RESUMO
Metaplastic breast carcinoma (MBC) and gynecologic carcinosarcoma (GCS) are rare, clinically aggressive cancers that demonstrate epithelial components and mesenchymal or sarcomatoid components. In this study, we assessed PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in MBC and GCS. Overall, PD-L1 positivity using the SP142 clone was seen in 50 % of MBC and 51.9 % of GCS cases, with PD-L1 expression in tumor cells significantly higher in MBC cases (p = 0.034), and PD-L1 expression in immune cells similar in MBC and GCS cases. PD-L1 expression was significantly higher in epithelial components than in mesenchymal components in both MBC and GCS cases (p = 0.0005). TILs were low in the majority of MBC and GCS cases (≥ 10 %) and generally correlated with PD-L1 expression; however, many PD-L1 positive cases with low TILs were seen. PD-L1 expression using the 22C3 clone was additionally assessed, with positivity seen in 62.9 % of MBC cases and 30 % of GCS cases. Concordance between SP142 and 22C3 results was seen in 62.5 % of MBC cases and 80 % of GCS cases. Overall, our findings suggest that a subset of MBC and GCS cases may benefit from immune checkpoint inhibitor therapy. Our findings also illustrate unique aspects of PD-L1 expression patterns in these tumors which may harbor additional prognostic and therapeutic significance.
RESUMO
We report a collision tumor in the ovary of a 60-yr-old woman composed of high-grade serous carcinoma and Sertoli-Leydig cell tumor. Collision tumors in the ovary are rare and to the best of our knowledge, combination of ovarian high-grade serous carcinoma and Sertoli-Leydig cell tumor has not been described before.
Assuntos
Carcinoma , Neoplasias Ovarianas , Tumor de Células de Sertoli-Leydig , Masculino , Feminino , Humanos , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/patologia , Neoplasias Ovarianas/patologiaRESUMO
Seromucinous carcinoma of the ovary was a newly defined category in the revised 2014 World Health Organization Classification of Tumors of Female Reproductive Organs. It was defined as a carcinoma composed of predominantly of serous and endocervical-type mucinous epithelium. Foci containing clear cells, and areas of endometrioid and squamous differentiation are not uncommon. It is a rare entity with morphologic and immunophenotypic features overlapping other types of ovarian carcinoma. There are different opinions as to whether it is a distinct entity or a histologic variant of well-established entities. Subsequent, to the writing of this manuscript the WHO 2020 reclassified this tumor as a type of endometrioid carcinoma. Here we present a case of seromucinous carcinoma of bilateral ovaries that had variable differentiation and morphology at different sites. Tumor in the fallopian tubes, ovarian surfaces, omentum, and peritoneal surfaces displayed predominant features of low-grade serous carcinoma, while the tumor in the ovaries had predominant mucinous carcinoma morphology with a confluent/expansile growth pattern. The mucosal involvement of the fallopian tubes morphologically mimicked serous tubal intraepithelial carcinoma.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Neoplasias das Tubas Uterinas/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Carcinoma in Situ/patologia , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias das Tubas Uterinas/secundário , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Salpingo-Ooforectomia , Tomografia Computadorizada por Raios XAssuntos
Recidiva Local de Neoplasia , Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Pessoa de Meia-Idade , Gradação de TumoresRESUMO
PURPOSE: To use simulated arthroscopic knot tying to assess (1) whether epithelial cells from the surgeon's hands were transmitted to the suture and (2) whether the number of knots tied or the presence of glove tears would correlate with the number of cells transmitted. METHODS: Knots were tied in a simulated arthroscopic environment using a nonabsorbable No. 2 suture over a metal hook. The surgeon was double gloved for each knot tied. For each "anchor," a surgeon's knot was tied, followed by 3 reversed half-hitches on alternating posts. Multiple skin lacerations were sustained by the surgeon during each knot-tying session. Gloves were collected after tying 2, 4, or 6 anchors. Gloves were tested for perforation by (1) electroconductivity and (2) saline solution load testing. Cytopathologic ThinPrep analysis was applied and allowed for the number of epithelial cells found on each suture (within 10 high-powered fields) to be counted. Statistical analysis included analysis of variance and logistic regression. RESULTS: There was no significant difference in the number of epithelial cells identified in any of the groups compared with the negative control groups (P > .05) or with each other (P > .05). Glove tears were present in 3.3% of gloves (50% in inner and 50% in outer gloves) and 1.7% of gloves (50% in inner and 50% in outer gloves) by electroconductivity and saline solution load testing, respectively. There was no significant association between glove tears and the number of epithelial cells found on the suture (P > .05). CONCLUSIONS: Epithelial cells were transmitted to the suture during simulated arthroscopic knot tying. However, despite multiple skin lacerations produced during knot-tying sessions, the number of cells transmitted was not significantly different when compared with the negative controls. The number of cells transmitted did not correlate with the number of knots tied and/or the presence of glove tears. CLINICAL RELEVANCE: Skin lacerations on the surgeon's fingers are often noted after arthroscopic knot tying. However, despite these skin lacerations, no skin tissue is transferred across the surgical gloves to the suture itself.
Assuntos
Artroscopia , Células Epiteliais/citologia , Luvas Cirúrgicas , Pele/lesões , Suturas , Contagem de Células , Falha de Equipamento , Humanos , Lacerações , CirurgiõesRESUMO
BACKGROUND: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. METHODS: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. RESULTS: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. CONCLUSIONS: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).
Assuntos
Interleucina-6/antagonistas & inibidores , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Ovarianas/complicações , Síndromes Paraneoplásicas , Trombocitose/etiologia , Animais , Anticorpos Monoclonais/uso terapêutico , Plaquetas/imunologia , Modelos Animais de Doenças , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Estimativa de Kaplan-Meier , Camundongos , Camundongos Knockout , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Contagem de Plaquetas , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/deficiência , Transdução de Sinais , Trombopoetina/antagonistas & inibidores , Trombopoetina/sangueRESUMO
AIMS: We have demonstrated previously that gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are of limited utility in triple-negative breast cancer (TNBC). GATA-binding protein 3 (GATA-3) is an emerging breast-associated immunohistochemical (IHC) marker with limited data in TNBC. Here, we examined GATA-3 expression in TNBC in comparison with GCDFP-15 and MAM. METHODS AND RESULTS: We studied GATA-3, GCDFP-15 and MAM IHC expression in 62 primary and 68 metastatic TNBCs. In primary TNBCs, GATA-3 staining was observed in 25 cases (40%), including 16 cases that were negative for GCDFP-15 and MAM. In metastatic TNBCs, GATA-3 staining was observed in 30 cases (44%), including 16 cases that were negative for GCDFP-15 and MAM. The expression frequency of any of the markers was 56% in primary and 62% in metastatic TNBCs. However, when focal staining was excluded, the expression frequency of any marker dropped to 31% and 44%, respectively. CONCLUSION: GATA-3 is expressed at a higher frequency by IHC in TNBC compared to GCDFP-15 and MAM, although the tissue specificity of the latter markers may be superior. When evaluating a triple-negative tumour, including GATA-3 in a panel of markers may increase the diagnostic accuracy for tissue origin in the appropriate clinical setting.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Fator de Transcrição GATA3/metabolismo , Glicoproteínas/metabolismo , Mamoglobina A/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Técnicas Imunoenzimáticas/métodos , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Coloração e Rotulagem , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp.
Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Peritoneais/patologia , Pólipos/patologia , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Gradação de Tumores , Neoplasias Ovarianas/patologiaRESUMO
A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.
Assuntos
Carcinoma Intraductal não Infiltrante/patologia , Carcinoma de Células Escamosas/patologia , Glândulas Exócrinas/patologia , Vulva/patologia , Neoplasias Vulvares/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Carcinossarcoma/patologia , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Glândulas Mamárias Humanas , Metástase Neoplásica/radioterapia , Recidiva Local de Neoplasia/cirurgia , Doença de Paget Extramamária/patologia , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/cirurgiaRESUMO
We present the case of a 33-year-old female who developed a cystic nodule on the vulva during pregnancy. Immediately following Cesarean section, the lesion was biopsied and histologic examination revealed a dermal tumor composed of glandular structures arranged in a labyrinth pattern. The glandular structures displayed cytoplasmic vacuolization, large atypical nuclei, prominent nucleoli and scattered eosinophilic luminal secretions. Immunohistochemistry showed the tumor cells to be diffusely positive for CK7 and progesterone receptor with focal expression of mammaglobin and GCDFP-15. The tumor cells were negative for estrogen receptor and CK20. These histologic and immunophenotypic findings were consistent with hidradenoma papilliferum. Our unusual (and to our knowledge first reported) case demonstrates hidradenoma papilliferum in association with pregnancy and raises the possibility of cytologic atypia and lactational change being secondary to hormonal changes in pregnancy.
RESUMO
Epithelioid sarcoma is a rare, aggressive keratin-positive sarcoma that co-expresses CD34 in 50% of cases and may mimic an angiosarcoma. Recently, we have observed one case of epithelioid sarcoma that labeled for ERG, an ETS family regulatory transcription factor, which is considered to be a reliable marker for vascular differentiation. We investigated the prevalence of nuclear expression of ERG and FLI1, a homologous transcription factor, in these tumors. A formalin-fixed paraffin-embedded tissue microarray of 37 epithelioid sarcomas was examined. Immunohistochemistry was performed using anti-ERG monoclonal antibody to the N-terminus, anti-ERG monoclonal antibody to the C-terminus and anti-FLI1 monoclonal antibody. Comparison was made with CD34, CD31, and D2-40 labeling. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0: no staining; 1+: <5%; 2+: 5-25%; 3+: 26-50%; 4+: 51-75%; and 5+: 76-100%), and the intensity of staining was graded as weak, moderate, or strong. Nuclear staining for the N-terminus of ERG was seen in 19 out of 28 cases: 10 with diffuse(4 to 5+) strong/moderate labeling; 1 with 2+ moderate labeling and 8 with weak labeling (1 to 4+, 2 each). Focal staining for the C-terminus of ERG was seen in only 1 out of 29 cases (2+ moderate). FLI1 labeling was seen in nearly all (28 out of 30) cases: 16 with diffuse (5+) predominantly moderate labeling, and 8 cases with diffuse(5+) weak labeling. The remainder had variable moderate (1 to 3+) or weak (1 to 4+) FLI1 staining. CD34 was positive in 22 out of 30 cases and D2-40 was found to be positive in 22 out of 31 cases. All cases were negative for CD31 (0 out of 30). Epithelioid sarcoma can label with antibodies to the N-terminus of ERG, FLI1, and D2-40, which may cause diagnostic confusion for a vascular tumor. A panel of other antibodies including SMARCB1 and CD31 should be used in evaluating these tumors. ERG antibody selection is also critical, as those directed against the C-terminus are less likely to label epithelioid sarcoma.
Assuntos
Biomarcadores Tumorais/análise , Proteína Proto-Oncogênica c-fli-1/análise , Sarcoma/química , Transativadores/análise , Anticorpos Monoclonais , Anticorpos Monoclonais Murinos , Especificidade de Anticorpos , Antígenos CD34/análise , Núcleo Celular/química , Núcleo Celular/patologia , Reações Cruzadas , Humanos , Imuno-Histoquímica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Valor Preditivo dos Testes , Proteína Proto-Oncogênica c-fli-1/imunologia , Reprodutibilidade dos Testes , Sarcoma/patologia , Análise Serial de Tecidos , Transativadores/imunologia , Regulador Transcricional ERGRESUMO
BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild-type KRAS by conventional PCR-Sanger sequencing were further analysed by full COLD (co-amplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR-Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations.
Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenoma Seroso/genética , Mutação , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Benzimidazóis/farmacologia , Morte Celular/efeitos dos fármacos , Cistadenocarcinoma Seroso/patologia , Cistadenoma Seroso/patologia , Análise Mutacional de DNA/métodos , DNA de Neoplasias/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estimativa de Kaplan-Meier , MAP Quinase Quinase Quinases/antagonistas & inibidores , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Células Tumorais Cultivadas , Adulto JovemRESUMO
BACKGROUND: Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. QUESTIONS/PURPOSES: We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient- and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. METHODS: Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. RESULTS: Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. CONCLUSIONS: In this small retrospective study, it appeared that ifosfamide-based adjuvant chemotherapy combined with surgical resection offered a treatment advantage compared with patients who did not receive the drug in patients with dedifferentiated chondrosarcoma, although disease-specific survival for patients who have this rare tumor remains dismal. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Desdiferenciação Celular , Condrossarcoma/tratamento farmacológico , Ifosfamida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Condrossarcoma/mortalidade , Condrossarcoma/secundário , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteotomia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Texas , Fatores de Tempo , Resultado do TratamentoRESUMO
Spontaneous hip dislocation due to intraarticular neurofibroma in patients with neurofibromatosis type 1 is extremely rare. We describe the imaging features of spontaneous dislocation of hip due to histologically proven intraarticular neurofibroma in young woman with neurofibromatosis type 1, and review the literature.
Assuntos
Neoplasias Femorais/complicações , Neoplasias Femorais/diagnóstico , Luxação do Quadril/diagnóstico , Luxação do Quadril/etiologia , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Neoplasias Femorais/cirurgia , Luxação do Quadril/cirurgia , Humanos , Neurofibromatose 1/cirurgia , Resultado do TratamentoRESUMO
Published data on combined breast and gynecologic [breast/gyn] surgical pathology fellowship training programs are limited. Our study aimed to survey the landscape of such fellowships in the United States (US), including specific information about their characteristics and the educational activities therein. Using web searches, we identified programs offering combined breast/gyn surgical pathology fellowship training. We developed a 26-item questionnaire asking program directors to report on the characteristics of their fellowship training structure. The search revealed 25 academic based programs offering one-year combined breast/gyn fellowship training, predominantly located (40 %) in the Northeast area. The following data was obtained: 44 % of the programs were accredited by the ACGME, 82 % required >19 weeks of breast and gyn service, and 69.6 % accepted the common application, 54.5 % of programs require completion of a research project for graduation. An annual average of 3000 breast and 3000 gyn cases appears to be the usual volume of cases. Interestingly, only 36 % of the program directors are graduates of a combined breast/gyn fellowship program. In conclusion, we present the most comprehensive and up-to-date census of combined breast/gyn pathology fellowships in the US. Our study provides valuable information on the current state of combined breast/gyn pathology fellowship training. The information will be helpful to current and prospective trainees, as well as program leaders.
RESUMO
BACKGROUND: A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). METHODS: A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). RESULTS: A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. CONCLUSIONS: ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer.
Assuntos
Antígeno Ca-125/sangue , Neoplasias Ovarianas/sangue , Idoso , Algoritmos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Pós-Menopausa/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
To facilitate accurate detection of estrogen receptor (ER) expression in breast tumors, the American Society of Clinical Oncology/College of American Pathologists recommends that cold ischemia time be kept under 1 h. However, data to address the upper threshold of cold ischemia time are limited. Although it is our routine practice to keep cold ischemia time under 1 h for breast core biopsy specimens, this is difficult for surgical specimens because of the comprehensive intraoperative assessment performed at our institution. In this retrospective study, we compared ER immunohistochemical staining results in paired breast tumor core biopsy specimens and resection specimens with cold ischemia times ranging from 64 to 357 min in 97 patients. The staining category (≥10%, positive; 1-9%, low positive; <1%, negative) between the core biopsy and resection specimens changed for five patients (5%). The weighted Kappa statistic for ER staining category between the two specimen types was 0.86 (95% confidence interval, 0.74-0.99), indicating good concordance. The difference in the percentage of ER staining between core biopsy and resection was not significantly associated with cold ischemia time (P=0.81, Spearman correlation). Although we did not observe significant associations between the difference in ER staining in the two specimen types and cold ischemia time after placing the patients in three groups of 'increase', 'decrease' and 'no change' using a difference of 25% in ER staining percentage as the cutoff, a trend of decreased ER staining with cold ischemia time >2 h was detected. No statistically significant association was found between the change of ER staining and the history of neoadjuvant chemotherapy. Our findings indicate that prolonged cold ischemia time up to 4 h (97% of our cohort) in the practice setting of our institution has minimal clinical impact on ER immunohistochemical expression in breast tumors.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Isquemia Fria/métodos , Receptores de Estrogênio/análise , Manejo de Espécimes/métodos , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica/métodos , Estudos Retrospectivos , Fixação de TecidosRESUMO
AIMS: In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis. METHODS AND RESULTS: We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining. CONCLUSIONS: Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker.
Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Transporte/metabolismo , Glicoproteínas/metabolismo , Mamoglobina A/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Imuno-Histoquímica/métodos , Proteínas de Membrana Transportadoras , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The objective of this study is to investigate whether wild-type TP53 status in high-grade serous ovarian carcinoma is associated with poorer survival. METHODS: Clinical and genomic data of 316 sequenced samples from The Cancer Genome Atlas (TCGA) ovarian high-grade serous carcinoma study were downloaded from TCGA data portal. Association between wild-type TP53 and survival was analyzed with Kaplan Meier method and Cox regression. The diagnosis of high-grade serous carcinomas was evaluated by reviewing pathological reports and high-resolution hematoxylin and eosin (H&E) images from frozen sections. The authenticity of wild-type TP53 in these tumor samples was assessed by analyzing SNP array data with ASCAT algorithm, reverse phase protein array (RPPA) data and RNAseq data. RESULTS: Fifteen patients with high grade serous ovarian carcinomas were identified to have wild-type TP53, which had significantly shorter survival and higher chemoresistance than those with mutated TP53. The authenticity of wild-type TP53 status in these fifteen patients was supported by SNP array, RPPA, and RNAseq data. Except four cases with mixed histology, the classification as high grade serous carcinomas was supported by pathological reports and H&E images. Using RNAseq data, it was found that EDA2R gene, a direct target of wild-type TP53, was highly up-regulated in samples with wild-type TP53 in comparison to samples with either nonsense or missense TP53 mutations. CONCLUSION: Although patients with wild-type TP53 ovarian cancer were rare in the TCGA high grade ovarian serous carcinomas cohort, these patients appeared to have a poorer survival and were more chemoresistant than those with mutated TP53. Differentially expressed genes in these TP53 wild-type tumors may provide insight in the molecular mechanism in chemotherapy resistance.
Assuntos
Cistadenocarcinoma Seroso/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes p53/genética , Neoplasias Ovarianas/genética , Receptor Xedar/genética , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Análise Serial de Proteínas , Análise de Sequência de RNA , Regulação para CimaRESUMO
OBJECTIVE: We previously found that galectin-7 was upregulated in patients with cervical cancer who remained recurrence-free after chemoradiation. We hypothesized that pretreatment levels of galectin-7 predict radiation response in patients with squamous cell carcinoma (SCC) of the cervix. METHODS: Galectin-7 expression was assessed by immunohistochemical staining of a tissue microarray of paraffin-embedded specimens from 161 patients with cervical SCC treated with definitive radiation therapy in 1980-1999. Galectin-7 expression was scored as absent or present. Distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were computed using the Kaplan-Meier method and log-rank tests. RESULTS: The median age at diagnosis was 45 years (range 21-85) and median follow-up interval was 71 months (range 0-285). Of the 161 patients, 105 (65%) had FIGO stage IB disease, 18 (11%) stage IIA, and 38 (24%) stage IIB. Median tumor diameter was 5.5 cm (range 3.5-8). Seven patients (4%) received concurrent chemotherapy; 139 patients (86%) had galectin-7-positive tumors and 22 (14%) galectin-7-negative tumors. Five-year DMFS rates for patients with galectin-7-positive versus -negative tumors were 73% and 55% (p=0.05); DSS, 65% and 36% (p=0.004); and OS, 64% and 36% (p=0.005). In multivariate analysis adjusting for age, stage, and tumor diameter, galectin-7 expression remained a significant predictor of DMFS (hazard ratio [HR]=0.43, p=0.03), DSS (HR=0.34, p=0.001), and OS (HR=0.34, p=0.001). CONCLUSIONS: Elevated galectin-7 expression is associated with improved outcomes after radiation therapy for cervical cancer. Further studies are required to validate these findings and clarify the role of galectin-7 in disease progression and radiation response.