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1.
Am J Surg Pathol ; 46(1): 11-17, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334690

RESUMO

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.


Assuntos
Carcinoma/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Sarcoma/patologia , Neoplasias Testiculares/patologia , Tumor de Wilms/patologia , Adolescente , Adulto , Carcinoma/mortalidade , Carcinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/cirurgia , Tumores Neuroectodérmicos Primitivos Periféricos/mortalidade , Tumores Neuroectodérmicos Primitivos Periféricos/cirurgia , Orquiectomia , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/cirurgia , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/cirurgia , Tumor de Wilms/mortalidade , Tumor de Wilms/cirurgia , Adulto Jovem
2.
Cancers (Basel) ; 12(12)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327406

RESUMO

Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease.

3.
Ann Diagn Pathol ; 48: 151593, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32836180

RESUMO

The urinary bladder may be involved by a variety of secondary tumors that originate from other organs. Bladder secondary tumors are rare and may be mistaken as bladder primary tumors because of their overlapping morphologic features. To avoid the diagnostic pitfalls, we analyzed the clinicopathologic features of bladder secondary tumors in a large cohort of patients. Our patient cohort consisted of 45 females and 38 males with a mean age of 58.7 ± 15.4 years (range 10-87 years). The tumors involved the bladder via direct extension from adjacent organs (n = 42) and distant metastasis (n = 41). In females, the majority of secondary tumors originated from the gynecologic tract (n = 25), and other common origins included the colon/rectum (n = 5) and breast (n = 4). In males, the most common origin was the prostate (n = 18), followed by the colon/rectum (n = 4) and kidney (n = 3). 75.9% of the secondary tumors were adenocarcinoma (n = 63), and other common tumor types included sarcoma (n = 6), squamous cell carcinoma (n = 5), melanoma (n = 4), and neuroendocrine carcinoma (n = 3). 67.5% of patients (n = 56) died of the disease with a median overall survival of 23 months from the time of secondary involvement of the bladder. Patients with secondary tumors via direct extension had a median survival time of 20 months, which was not significantly different from that for patients with secondary involvement via distant metastasis (24 months) (p = 0.83). Median survival in cases with prostate primary was 20 months as compared to 23 months for all other tumor types (p = 0.68). The majority of secondary tumors are composed of adenocarcinoma, which highlights the importance of differentiating primary from secondary involvement in bladder adenocarcinoma. Regardless of the origin, bladder secondary tumors are associated with a poor prognosis.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Adenocarcinoma/diagnóstico , Adulto , Idoso , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/secundário , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/secundário , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Sarcoma/diagnóstico , Sarcoma/secundário , Análise de Sobrevida , Neoplasias da Bexiga Urinária/secundário
4.
Am J Clin Pathol ; 154(2): 208-214, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32253420

RESUMO

OBJECTIVES: Bladder cancers invading the muscularis mucosae (MM) are treated differently from those invading the muscularis propria (MP). However, it may be difficult to determine the type of smooth muscle in transurethral resection (TUR) or biopsy specimens. We aimed to investigate the clinicopathologic features of bladder cancers involving smooth muscle of indeterminate type (SMIT) in TUR specimens in comparison with those invading the MM. METHODS: We identified 103 patients with bladder cancer involving SMIT (n = 27) or the MM (n = 76) in TUR specimens. All patients underwent subsequent restaging TUR or cystectomy. RESULTS: Bladder cancer with SMIT invasion showed a significantly higher rate of MP invasion in the subsequent specimens than those invading the MM (52% vs 29%). Lack of MP in the TUR specimens had a significantly higher risk of MP invasion in the subsequent specimens than those with the MP (61% vs 40%). The overall survival time for patients with SMIT invasion was significantly shorter than those with MM invasion. CONCLUSIONS: Bladder cancers with SMIT invasion in TUR specimens show more frequent cancer upstaging in the subsequent specimens and a poorer clinical outcome than those invading the MM, which highlights the importance of a cancer restaging procedure for these patients.


Assuntos
Carcinoma de Células de Transição/patologia , Mucosa/patologia , Músculo Liso/patologia , Invasividade Neoplásica/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células de Transição/cirurgia , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/cirurgia , Músculo Liso/cirurgia , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/patologia , Urotélio/cirurgia
5.
Am J Pathol ; 189(6): 1180-1189, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31079810

RESUMO

Easily accessible biomarkers that may inform on the metastatic potential of localized prostate cancer are urgently needed. Herein, we show that syntaphilin (SNPH), a molecule originally identified as a negative regulator of mitochondrial dynamics in neurons, is abundantly expressed in prostate cancer. SNPH distribution in prostate cancer is spatially biphasic, with high expression at the invasive front, correlating with increased proliferative rates, as determined by Ki-67 labeling, and reduced levels in the central tumor bulk, which are further decreased in patients with distant metastases. Higher levels of SNPH are observed with increasing Gleason grade. Prostate tumors predominantly express a novel, extraneuronal isoform of SNPH that accumulates in mitochondria and maintains oxidative metabolism and tumor cell proliferation. These data suggest that SNPH is a novel marker of high Gleason grade prostate cancer, differentially expressed at the invasive front compared with the central tumor bulk, and is potentially down-regulated in metastatic disease. This biphasic pattern of expression may reflect a dual function of SNPH in controlling the balance between cell proliferation and invasion in tumors.


Assuntos
Biomarcadores Tumorais/biossíntese , Regulação da Expressão Gênica , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Neoplasias da Próstata/patologia , Isoformas de Proteínas/biossíntese
6.
Med Mol Morphol ; 47(1): 57-61, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23955668

RESUMO

Mammary analogue secretory carcinoma (MASC) is a recently described malignancy of the salivary glands characterized by an ETV6-NTRK3 (EN) fusion gene. Morphologically, MASC is sometimes difficult to distinguish from acinic cell carcinoma. Consequently, identifying the chromosomal translocation is essential for diagnosis. We present a case of parotid gland MASC in a 13-year-old boy. To the best of our knowledge, this is the youngest case reported in the literature. Histologic evaluation showed a tumor composed of microcysts, tubular structures, solid nests, or papillary architecture, with secretions within the lumens of the cysts or tubules. Immunohistochemically, tumor cells showed diffuse positive staining of S-100 protein, cytokeratin 19, and vimentin. ETV6 rearrangement was detected by fluorescence in situ hybridization and EN fusion transcripts were verified by reverse transcription (RT-PCR) assay.


Assuntos
Glândula Parótida/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Adolescente , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/metabolismo , Diagnóstico Diferencial , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Queratina-19/metabolismo , Masculino , Proteínas de Fusão Oncogênica/genética , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas S100/metabolismo , Neoplasias das Glândulas Salivares/diagnóstico , Taiwan , Vimentina/metabolismo , Variante 6 da Proteína do Fator de Translocação ETS
7.
Med Mol Morphol ; 46(2): 109-13, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23460079

RESUMO

Primitive myxoid mesenchymal tumor of infancy is an extremely rare and recently recognized soft tissue tumor entity with a tendency for multiple recurrences. Only ten cases have been described in the literature and most cases are reported in Western countries. This tumor ranges in size from 2 to 15 cm and is characterized microscopically by a diffuse growth of primitive cells in a myxoid background with focal fascicles or a herringbone pattern. In this study, we describe a primitive myxoid mesenchymal tumor of infancy on the scalp of a 3-month-old Taiwanese boy. The histology showed typical morphology and the tumor cells showed vimentin and CD99 immunoreactivities. The translocation t(12,15)(p13;q25) was not found by fluorescence in situ hybridization. After complete surgical excision, no recurrence was noted during an 18-month follow-up.


Assuntos
Couro Cabeludo/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Antígeno 12E7 , Antígenos CD/metabolismo , Moléculas de Adesão Celular/metabolismo , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias de Tecidos Moles/terapia , Vimentina/metabolismo
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