carcinoma have been reported with BRD3 and NSD3 fusion partners. Although NUT adnexal carcinomas are shown to have metastatic potential, they may behave less aggressively than extracutaneous NUT carcinomas. We report a case of a 59-year-old man who underwent a biopsy of a 3-cm plantar mass, which showed BRD4::NUTM1 fusion. The tumor was a poorly differentiated dermal neoplasm showing cytologic atypia, large vesicular nuclei with prominent nucleoli, conspicuous mitotic activity, and foci of necrosis. Immunohistochemically, the tumor showed positivity for keratins, EMA, SOX10, and NUT, with patchy smooth muscle actin. Molecular testing revealed BRD4::NUTM1 rearrangement. With no alternative primary identified by imaging, a diagnosis of primary cutaneous NUT carcinoma was favored. We hope to contribute to the limited body of knowledge on this entity, with emphasis on recognition as well as studying and defining its prognostic differences from extracutaneous NUT carcinomas.
{"title":"Primary cutaneous NUT carcinoma with BRD4::NUTM1 fusion","authors":"Ahmed Shah MD, MSc, Adrian Box MD, PhD, Thomas Brenn MD, PhD, Ashley Flaman MD","doi":"10.1111/cup.14602","DOIUrl":"10.1111/cup.14602","url":null,"abstract":"<p>Nuclear protein in testis (NUT) carcinoma, molecularly defined by the <i>NUTM1</i> gene rearrangement, is most commonly reported in young adults in the sinonasal tract, nasopharynx, or thorax. At these sites, NUT carcinoma is an extremely aggressive malignancy with dismal prognosis. Recently, five cases of primary cutaneous NUT adnexal carcinoma have been reported with <i>BRD3</i> and <i>NSD3</i> fusion partners. Although NUT adnexal carcinomas are shown to have metastatic potential, they may behave less aggressively than extracutaneous NUT carcinomas. We report a case of a 59-year-old man who underwent a biopsy of a 3-cm plantar mass, which showed <i>BRD4::NUTM1</i> fusion. The tumor was a poorly differentiated dermal neoplasm showing cytologic atypia, large vesicular nuclei with prominent nucleoli, conspicuous mitotic activity, and foci of necrosis. Immunohistochemically, the tumor showed positivity for keratins, EMA, SOX10, and NUT, with patchy smooth muscle actin. Molecular testing revealed <i>BRD4::NUTM1</i> rearrangement. With no alternative primary identified by imaging, a diagnosis of primary cutaneous NUT carcinoma was favored. We hope to contribute to the limited body of knowledge on this entity, with emphasis on recognition as well as studying and defining its prognostic differences from extracutaneous NUT carcinomas.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gene fusions have emerged as crucial molecular drivers of oncogenesis in a subset of cutaneous adnexal neoplasms, including poroid neoplasms and hidradenomas. We present a unique case of primary cutaneous apocrine carcinoma harboring RARA::NPEPPS fusion, broadening the spectrum of fusion-associated cutaneous adnexal neoplasms. A 77-year-old African American male presented with an ulcerated thigh nodule. Histopathologically, the predominantly dermal-based adenocarcinoma exhibited papillary, micropapillary, cribriform, and solid growth patterns with central comedonecrosis, set in a fibrotic/desmoplastic stroma. Immunophenotypically, the neoplastic cells were positive for CK7, CK19, GATA3, TRPS1, HER2, CK5/6, calretinin, p63, and DPC4 (no loss), while lacking immunoreactivity for CK20, CDX2, TTF1, napsin-A, PAX8, arginase-1, adipophilin, NKX3.1, uroplakin II, and D2-40. The immunoprofile and clinical and radiographic absence of any internal malignancy, including breast carcinoma, except for multiple lymphadenopathy, supported the diagnosis of primary cutaneous apocrine carcinoma. Next-generation sequencing unveiled the novel RARA::NPEPPS fusion, concurrent ERBB2 amplification, and multiple somatic mutations involving TP53, CDKN2A, BRCA2, PIK3CA, PIK3R1, and others. The patient developed widespread metastases within a year after the initial diagnosis, indicating the tumor's aggressive behavior. This novel fusion, unprecedented in any human malignancies including primary cutaneous adnexal carcinomas, may suggest a potential new subtype within primary cutaneous adnexal carcinoma.
{"title":"Primary cutaneous apocrine carcinoma with RARA::NPEPPS fusion","authors":"Volha Lenskaya, Richard K. Yang, Woo Cheal Cho","doi":"10.1111/cup.14607","DOIUrl":"10.1111/cup.14607","url":null,"abstract":"<p>Gene fusions have emerged as crucial molecular drivers of oncogenesis in a subset of cutaneous adnexal neoplasms, including poroid neoplasms and hidradenomas. We present a unique case of primary cutaneous apocrine carcinoma harboring <i>RARA::NPEPPS</i> fusion, broadening the spectrum of fusion-associated cutaneous adnexal neoplasms. A 77-year-old African American male presented with an ulcerated thigh nodule. Histopathologically, the predominantly dermal-based adenocarcinoma exhibited papillary, micropapillary, cribriform, and solid growth patterns with central comedonecrosis, set in a fibrotic/desmoplastic stroma. Immunophenotypically, the neoplastic cells were positive for CK7, CK19, GATA3, TRPS1, HER2, CK5/6, calretinin, p63, and DPC4 (no loss), while lacking immunoreactivity for CK20, CDX2, TTF1, napsin-A, PAX8, arginase-1, adipophilin, NKX3.1, uroplakin II, and D2-40. The immunoprofile and clinical and radiographic absence of any internal malignancy, including breast carcinoma, except for multiple lymphadenopathy, supported the diagnosis of primary cutaneous apocrine carcinoma. Next-generation sequencing unveiled the novel <i>RARA::NPEPPS</i> fusion, concurrent <i>ERBB2</i> amplification, and multiple somatic mutations involving <i>TP53</i>, <i>CDKN2A</i>, <i>BRCA2</i>, <i>PIK3CA</i>, <i>PIK3R1</i>, and others. The patient developed widespread metastases within a year after the initial diagnosis, indicating the tumor's aggressive behavior. This novel fusion, unprecedented in any human malignancies including primary cutaneous adnexal carcinomas, may suggest a potential new subtype within primary cutaneous adnexal carcinoma.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrés Grau-Echevarría MD, Carolina Labrandero-Hoyos MD, Rodrigo Peñuelas-Leal MD, Malena Finello MD, Daniel Blaya-Imbernón MD, José Ángel García-García MD, PhD, María Dolores Berenguer-Romero MD, Víctor Alegre de Miquel MD, PhD, Amparo Pérez-Ferriols MD, PhD, Pablo Martínez-Calabuig MD, Pablo Hernández-Bel MD, PhD
Anetoderma or macular atrophy is a rare skin condition of unclear pathogenesis, often associated with autoimmune diseases and skin damage from various infections. Human immunodeficiency virus (HIV), syphilis, and poxviruses have been implicated in the development of anetoderma. A 37-year-old male patient with HIV and recent unprotected sexual encounters presented with more than 400 skin lesions, consistent with Mpox. Symptomatic treatment for Mpox resulted in acute symptom resolution. However, 8 months later he developed papular anetoderma lesions in areas previously affected by Mpox. Biopsy confirmed the loss of elastic fibers in the affected skin areas, leading to the diagnosis of Mpox-induced anetoderma. This report presents a unique case of anetoderma following Mpox in an HIV-positive patient.
{"title":"Anetoderma after disseminated Mpox","authors":"Andrés Grau-Echevarría MD, Carolina Labrandero-Hoyos MD, Rodrigo Peñuelas-Leal MD, Malena Finello MD, Daniel Blaya-Imbernón MD, José Ángel García-García MD, PhD, María Dolores Berenguer-Romero MD, Víctor Alegre de Miquel MD, PhD, Amparo Pérez-Ferriols MD, PhD, Pablo Martínez-Calabuig MD, Pablo Hernández-Bel MD, PhD","doi":"10.1111/cup.14606","DOIUrl":"10.1111/cup.14606","url":null,"abstract":"<p>Anetoderma or macular atrophy is a rare skin condition of unclear pathogenesis, often associated with autoimmune diseases and skin damage from various infections. Human immunodeficiency virus (HIV), syphilis, and poxviruses have been implicated in the development of anetoderma. A 37-year-old male patient with HIV and recent unprotected sexual encounters presented with more than 400 skin lesions, consistent with Mpox. Symptomatic treatment for Mpox resulted in acute symptom resolution. However, 8 months later he developed papular anetoderma lesions in areas previously affected by Mpox. Biopsy confirmed the loss of elastic fibers in the affected skin areas, leading to the diagnosis of Mpox-induced anetoderma. This report presents a unique case of anetoderma following Mpox in an HIV-positive patient.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haneen T. Salah, Richard K. Yang, Sinchita Roy-Chowdhuri, Merrick I. Ross, Phyu P. Aung, Aimi T. Rothrock, Carlos A. Torres-Cabala, Jonathan L. Curry, Victor G. Prieto, Priyadharsini Nagarajan, Woo Cheal Cho
ALK-fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform-to-epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the ALK gene have been identified in spitzoid melanocytic neoplasms, with TPM3 and DCTN1 being the most prevalent. Less common fusion partners include NPM1, TPR, CLIP1, GTF3C2, EEF2, MYO5A, KANK1, and EHBP1. The MLPH gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of ALK in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring MLPH::ALK fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on ALK-fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion.
{"title":"Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review","authors":"Haneen T. Salah, Richard K. Yang, Sinchita Roy-Chowdhuri, Merrick I. Ross, Phyu P. Aung, Aimi T. Rothrock, Carlos A. Torres-Cabala, Jonathan L. Curry, Victor G. Prieto, Priyadharsini Nagarajan, Woo Cheal Cho","doi":"10.1111/cup.14605","DOIUrl":"10.1111/cup.14605","url":null,"abstract":"<p><i>ALK</i>-fused Spitz melanocytic neoplasms are a distinct subgroup of melanocytic lesions exhibiting unique histopathologic characteristics. These lesions often manifest as exophytic or polypoid tumors, characterized by fusiform-to-epithelioid melanocytes arranged in a nested, fascicular, or plexiform growth pattern. Several fusion partners of the <i>ALK</i> gene have been identified in spitzoid melanocytic neoplasms, with <i>TPM3</i> and <i>DCTN1</i> being the most prevalent. Less common fusion partners include <i>NPM1</i>, <i>TPR</i>, <i>CLIP1</i>, <i>GTF3C2</i>, <i>EEF2</i>, <i>MYO5A</i>, <i>KANK1</i>, and <i>EHBP1</i>. The <i>MLPH</i> gene, which encodes melanophilin (MLPH), playing a crucial role in regulating skin pigmentation by acting as a linker between RAB27A and myosin Va during melanosome transport, has also recently been recognized as a rare fusion partner of <i>ALK</i> in Spitz melanocytic neoplasms. Currently, there exists a sparse documentation within English literature, illustrating a limited number of cases featuring <i>MLPH::ALK</i> fusion in Spitz melanocytic neoplasms. In this report, we present two additional cases, including a previously unreported instance of Spitz melanoma, contributing to the expanding knowledge on <i>ALK</i>-fused Spitz melanocytic neoplasms. In addition, we provide a comprehensive review of the clinical, histopathologic, and molecular features observed in documented cases with this novel fusion.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}