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1.
Ann Surg Oncol ; 31(12): 8240-8244, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39138770

RESUMO

BACKGROUND: Four externally validated sentinel node biopsy (SNB) prediction nomograms exist for malignant melanoma that each incorporate different clinical and histopathologic variables, which can result in substantially different risk estimations for the same patient. We demonstrate this variability by using hypothetical melanoma cases. METHODS: We compared the MSKCC and MIA calculators. Using a random number generator, 300 hypothetical thin melanoma "patients" were created with varying age, tumor thickness, Clark level, location on the body, ulceration, melanoma subtype, mitosis, and lymphovascular invasion (LVI). The chi-square test was used to detect statistically significant differences in risk estimations between nomograms. Multivariate linear regression was used to determine the most relevant contributing pathologic features in cases where the predictions diverged by > 10%. RESULTS: Of 300 randomly generated cases, 164 were deleted as their clinical scenarios were unlikely. The MSKCC nomogram generally calculated a lower risk than the MIA (p < 0.001). The highest risk score attained for any "patient" using MSKCC calculator was 15% achieved in one of 136 patients (0.7%), whereas using the MIA nomogram, 58 of 136 patients (43%, p < 0.001) had predicted risk >15%. Regression analysis on patients with >10% difference between nomograms revealed LVI (26, p < 0.001), mitosis (14, p < 0.001), and melanoma subtype (8, p < 0.001) were the factors with high coefficients within MIA that were not present in MSKCC. CONCLUSIONS: Nomograms are useful tools when predicting SNB risk but provide risk outputs that are quite sensitive to included predictors.


Assuntos
Melanoma , Nomogramas , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Humanos , Melanoma/patologia , Melanoma/cirurgia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Feminino , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Invasividade Neoplásica , Adulto
2.
Histopathology ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39268598

RESUMO

AIMS: BRCA1-associaed protein-1 (BAP1) inactivated tumours (BIMT) are rare melanocytic tumours that may be mistaken for Spitz tumours or melanoma. They occur sporadically or in association with the BAP1 tumour predisposition syndrome (BAP1-TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. The aim of this study was to characterise the clinicopathological features and the immunohistochemical expression pattern of preferentially expressed antigen in melanoma (PRAME) of BIMT in a large patient cohort. METHODS AND RESULTS: Ethical approval was obtained, haematoxylin and eosin-stained slides were reviewed, PRAME immunohistochemistry was performed and clinical follow-up was obtained from patient records. Sixty-five BIMT from 38 patients (F:M = 4.4:1) were identified. BIMT were typically located on the trunk and head and neck (median size = 0.5 cm). Seven patients with BAP1-TPDS (range = 16-66 years, median = 25) had multiple BIMT (median = 5), while sporadic BIMT were solitary (median patient age = 39 years). One of seven patients with BAP1-TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive without recurrence of BIMT (median follow-up = 42 months). BIMT presented as intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity and moderate to severe cytological atypia in 63% of cases. A background conventional naevus was present in 64%. PRAME immunohistochemistry showed negative or weakly patchy positive staining in all BIMT. CONCLUSIONS: BIMT are more common in a sporadic setting and behave indolently, despite worrying cytological atypia. PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma.

3.
Histopathology ; 84(6): 1047-1055, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38305122

RESUMO

AIMS: Plaque-type blue naevi are rare melanocytic tumours presenting as large, pigmented plaques at birth or during childhood. There is a risk for malignant transformation, but no larger comprehensive studies exist and the diagnosis is challenging, especially on limited biopsy material. The aim is to describe the clinicopathological features and behaviour of the disease more comprehensively. METHODS AND RESULTS: We retrieved eight plaque-type blue naevi, presenting as large, pigmented plaques (median = 7 cm; range = 3-26) most frequently affecting the scalp (four) followed by the cheek, arm, abdominal wall and gluteal cleft (one each), with a slight female predilection. Median age at time of biopsy was 39.5 years (range = 15-90), but three tumours had been present at birth and one since childhood. Histopathologically, the tumours were poorly circumscribed and composed of cellular fascicles of uniform spindle cells in a background of variably prominent pigmented dendritic cells affecting dermis and subcutaneous tissues. The majority had mutations in GNAQ. One tumour showed malignant transformation, characterised by an expansile nodule of pleomorphic epithelioid melanocytes with rhabdoid morphology, high mitotic activity and areas of necrosis. This patient developed metastatic melanoma to lymph nodes. All patients are alive with a median follow-up of 60 months. CONCLUSION: Plaque-type blue naevi are diagnostically challenging tumours with risk for malignant transformation. Awareness and familiarity with the salient clinicopathological features are necessary for reliable diagnosis, and long-term clinical follow-up is required to monitor for malignant transformation.


Assuntos
Melanoma , Nevo Azul , Nevo Pigmentado , Neoplasias Cutâneas , Recém-Nascido , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Nevo Azul/diagnóstico , Nevo Azul/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Nevo Pigmentado/patologia , Melanoma/patologia , Melanócitos/patologia
4.
Histopathology ; 85(1): 155-170, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38606989

RESUMO

The histopathological classification of melanocytic tumours with spitzoid features remains a challenging task. We confront the complexities involved in the histological classification of these tumours by proposing machine learning (ML) algorithms that objectively categorise the most relevant features in order of importance. The data set comprises 122 tumours (39 benign, 44 atypical and 39 malignant) from four different countries. BRAF and NRAS mutation status was evaluated in 51. Analysis of variance score was performed to rank 22 clinicopathological variables. The Gaussian naive Bayes algorithm achieved in distinguishing Spitz naevus from malignant spitzoid tumours with an accuracy of 0.95 and kappa score of 0.87, utilising the 12 most important variables. For benign versus non-benign Spitz tumours, the test reached a kappa score of 0.88 using the 13 highest-scored features. Furthermore, for the atypical Spitz tumours (AST) versus Spitz melanoma comparison, the logistic regression algorithm achieved a kappa value of 0.66 and an accuracy rate of 0.85. When the three categories were compared most AST were classified as melanoma, because of the similarities on histological features between the two groups. Our results show promise in supporting the histological classification of these tumours in clinical practice, and provide valuable insight into the use of ML to improve the accuracy and objectivity of this process while minimising interobserver variability. These proposed algorithms represent a potential solution to the lack of a clear threshold for the Spitz/spitzoid tumour classification, and its high accuracy supports its usefulness as a helpful tool to improve diagnostic decision-making.


Assuntos
Aprendizado de Máquina , Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Humanos , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Masculino , Feminino , Melanoma/patologia , Melanoma/diagnóstico , Melanoma/genética , Adulto , Adolescente , Adulto Jovem , Criança , Pessoa de Meia-Idade , Pré-Escolar , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/genética , Lactente , Mutação , Idoso
5.
Br J Dermatol ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392932

RESUMO

BACKGROUND: Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue neoplasm, showing smooth muscle differentiation, that arises from the mesenchymal cells of the dermis. To-date, genetic investigation of these tumours has involved studies with small sample sizes and limited analyses that identified recurrent somatic mutations in RB1 and TP53, copy number gain of MYCOD and IGF1R, and copy number loss of PTEN. OBJECTIVES: To better understand the molecular pathogenesis of cLMS, we comprehensively explored the mutational landscape of these rare tumours to identify candidate driver events. METHODS: In this retrospective, multi-institutional study, we performed whole-exome sequencing and RNA sequencing on 38 cases of cLMS. RESULTS: TP53 and RB1 were identified as significantly mutated, thus, represent validated driver genes of cLMS. COSMIC mutational signatures SBS7a/b and DBS1 were recurrent, thus, ultraviolet light exposure may be an aetiological factor driving cLMS. Analysis of significantly recurrent somatic copy number alterations, which represent candidate driver events, found focal (<10Mb) deletions encompassing TP53 and KDM6B, and amplifications encompassing ZMYM2, MYOCD, MAP2K4 and NCOR1. A larger (24 Mb) recurrent deletion encompassing CYLD was also identified as significant. Significantly recurrent broad copy number alterations, involving at least half of a chromosome arm, included deletions of 6p/q, 10p/q, 11q, 12q, 13q and 16p/q, and amplification of 15q. Notably PTEN is located on 10q, RB1 on 13q and IGFR1 on 15q. Fusion gene analysis identified recurrent CRTC1/3::MAML2 fusions, as well as many novel fusions in individual samples. CONCLUSIONS: Our analysis of the largest number of cLMS cases to-date highlights the importance of large cohort sizes and the exploration beyond small targeted gene panels when performing molecular analyses, as it allowed a comprehensive exploration of the mutational landscape of these tumours and identification of novel candidate driver events. It also uniquely afforded the opportunity to compare the molecular phenotype of cLMS with LMS of other tissue types, such as uterine and soft tissue LMS. Given that molecular profiling has resulted in the development of novel targeted treatment approaches for uterine and soft tissue LMS, our study now allows the same opportunities to become available for patients with cLMS.

6.
J Cutan Pathol ; 51(6): 424-429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38481096

RESUMO

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.


Assuntos
Proteínas Nucleares , Proteínas de Fusão Oncogênica , Neoplasias Cutâneas , Fatores de Transcrição , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Carcinoma/genética , Carcinoma/patologia , Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas que Contêm Bromodomínio
7.
Histopathology ; 82(2): 276-284, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36178027

RESUMO

Primary cutaneous apocrine carcinoma (PCAC) is a rare cutaneous malignancy that is derived from apocrine glands. Histologically, these tumours can appear well-differentiated where diagnosis should be relatively straightforward. However, occasionally these tumours can exhibit high-grade features, and in such instances the diagnosis can be challenging. A retrospective analysis of 12 cases of poorly differentiated PCAC, obtained from large academic institutions, was performed, and summarised below. Immunohistochemical studies were performed in all cases with antibodies against CK7, p63, CAM 5.2, GCDFP-15, GATA3, CEA, PR, ER, HER2, calponin, SMA, androgen receptor and EMA. All 12 cases were poorly differentiated; however, there were some histopathological clues to the diagnosis of apocrine carcinoma; namely, the presence of focal glandular formation, acrosyringial involvement and the presence of single 'pagetoid' cells within epidermis. All tumours were consistently positive for CK7, GATA3 and GCDFP-15 and negative for p63. The tumours had variable expression of CAM5.2, CEA, ER, PR, HER2, androgen receptor and EMA. In three cases, there was a preservation of the myoepithelial cell layer (with calponin and SMA), which also confirmed the primary cutaneous origin. PCAC is a difficult neoplasm to diagnose, as it can appear identical to metastatic carcinomas. We describe 12 cases of poorly differentiated PCAC, highlighting their salient clinical, histopathological and immunohistochemical features, and discuss the potential diagnostic pitfalls in distinguishing this entity from other malignant neoplasms. Our results indicate that a combination of thorough histological inspection coupled with an adequate battery of immunohistochemical stains is necessary to support the diagnosis of PCAC.


Assuntos
Carcinoma , Receptores Androgênicos , Humanos , Estudos Retrospectivos
8.
J Cutan Pathol ; 50(7): 642-646, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36617528

RESUMO

Malignant tumors arising from benign eccrine spiradenomas are rare. They are divided by morphology into low-grade and high-grade spiradenocarcinomas, with prognosis and metastatic potential closely linked to their histopathologic features. Tumors with low-grade morphology are known for their indolent behavior, with only two reported instances of metastatic spread. We report herein two further low-grade metastatic spiradenocarcinomas resulting in distant metastasis. Both tumors showed a background of a benign spiradenoma and subtle histopathologic signs of malignant transformation, characterized by loss of the dual-cell population, up to moderate cytological atypia and increased mitotic activity. Both patients developed metastases to the lungs years after the initial presentation, and one showed additional lymph nodal disease. We show that even the morphologically low-grade tumors may rarely show more aggressive behavior. Although often challenging, recognition of the morphologically low-grade malignant spiradenocarcinoma and long-term follow-up of the patients are important to detect metastatic disease.


Assuntos
Acrospiroma , Neoplasias Ósseas , Neoplasias da Mama , Carcinoma de Apêndice Cutâneo , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Humanos , Feminino , Neoplasias das Glândulas Sudoríparas/patologia , Prognóstico , Neoplasias Cutâneas/patologia
9.
Mod Pathol ; 35(10): 1405-1410, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538210

RESUMO

Digital papillary adenocarcinoma (DPAC) is a rare tumor of sweat gland origin that preferentially affects the digits and has the potential to metastasize. Its tumor diagnosis can be difficult. Well-differentiated variants of DPAC can be confused with a benign sweat gland tumor, in particular nodular hidradenoma. With the recent detection of HPV42 DNA in DPAC by next-generation sequence analysis, we reasoned that this association could be used for diagnostic purposes. To this end, we performed in situ hybridization for HPV42 on 10 tumors diagnosed as DPAC as well as 30 sweat gland tumors of various histology types, including 8 acral hidradenomas. All DPAC were positive for HPV42. Positive hybridization signals for HPV42 were seen in both primary and metastatic DPACs. All other tumors and normal tissues were negative. This study confirms the association of HPV42 with the tumor cells of DPAC through in situ hybridization. The positive test result in all lesions of DPAC and lack of detection of HPV42 in any of the acral hidradenomas or other sweat gland tumors examined in this series is encouraging for the potential diagnostic utility of the assay. As documented by two scrotal tumors of DPAC, the in situ hybridization test for HPV42 can also help support the rare occurrence of this tumor at a non-acral site.


Assuntos
Acrospiroma , Adenocarcinoma de Células Claras , Adenocarcinoma Papilar , Adenoma de Glândula Sudorípara , Neoplasias Ósseas , Neoplasias da Mama , Neoplasias de Tecido Conjuntivo , Neoplasias das Glândulas Sudoríparas , Acrospiroma/diagnóstico , Acrospiroma/genética , Acrospiroma/patologia , Adenocarcinoma Papilar/patologia , Adenoma de Glândula Sudorípara/diagnóstico , Adenoma de Glândula Sudorípara/patologia , Feminino , Humanos , Hibridização In Situ , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia
10.
Histopathology ; 80(1): 135-149, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34958502

RESUMO

Primary cutaneous and mucosal melanoma shows a wide histological spectrum. The correct diagnosis depends upon the demonstration of melanocytic differentiation by recognition of an associated in-situ component or immunohistochemical evidence of a melanocytic phenotype using conventional melanocytic markers, such as S-100, SOX10, Melan-A and HMB-45. Exceptionally, melanomas lose their melanocytic phenotype, at least focally, and show differentiation towards other lineages. Review of the literature shows that de- and trans-differentiation in melanoma is rare but probably under-recognised and under-reported. These often large and frequently ulcerated tumours affect adults and show a wide anatomical distribution, including mucosal sites, although there is a predilection for sun-damaged skin of the head and neck. Histologically, the tumours are biphasic and contain a pre-existing conventional melanoma. The de-differentiated component closely resembles atypical fibroxanthoma, both morphologically and immunohistochemically. Trans-differentiated melanoma may show rhabdomyosarcomatous or spindle cell carcinomatous features. Undifferentiated melanomas are similar tumours in which the conventional melanoma component is absent. Their diagnosis depends entirely upon the clinical context and identification of a classical melanoma driver gene mutation, i.e. BRAF V600E. The diagnosis of these rare and unusual tumours is challenging, and requires thorough tumour sampling and recognition of the background of a pre-existing but often focal conventional melanoma together with molecular analysis.


Assuntos
Desdiferenciação Celular/fisiologia , Diferenciação Celular/fisiologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Mutação , Pele/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
11.
Am J Dermatopathol ; 44(10): 774-777, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122337

RESUMO

ABSTRACT: Necrotizing infundibular crystalline folliculitis (NICF) is a rare distinct entity that was introduced in 1999. It typically presents with numerous eruptive waxy papules on the forehead and/or the upper back in adults in their fifth to seventh decade of life. The pathogenesis is unknown to date, but yeast and bacterial infection of the follicular ostia seems to contribute to the development. More recently, NICF has occasionally been observed as a side effect of targeted antitumoral therapy. Histopathologically, NICF is characterized by dilated follicular ostia filled with pale filamentous and birefringent material enclosed by parakeratotic columns of the epidermis and accompanied by a mild superficial inflammatory infiltrate of the dermis. This case report is about a 58-year-old male patient presenting with multiple eruptive keratotic papules on his forehead. Histopathology revealed all classic features of NICF. The case represents a classic example of NICF and is compared with previously published cases that are comprehensively summarized in this article.


Assuntos
Exantema , Foliculite , Adulto , Dorso/patologia , Foliculite/tratamento farmacológico , Foliculite/patologia , Humanos , Masculino , Pessoa de Meia-Idade
12.
Am J Dermatopathol ; 44(11): 843-845, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36066118

RESUMO

ABSTRACT: Digital papillary adenocarcinoma is a malignant adnexal tumor with a predilection for acral sites. Hidradenoma is a benign solid and cystic sweat gland neoplasm with focal ductal and glandular differentiation and good outcomes. Hidradenomas can occur at acral sites and show papillary structures; for this reason, they are included in the differential diagnosis of digital papillary adenocarcinoma, and immunohistochemistry is a valuable tool in this scenario. We described a case of a 43-year-old man with an epithelial tumor showing papillary structures in the intermediate phalanx of the fourth finger. There was diffuse positivity for p63 and negativity for S100 protein, suggesting that this tumor was an acral hidradenoma with papillary structures.


Assuntos
Acrospiroma , Adenocarcinoma de Células Claras , Adenocarcinoma Papilar , Adenoma de Glândula Sudorípara , Neoplasias Ósseas , Neoplasias da Mama , Carcinoma de Apêndice Cutâneo , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Acrospiroma/diagnóstico , Acrospiroma/cirurgia , Adenocarcinoma Papilar/química , Adenocarcinoma Papilar/diagnóstico , Adenocarcinoma Papilar/cirurgia , Adenoma de Glândula Sudorípara/patologia , Adulto , Humanos , Imuno-Histoquímica , Masculino , Proteínas S100 , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/metabolismo , Neoplasias das Glândulas Sudoríparas/cirurgia
13.
Mod Pathol ; 34(11): 2009-2019, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34155350

RESUMO

Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42-86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4-80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8-36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.


Assuntos
Genômica , Melanoma/patologia , Neurofibromina 1/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , DNA de Neoplasias/genética , Diagnóstico Diferencial , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Melanoma/genética , Melanoma/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
14.
Histopathology ; 78(7): 970-975, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33393120

RESUMO

AIMS: Trichoblastic carcinomas (malignant trichoblastomas) are rare and poorly documented neoplasms characterised by malignant transformation of a pre-existing benign trichoblastoma, and are subdivided histologically into low-grade and high-grade tumours. Whereas morphologically low-grade trichoblastic carcinomas show indolent behaviour, morphologically high-grade trichoblastic carcinomas have been associated with a poor prognosis, but little is known about their true biological potential. The aim of this study was to better define the clinicopathological features and outcomes of morphologically high-grade trichoblastic carcinomas. METHODS AND RESULTS: Four high-grade trichoblastic carcinomas were retrieved from departmental files, and the clinical and histopathological features and follow-up were recorded. The tumours presented as nodules on the scalps, necks and shoulders of adults (median age, 40 years; range, 30-55 years) with a female predominance of 3:1. Three patients had a longstanding history with recent change. Histologically, three tumours were characterised by an expansile cellular nodule composed of sheets of pleomorphic epithelioid cells with brisk mitotic activity and necrosis arising in a background of a benign trichoblastoma. One tumour showed a more gradual transition from a benign trichoepithelioma to an undifferentiated carcinoma with infiltrative growth and perineural infiltration. All patients were alive with no evidence of recurrence or metastasis following complete excision after a median follow-up of 96 months (range, 30-180 months). CONCLUSIONS: The correct diagnosis of high-grade trichoblastic carcinoma relies on adequate sampling and recognition of the benign trichoblastic precursor lesion, i.e. trichoblastoma or trichoepithelioma. Despite the concerning histological features of the malignant component, the tumours appear to be less aggressive than previously thought.


Assuntos
Carcinoma Basocelular , Folículo Piloso/patologia , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia
15.
J Pathol ; 252(1): 4-21, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32652526

RESUMO

In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye, and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways, and tumour-microenvironmental interactions is needed. This is where animal models are of critical importance. The mouse is the foremost used model of human melanoma. Arguably this is due to its plethora of benefits as a laboratory animal; however, it is important to note that unlike humans, melanocytes are not present at the dermal-epidermal junction in mice and mice do not develop melanoma without genetic manipulation. In contrast, there are numerous reports of animals that spontaneously develop melanoma, ranging from sharks and parrots to hippos and monkeys. In addition, several domesticated and laboratory-bred animals spontaneously develop melanoma or UV-induced melanoma, specifically, fish, opossums, pigs, horses, cats, and dogs. In this review, we look at spontaneously occurring animal 'models' of melanoma and discuss their relevance to the different types of melanoma found in humans. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland..


Assuntos
Doenças do Gato/patologia , Doenças do Cão/patologia , Doenças dos Peixes/patologia , Doenças dos Cavalos/patologia , Melanoma/veterinária , Neoplasias Cutâneas/veterinária , Doenças dos Suínos/patologia , Animais , Doenças do Gato/genética , Gatos , Doenças do Cão/genética , Cães , Doenças dos Peixes/genética , Doenças dos Cavalos/genética , Cavalos , Humanos , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Suínos , Doenças dos Suínos/genética
16.
J Cutan Pathol ; 48(7): 847-855, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33340147

RESUMO

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.


Assuntos
Imunofenotipagem/métodos , Mioepitelioma/diagnóstico , Mioepitelioma/metabolismo , Neoplasias Cutâneas/patologia , Actinas/metabolismo , Adenoma Pleomorfo/patologia , Adulto , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Conscientização , Biomarcadores/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma/patologia , Antiportadores de Cloreto-Bicarbonato/metabolismo , Desmina/metabolismo , Diagnóstico Diferencial , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica/métodos , Queratinas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Mucina-1/metabolismo , Mioepitelioma/patologia , Mioepitelioma/ultraestrutura , Proteínas S100/metabolismo , Calponinas
17.
Mod Pathol ; 33(Suppl 1): 25-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31558783

RESUMO

The group of malignant sweat gland neoplasms is characterized by a wide biologic spectrum, including tumors with indolent behavior, low-grade malignant potential with locally destructive tumor growth and high local recurrence rates and high-grade malignant potential characterized by risk for disseminated disease and disease-related mortality. Reliable diagnosis to predict behavior may be challenging for a number of reasons. The clinical presentation is often nonspecific. Many of the tumors are rare, and they are only infrequently encountered in routine diagnostic practice. A significant subset of tumors shows bland and innocuous histologic features. They are easily mistaken for benign tumors despite their potential for destructive growth and aggressive disease course. At the other end of the spectrum the tumors may resemble poorly differentiated carcinoma or adenocarcinoma and recognition relies entirely on sampling and carful histological examination. The tumors may be inseparable from cutaneous metastases from visceral primaries by morphology and immunohistochemistry, requiring careful clinical correlation and work-up. Conversely, cutaneous metastases are readily mistaken for cutaneous primary tumors. While the presence of a myoepithelial layer is a helpful feature in excluding metastatic deposits, it does not imply benign behavior of sweat gland tumors in general. The above issues and challenges are exemplified in the discussion of selected sweat gland carcinoma in this manuscript, with a focus on recently described entities and those with novel findings.


Assuntos
Erros de Diagnóstico/prevenção & controle , Neoplasias das Glândulas Sudoríparas/patologia , Biópsia , Diagnóstico Diferencial , Humanos , Valor Preditivo dos Testes , Neoplasias das Glândulas Sudoríparas/secundário
18.
Histopathology ; 77(3): 449-452, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32359178

RESUMO

AIMS: Microcystic adnexal carcinoma is a distinctive sweat duct carcinoma of low-grade malignant potential with a risk for locally destructive growth and local recurrence. Distant metastases and disease-related mortality are exceptional. The histological hallmarks of these tumours are the diffusely infiltrative growth within the dermis, the frequent invasion of subcutaneous structures, the presence of perineurial invasion, and the bland cytological features. The tumours are organised in cords and strands, and show keratocyst formation and duct differentiation in varying proportions. Marked cytological atypia, nuclear pleomorphism, brisk and atypical mitotic activity and necrosis are not typically seen in these tumours. METHODS AND RESULTS: We report two patients presenting with large, slowly growing tumours on the face showing areas of morphologically high-grade carcinoma arising on a background of unequivocal microcystic adnexal carcinoma. Both patients are alive with follow-up of up to 6 years, with no evidence of disease. CONCLUSIONS: Morphologically high-grade transformation in microcytic adnexal carcinoma is a rare phenomenon that does not appear to confer a risk for aggressive behaviour. Recognition depends on sampling of the areas of conventional microcystic adnexal carcinoma.


Assuntos
Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos
19.
Histopathology ; 76(5): 640-649, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31821583

RESUMO

Cutaneous sebaceous neoplasms show a predilection for the head and neck area of adults and include tumours with benign behaviour, sebaceous adenoma and sebaceoma, and sebaceous carcinoma with potential for an aggressive disease course at the malignant end of the spectrum. The majority of tumours are solitary and sporadic, but a subset of tumours may be associated with Lynch syndrome, also known as hereditary non-polyposis colon cancer (HNPCC) and previously referred to as Muir-Torre syndrome (now known to be part of Lynch syndrome). This review provides an overview of the clinical and histological features of cutaneous sebaceous neoplasia with an emphasis on differentiating features and differential diagnosis. It also offers insights into the recently described molecular pathways involved in the development of sebaceous tumours and their association with Lynch syndrome.


Assuntos
Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/genética , Neoplasias das Glândulas Sebáceas/patologia , Humanos
20.
Mod Pathol ; 31(3): 418-428, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29099504

RESUMO

Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization. In an analysis of the entire coding region of 341 oncogenes and tumor suppressor genes in 13 atypical fibroxanthomas using an established hybridization-based next-generation sequencing approach, we found that these tumors harbor a large number of mutations. Gene alterations were identified in more than half of the analyzed samples in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter. The presence of these alterations was verified in 26 atypical fibroxanthoma and 35 pleomorphic dermal sarcoma samples by targeted amplicon-based next-generation sequencing. Similar mutation profiles in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter were identified in both atypical fibroxanthoma and pleomorphic dermal sarcoma. Activating RAS mutations (G12 and G13) identified in 3 pleomorphic dermal sarcoma were not found in atypical fibroxanthoma. Comprehensive DNA copy number analysis demonstrated a wide array of different copy number gains and losses, with similar profiles in atypical fibroxanthoma and pleomorphic dermal sarcoma. In summary, atypical fibroxanthoma and pleomorphic dermal sarcoma are highly mutated tumors with recurrent mutations in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter, and a range of DNA copy number alterations. These findings suggest that atypical fibroxanthomas and pleomorphic dermal sarcomas are genetically related, potentially representing two ends of a common tumor spectrum and distinguishing these entities is at present still best performed using histological criteria.


Assuntos
Caderinas/genética , Receptor Notch1/genética , Receptor Notch2/genética , Sarcoma/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Hibridização Genômica Comparativa , Inibidor p16 de Quinase Dependente de Ciclina/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Regiões Promotoras Genéticas , Telomerase/genética , Proteína Supressora de Tumor p53/genética
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