RESUMO
ABSTRACT: Spitz tumors are melanocytic neoplasms characterized by specific, mutually exclusive driver molecular events, namely genomic rearrangements involving the threonine kinase BRAF and the tyrosine kinase receptors ALK , NTRK1 , NTRK2 , NTRK3 , MET , RET , ROS1 , and MAP3K8 or less commonly, mutations in HRAS or MAP2K1 . We hereby report 5 Spitz tumors with a SQSTM1::NTRK2 fusion. All patients were woman with the ages at diagnosis ranging from 30 to 50 years. Locations included the lower extremity (n = 3), forearm, and back (one each). All the neoplasms were superficial melanocytic proliferation with a flat to dome-shaped silhouette, in which junctional spindled and polygonal dendritic melanocytes were mainly arranged as horizontal nests associated with conspicuous lentiginous involvement of the follicular epithelium. Only one case showed heavily pigmented, vertically oriented melanocytic nests resembling Reed nevus. A superficial intradermal component observed in 2 cases appeared as small nests with a back-to-back configuration. In all lesions, next-generation sequencing analysis identified a SQSTM1::NTRK2 fusion. A single case studied with fluorescence in situ hybridization for copy number changes in melanoma-related genes proved negative. No further molecular alterations were detected, including TERT-p hotspot mutations.
Assuntos
Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Proteína Sequestossoma-1/genética , Proteínas Tirosina Quinases/genética , Nevo de Células Epitelioides e Fusiformes/genética , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genéticaRESUMO
BAP1-inactivated melanocytic tumor (BIMT) is a group of melanocytic neoplasms with epithelioid cell morphology molecularly characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, and a mutually exclusive mitogenic driver mutation, more commonly BRAF. BIMTs can occur as a sporadic lesion or, less commonly, in the setting of an autosomal dominant cancer susceptibility syndrome caused by a BAP1 germline inactivating mutation. Owing to the frequent identification of remnants of a conventional nevus, BIMTs are currently classified within the group of combined melanocytic nevi. "Pure" lesions can also be observed. We studied 50 BIMTs from 36 patients. Most lesions were composed of epithelioid melanocytes of varying size and shapes, resulting extreme cytomorphological heterogeneity. Several distinctive morphological variants of multinucleated/giant cells were identified. Some hitherto underrecognized microscopic features, especially regarding nuclear characteristics included nuclear blebbing, nuclear budding, micronuclei, shadow nuclei, peculiar cytoplasmic projections (ant-bear cells) often containing micronuclei and cell-in-cell structures (entosis). In addition, there were mixed nests of conventional and BAP1-inactivated melanocytes and squeezed remnants of the original nevus. Of the 26 lesions studied, 24 yielded a BRAF mutation, while in the remaining two cases there was a RAF1 fusion. BAP1 biallelic and singe allele mutations were found in 4/22 and 16/24 neoplasms, respectively. In five patients, there was a BAP1 germline mutation. Six novel, previously unreported BAP1 mutations have been identified. BAP1 heterozygous loss was detected in 11/22 lesions. Fluorescence in situ hybridization for copy number changes revealed a related amplification of both RREB1 and MYC genes in one tumor, whereas the remaining 20 lesions studied were negative; no TERT-p mutation was found in 14 studied neoplasms. Tetraploidy was identified in 5/21 BIMTs. Of the 21 patients with available follow-up, only one child had a locoregional lymph node metastasis. Our results support a progression of BIMTs from a conventional BRAF mutated in which the original nevus is gradually replaced by epithelioid BAP1-inactivated melanocytes. Some features suggest more complex underlying pathophysiological events that need to be elucidated.
Assuntos
Nevo de Células Epitelioides e Fusiformes , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Criança , Humanos , Hibridização in Situ Fluorescente , Nevo de Células Epitelioides e Fusiformes/genética , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
Long regarded as ectopic or supernumerary breast tissue, anogenital mammary-like glands (AGMLG) are now considered a normal constituent of the anogenital area. AGMLG are presumed to be the origin for various benign and malignant lesions. Changes in AGMLG compatible with usual ductal hyperplasia and atypical ductal hyperplasia considered as precursor lesions and its presence in specimens can be explained by their role in the pathogenesis of primary extramammary Paget disease. In this report, we presented four cases of invasive squamous cell carcinoma accompanied by non-neoplastic atypical changes in ductal portions of AGMLG compatible with atypical ductal hyperplasia in breast adjacent to the carcinoma. This is a reactive phenomenon similar to that seen in apocrine/eccrine glands adjacent to squamous cell carcinoma. In a limited biopsy specimen, these areas should not be mistaken for adenocarcinoma.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma de Células Escamosas/patologia , Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Idoso , Idoso de 80 Anos ou mais , Glândulas Apócrinas/patologia , Mama/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Períneo/patologia , Vulva/patologia , Neoplasias Vulvares/cirurgiaRESUMO
ABSTRACT: Trichoblastoma (TB) is a benign biphasic follicular neoplasm with differentiation toward the germinative cells and a specific follicular mesenchyme. We subtyped 349 sporadic TB according to a classification proposed by Ackerman. Two hundred forty-six (246/349, 70.5%) neoplasms were comprised of mixed subtypes. TB composed exclusively of a single pattern was less common (103/349, 29.5%). The most common pure subtype was cribriform TB followed by small nodular TB. Twelve cases (12/349, 3.4%) had unique features and are reported herein as novel histopathologic subtypes of the neoplasm.
Assuntos
Doenças do Cabelo/patologia , Folículo Piloso/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ABSTRACT: Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.
Assuntos
Adenoma/metabolismo , Adenoma/patologia , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias das Glândulas Sebáceas/metabolismo , Neoplasias das Glândulas Sebáceas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Extremidades , Face , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Couro Cabeludo , Tronco , Adulto JovemRESUMO
ABSTRACT: Primary cutaneous desmoplastic melanoma (DM) is a group of rare melanocytic tumors arising on severely sun-damaged skin, histologically characterized by the proliferation of spindled melanocytes in a prominent desmoplastic stroma, with a range of morphological presentations. In this article, we report a unique case of primary cutaneous DM composed of a nodular proliferation of highly pleomorphic spindled and epithelioid cells, pseudoglandular structures, clear cell change, and unusual collagen rosettes. Immunohistochemical analysis showed a strong and diffuse positivity for S-100 protein, SOX-10, nestin, p75 (nerve growth factor receptor), WT1, and p53. Molecular analysis detected a mutation in the NF1 gene [c.4084C > T, p.(Arg1362Ter)], 2 different pathogenic mutations in TP53 [c.742C > T, p.(Arg248Trp), AF:12%, COSM1640831 and c.528C > G, p.(Cys176Trp), AF:12%, COSM11114], and a mutation in GNAS [c.601C > T, p.(Arg201Cys), AF: 9%, COSM123397]. To the best of our knowledge, this is the first case reporting collagen rosettes and pseudoglandular features in primary cutaneous DM.
Assuntos
Colágeno Tipo IV/metabolismo , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Imuno-Histoquímica , Masculino , Melanoma/metabolismo , Mutação , Neurofibromina 1/genética , Neoplasias Cutâneas/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
ABSTRACT: Specific alterations involving MAPK genes (MAP3K8 fusions, MAP3K3 fusions) have been recently detected in a subgroup of spitzoid neoplasms that seem to constitute a distinctive clinicopathologic group, occur mostly in younger patients (median age 18 years) and present with atypical histologic features associated with frequent homozygous deletion of CDKN2A, qualifying a high proportion of them as Spitz melanoma (malignant Spitz tumor). Apart from lesions with spitzoid morphology harboring MAP3K8 or MAP3K3 fusion, a single case with MAP2K1 deletion has been identified. The authors report herein 4 melanocytic lesions with a MAP2K1 mutation, all showing similar microscopic appearances, including spitzoid cytology and dysplastic architectural features, resembling so-called SPARK nevus, suggesting that these lesions may represent another distinctive group.
Assuntos
MAP Quinase Quinase 1/genética , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genéticaRESUMO
We report a case of a polypoid atypical Spitz tumor with a prominent fibrosclerotic stromal component, harboring a CLIP2-BRAF fusion, which has hitherto been not reported in melanocytic lesions. The neoplasm occurred in a 78-year-old male patient and appeared microscopically as a predominantly dermal, barely symmetrical, polypoid lesion composed mainly of epithelioid cells showing moderate degree of nuclear pleomorphism with ample amphophilic cytoplasm arranged in nests, fascicles, or single units. The mitotic rate was 2/mm, and the mitoses were confined to the upper portion of the lesion. The Breslow thickness was 2.3 mm. The stroma contained conspicuous plumped fibroblasts and thickened collagen bundles associated with dilated medium-sized vessels. Focally, sclerotic areas were found. A moderately dense, lymphocyte-predominant inflammatory infiltrate scattered through the whole lesion was seen. Despite strong nuclear and cytoplasmic positivity of p16, FISH revealed homozygous loss in locus 9p21. A CLIP2-BRAF fusion was found by next-generation sequencing. No other genetic alterations including a TERT-promoter mutation was found. The patient is disease-free without recurrence or evidence of metastatic disease after 5 years and 2 months of follow-up.
Assuntos
Nevo de Células Epitelioides e Fusiformes/genética , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 9/genética , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Fusão Oncogênica , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Intralymphatic histiocytosis is a rare reactive skin condition characterized by a nonspecific clinical presentation and, microscopically, by the collections of mononuclear histiocytes within the lumina of dilated lymphatic vessels. We report a rare case of intralymphatic histiocytosis associated with rosacea and prominent periocular edema (Morbihan disease). The patient is a 56-year-old woman with a 12-year history of rosacea who suddenly developed edema of the right upper eyelid that persisted 6 months before she sought medical advice. Because of an unclear clinical diagnosis, surgical excision of the edematous upper eyelid was performed. The histologic slides showed interstitial edema of the dermis with dilated vascular channels and small epithelioid cell granulomas around hair follicles. In addition, there were aggregates of cells inside numerous lymphatic vessels that were immunohistochemically positive for CD45, CD4, CD68, CD163, CD64, CD14, CD11c, and lysozyme and negative for CD3, CD20, CD30, CD56, S100, CD1a, and langerin.
Assuntos
Doenças Palpebrais/patologia , Histiocitose/patologia , Vasos Linfáticos/patologia , Rosácea/complicações , Doenças Palpebrais/complicações , Feminino , Histiocitose/complicações , Humanos , Pessoa de Meia-IdadeRESUMO
Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma characterized by a malignant serous effusion involving body cavities. It usually associated with human herpes virus-8 (HHV-8) and coexpression of Epstein-Barr virus and mostly affects patients with HIV. We report a rare case of cutaneous PEL with an unusual intravascular presentation, combined with Kaposi sarcoma involving the skin, lung, and gastrointestinal tract. The molecular genetic analysis of the sarcoma and lymphoma components, using next-generation sequencing was performed. The patient was a 67-year-old man who presented with multiple cutaneous tumors and mass in the left lung. He died 17 hours after the admission to the hospital. At autopsy, in addition to the cutaneous lesions, tumors in the left lung and gastrointestinal mucosa were detected, and no effusions in the body cavities were seen. The biopsy from the cutaneous lesions, pulmonary, and intestinal tumors revealed histological and immunohistochemical features of Kaposi sarcoma. In addition, the skin biopsy specimens contained a diffuse infiltrate composed of large pleomorphic cells, with focal intravascular growth that were negative for pan B-cell markers, weakly positive for CD38 and CD138 but expressed CD3, HHV-8, and Epstein-Barr virus. Molecular genetic studies in this specimen revealed monoclonal rearrangements of the IgH gene. The diagnosis of PEL, solid variant, was made. Next-generation sequencing analysis of the tumorous and normal tissue detected a pathogenic germline mutation of the FAM175A gene and somatic mutations in BRCA2 and RAD51B (in both sarcoma and lymphoma specimens), and INPP4B and RICTOR (in lymphoma specimen only).
Assuntos
Proteínas de Transporte/genética , Linfoma de Efusão Primária/patologia , Sarcoma de Kaposi/patologia , Idoso , Mutação em Linhagem Germinativa , Humanos , Linfoma de Efusão Primária/complicações , Linfoma de Efusão Primária/genética , Masculino , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/genéticaRESUMO
Pigmented epithelioid melanocytoma is a highly pigmented, predominantly dermal melanocytic neoplasm composed by epithelioid and spindled melanocytes. It is characterized by a limited number of specific genomic alterations principally involving protein kinase A regulatory subunit alpha (PRKAR1A) and fusion of protein kinase C alpha isoform (PRKCA). However, in some of these neoplasms, no genetic aberrations have been detected. We performed genomic analysis of a nodular heavily pigmented intradermal proliferation composed of monomorphic epithelioid melanocytes with slight cytologic atypia consisting with pigmented epithelioid melanocytoma occurring on the vulva of a 24-year-old woman. A novel fusion transcript HTT-PKN1 and an ATM (Val410Ala) missense mutation were found. No other mutations including TERT-promoter hotspot mutation analysis were detected. The data expand the spectrum of molecular alterations in pigmented epithelioid melanocytoma.
Assuntos
Melanoma/genética , Melanoma/patologia , Neoplasias Vulvares/genética , Neoplasias Vulvares/patologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Células Epitelioides/patologia , Feminino , Humanos , Proteína Huntingtina/genética , Melanócitos/patologia , Mutação de Sentido Incorreto , Fusão Oncogênica , Proteína Quinase C/genéticaRESUMO
BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) is a group of epithelioid melanocytic neoplasms characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21. They occur sporadically or in the setting of an autosomal-dominant cancer susceptibility syndrome that predisposes to the development of different internal malignancies. Most of these cutaneous lesions are associated with a BRAF-mutated melanocytic nevus and therefore are included in the group of combined nevi in the last WHO classification of skin tumors. Apart from a BRAF mutation, an NRAS mutation has been reported in rare cases, whereas in some lesions no driver mutation has been detected. Here, we report 2 cases of BIMTs with a BAP1 mutation and a RAF1 fusion. Both lesions proved to be BRAF and NRAS wild type and were associated with a conventional melanocytic nevus with dysplastic junctional features. We suggest that RAF1 fusions can represent an underlying driver genetic event in these cases. Our study extends the morphological and molecular spectrum in BIMTs.
Assuntos
Biomarcadores Tumorais/genética , Fusão Gênica , Inativação Gênica , Nevo Pigmentado/genética , Proteínas Proto-Oncogênicas c-raf/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adulto , Biomarcadores Tumorais/análise , Criança , Análise Mutacional de DNA , Feminino , GTP Fosfo-Hidrolases/genética , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Nevo Pigmentado/química , Nevo Pigmentado/patologia , Nevo Pigmentado/cirurgia , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
Spitz tumors represent a heterogeneous group of melanocytic neoplasms with a spectrum of biological behavior ranging from benign (Spitz nevus) to malignant (spitzoid melanoma). Prediction of the behavior of these lesions based on their histological presentation is not always possible. Recently, mutually exclusive activating kinase fusions, involving ALK, NTRK1, NTRK3, RET, MET, ROS1, and BRAF, have been found in a subset of spitzoid lesions. Some of these genetic alterations were associated with specific morphological features. Here, we report the histological presentation of 6 Spitz tumors with ROS1 fusion. The age of the patients ranged from 6 to 34 years, with strong female prevalence (5:1). All neoplasms were compound melanocytic proliferations with a predominant dermal growth but a conspicuous junctional component displaying atypical microscopic features qualifying them as atypical Spitz tumor. FIP1L1 and CAPRIN1 were identified as 2 novel 5'-fusion partners of ROS1 along with the known PWWP2A-ROS1 fusion. FISH for copy number changes of 9p21, 6p25, and 11q13 was negative in all but 1 neoplasm harboring isolated gain of 8q24. TERT-promoter hotspot mutation analysis was negative in all tumors. All patients are disease-free after a mean follow-up period of 30 months. It is concluded that ROS1-fused spitzoid neoplasms seem to have no distinctive histopathological features although consistent findings were spindled melanocytes arranged in confluent whorling nests, prominent transepidermal elimination of melanocytic nests, and myxoid/mucinous changes.
Assuntos
Melanoma/genética , Nevo de Células Epitelioides e Fusiformes/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Proteínas de Ciclo Celular/genética , Criança , Proteínas Cromossômicas não Histona/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Fusão Oncogênica , Neoplasias Cutâneas/patologia , Telomerase/genética , Adulto Jovem , Fatores de Poliadenilação e Clivagem de mRNA/genéticaRESUMO
Specific cutaneous involvement in Hodgkin lymphoma is rare. In cutaneous lesions, the diagnosis is usually based on the recognition of diagnostic Reed-Sternberg cells and its variants. In nodal Hodgkin lymphoma, so-called mummified cells (cells with condensed cytoplasm and pyknotic eosinophilic or basophilic nuclei) are often seen. They are sometimes conspicuous and easy to recognize, thus serving as a clue to the diagnosis. Our objective was to study cases of cutaneous Hodgkin lymphoma to identify the occurrence of mummified cells. We studied 12 patients (4 women and 8 men; age range 23-80 years). In 6 patients, cutaneous and extracutaneous disease was identified almost simultaneously; in 4 patients, lymph node disease preceded cutaneous involvement; and in the remaining 2 patients, the skin lesions were the presenting sign, whereas lymph node involvement occurred later. Histopathological, immunohistochemical, and molecular-genetic studies, including rearrangements for TCR, IgH genes, and PCR for EBV, were performed. Cutaneous biopsy specimens revealed either a multinodular or diffuse infiltrate, included small lymphocytes, eosinophils, plasma cells, and macrophages, but in all cases, diagnostic Reed-Sternberg cells and its variants were identified. Mummified cells were detected in 9 cases, either as occasional scattered mummified cells often requiring a search (6 cases) or being conspicuous, grouped and therefore easily identified (3 cases). Immunohistochemically, in all 7 cases studied, mummified cells were positive for both CD30 and CD15. It is concluded that mummified cells are encountered in a majority of cases of cutaneous Hodgkin lymphoma.
Assuntos
Doença de Hodgkin/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.
Assuntos
Quinase do Linfoma Anaplásico/genética , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Telomerase/genética , Adolescente , Adulto , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Análise Mutacional de DNA/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Mutação , Nevo de Células Epitelioides e Fusiformes/patologia , Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/genética , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
To shed more light on the pathogenesis of sebaceous carcinoma, we analysed the expression of proteins related to angiogenesis in 18 ocular and 22 extraocular sebaceous carcinomas using a broad panel of immunohistochemical markers. To quantify the expression of D2-40, vascular endothelial growth factor, vascular endothelial growth factor receptor-2 and -3, we calculated a quantification score by considering the percentage of positive tumour cells (0=0%, 1=up to 1%, 2=2-10%, 3=11-50%, and 4=>50%) in relation to the staining intensity (0=negative, 1=low, 2=medium, and 3=strong). Additionally, lymphatic microvessel density in the D2-40 stained sections was counted. Vascular endothelial growth factor receptor-3 (quantification score 9.42 ± 2.94) was significantly more strongly expressed than vascular endothelial growth factor receptor-2 (quantification score 2.15 ± 2.42, p < 0.001). Furthermore, epidermal vascular endothelial growth factor expression was negatively correlated with the intratumoural lymphatic vessel density, and the ratio of small lymphatics to large lymphatics was much higher in intratumoural tissue than in paratumoural tissue and in intraindividual control tissue, suggesting a lymphangiogenetic potential of sebaceous carcinoma.
Assuntos
Adenocarcinoma Sebáceo/patologia , Biomarcadores Tumorais/metabolismo , Neovascularização Patológica/patologia , Neoplasias das Glândulas Sebáceas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma Sebáceo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos de Coortes , Olho/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Sebáceas/fisiopatologiaRESUMO
Spiradenomas are benign cutaneous adnexal neoplasms with sweat gland differentiation that can manifest a broad spectrum of histomorphologic appearances. While they show a characteristic histopathologic phenotype and clinical management involves surgical excision with a low risk of recurrence, there have been unusual histopathologic variants of spiradenoma reported, including cases with adenoid cystic carcinoma (ACC)-like changes. Primary cutaneous ACC is a low-grade malignancy presenting as a subcutaneous mass with the potential for local invasion, perineural invasion, and high rates of local recurrence after excision. The diagnosis of spiradenomas with ACC-like features can be challenging, especially when only the ACC-like component is present for evaluation. A retrospective analysis of 21 cases of spiradenoma with ACC-like changes were obtained from large academic institutions, was performed, and summarized below. All cases showed background of conventional spiradenoma, and the ACC-like areas represented a component in all lesions. The percentage of ACC-like component ranged from 5% to 40% in all cases. The ACC-like component was multifocal and without pleomorphism, perineural and/or vascular invasion, necrosis, or increased mitotic activity. MYB translocation and protein expression was studied in 16 cases by fluorescence in situ hybridization, polymerase chain reaction, and immunohistochemistry. All studied cases were negative for MYB / NFIB , MYB L1, and MYB F by fluorescence in situ hybridization and polymerase chain reaction and 3 cases were positive for MYB expression by immunohistochemistry. Our study expands on spiradenomas with ACC-like features that ought to be considered in the differential diagnosis of cutaneous neoplasms such as primary cutaneous ACC. Our results indicate that a thorough histopathologic inspection and strict application of well-defined histologic criteria are necessary to support the diagnosis of this unusual histopathologic variant. These tumors can be difficult to diagnose, and awareness of their histomorphologic spectrum will facilitate definitive diagnosis and avoid misdiagnosis with other conditions.
Assuntos
Acrospiroma , Carcinoma Adenoide Cístico , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Carcinoma Adenoide Cístico/patologia , Acrospiroma/cirurgia , Hibridização in Situ Fluorescente , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgia , Neoplasias das Glândulas Sudoríparas/patologiaRESUMO
Secretory carcinoma of the skin is a rare adnexal carcinoma, which is morphologically and immunohistochemically identical to secretory carcinoma of the breast and is associated with the presence of t (12;15) translocation, resulting in the ETV6-NTRK3 gene fusion. Nineteen cases of primary cutaneous secretory carcinoma have been previously published in the literature. In this study, we describe 6 new cases of secretory carcinoma of the skin. The study group consisted of 5 female patients and 1 male patient, ranging in age from 57 to 98 years (mean: 74.2, median: 74). Locations included the axilla (2), neck, eyelid, thigh, and nipple base, each one. Microscopically, all but 1 tumor were well circumscribed and nonencapsulated and exhibited characteristic abundant secretions within the microcystic and tubular spaces comprised by bland oval, round to cuboidal neoplastic cells. In addition, solid areas and focal pseudopapillae were seen, and, in 1 case, a focal mucinous component with small lakes of mucin containing small tumor nests or tubules of the neoplastic cells was present. The remaining neoplasm was mostly solid and papillary, with only few characteristic lumina containing secretions. Immunohistochemically, all cases expressed S-100 protein, mammaglobin, STAT5, GATA3, and NTRK. ETV6-NTRK3 gene fusion was detected in 5 cases, whereas, in the remaining tumor, a novel NFIX-PKN1 gene fusion was found.