RESUMEN
Prostate cancer stands as the most prevalent malignant tumor among men; with its incidence increasing with advancing age. The spectrum of patient care options for this disease is broad, encompassing approaches such as "active surveillance," definitive radiation therapy, robot-assisted surgery, among others. These diverse modalities afford opportunities for cure or successful management in the majority of cases. It is paramount to underscore that optimal treatment hinges upon a multidisciplinary framework, wherein the coordinated efforts of allied healthcare professionals yield the highest standard of patient care. Hence, it is imperative for pathologists to keep abreast of contemporary processing and specimen collection protocols, as well as the potential necessity of supplementary investigations and their clinical significance. The latest Hungarian guideline on prostate cancer care features a dedicated chapter delineating the pivotal role and responsibilities of pathologists. Through this discourse, we aim to consolidate and disseminate pertinent insights, thereby fostering the continuing enhancement of pathologists' knowledge and elucidating the intricacies of histological processing to our clinical counterparts.
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Neoplasias de la Próstata , Manejo de Especímenes , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Hungría , Biopsia/normas , Biopsia/métodos , Manejo de Especímenes/normas , Manejo de Especímenes/métodos , Próstata/patología , Próstata/cirugía , Patólogos , Prostatectomía/métodos , Guías de Práctica Clínica como AsuntoRESUMEN
Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling.
RESUMEN
Renal cell carcinoma (RCC) is the most common malignant kidney tumor. It is not a single entity but an umbrella term for several distinct tumor types. The most prevalent and clinically significant subtype of RCC is clear cell carcinoma, which consists of cells with empty cytoplasm. These tumor cells harbor biallelic loss of the VHL gene, resulting in a pseudohypoxic state that promotes angiogenesis and cellular proliferation. Papillary RCC and chromophobe carcinoma are also common subtypes, with the former displaying a papillary appearance and cMET mutation. The latter is characterized by eosinophilic tumor cells and multiple chromosomal losses. These subtypes are responsible for 90-95% of all kidney cancers in adults. Additionally, rare tumor subtypes with unique immunohistochemical features, genetic abnormalities, or a specific clinical course may be identified. Currently, the RCC subtype only holds prognostic significance, and no treatment is associated with any subtype. However, therapies associated with histological subtypes may emerge in the future, and thus, the diagnosis of RCCs should be made following current recommendations.
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Carcinoma de Células Renales , Neoplasias Renales , Adulto , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Aberraciones Cromosómicas , Mutación , Antecedentes GenéticosRESUMEN
Urothelial cell carcinoma is the most common malignant tumor of the urinary tract, which develops in the renal pelvis, ureter, and bladder, and rarely it develops in the ureter. Histologically, urothelial cell carcinoma is categorized into non-invasive and invasive forms. Non-invasive urothelial cell carcinoma has papillary growth, it is usually well differentiated, and has a favorable outcome, while invasive urothelial cell carcinoma infiltratively spreads the organs of origin, it is typically poorly differentiated, and often associated with a poor prognosis. In the case of invasive urothelial cell carcinoma, the clinical course is primarily determined by the depth of invasion, but according to recent data, morphological variants of urothelial cell carcinoma respond differently to oncological treatments, and their biological behavior is also distinct. These subtypes and variants are significantly underdiagnosed in Hungary and internationally because the criteria for histological diagnosis are not clear for many subsets. The latest 2022 WHO classification of urinary tract tumors significantly clarified the definitions of various subtypes and variants. In this paper, utilizing the current classification, we review and explain these subtypes' morphological, immunohistochemical, differential diagnostic, prognostic, and predictive characteristics intending to make them appear as much as possible in everyday diagnostic practice. Also, the work aims to present the individual urothelial cell carcinoma subtypes and variants to the Hungarian community of pathologists, oncologists, and urologists, so that the previously high level of urological oncology care can become even more personalized. Orv Hetil. 2023; 164(40): 1567-1582.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Vejiga Urinaria , Hungría , Oncología MédicaRESUMEN
BACKGROUND: Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis. CASE PRESENTATION: Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors. CONCLUSIONS: We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs.
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Melanoma , Neoplasias del Pene , Neoplasias Cutáneas , Masculino , Humanos , Persona de Mediana Edad , Anciano , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/patología , Antígeno B7-H1 , Antígenos de NeoplasiasRESUMEN
Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival. Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary. FGFR3 mutations from the most infiltrative areas of the tumor were analyzed by targeted next-generation sequencing and PD-L1 (28-8 DAKO) tests (tumor positive score -TPS and combined positives score-CPS). In T0 cases FGFR3 mutations were analyzed from the earlier resection samples. Survival and oncological treatment data were collected from the National Health Insurance Fund (NHIF). Neoadjuvant, adjuvant and palliative conventional chemotherapies were allowed; immunotherapies were not. The relationship between the covariates was tested using chi-square tests, and survival analysis was performed using the Kaplan-Meier model and Cox proportional hazards regression. Results: PD-L1 and FGFR could be tested successfully in 215 of the 310 UBC samples [pT0cyst 19 (8.8%); St.0-I 43 (20%); St.II 41 (19%); St.III-IV 112 (52%)]. Significant pairwise dependency was found between tumor stage, FGFR3 mutation status and PD-L1 expression (p < 0.01). Samples with FGFR mutation were more common in less advanced stages and were also less likely to demonstrate PD-L1 expression. The effect of all investigated factors on survival was found to correlate with tumor stage. Conclusion: FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.
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Antígeno B7-H1 , Neoplasias de la Vejiga Urinaria , Humanos , Antígeno B7-H1/metabolismo , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patología , MutaciónRESUMEN
Chemotherapy for the treatment of urothelial and bladder cancers has focused on renewed indications in light of clinical trials of modern therapies, which are described in our review. In stage T2-T4a N0-1 M0 cases, that are suitable for cisplatin, surgery is performed after neoadjuvant cisplatin- based chemotherapy. Less significant result is observed with adjuvant chemotherapy, especially in pT3-4 and/or N+ stage, if no neoadjuvant chemotherapy was administered. Cisplatin-based chemotherapy is the first-line treatment of cisplatin-eligible metastatic patients. First-line choice in chemo-fit cases with cisplatin ineligibility can be carboplatin- based chemotherapy. 4-6 cycles of cisplatin or carboplatin cause stable disease or regression, maintenance avelumab immunotherapy improves patient's survival. For those patients who progress during or after platinum-based chemotherapy, the effectiveness of chemotherapy in the second/multiple lines is less favourable in comparison with immunotherapy and targeted therapy. Modern antibody - cytotoxic drug conjugates have been discovered in the form of enfortumab vedotin and sacituzumab govitecan, and currently they seem to be effective in the third line after chemotherapy and immunotherapy.
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Antineoplásicos , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Cisplatino/uso terapéutico , Humanos , Inmunoterapia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Xp11.2 translocation carcinoma is a distinct subtype of renal cell carcinoma characterized by translocations involving the TFE3 gene. Our study included the morphological, immunohistochemical and clinicopathological examination of 28 Xp11.2 RCCs. The immunophenotype has been assessed by using CA9, CK7, CD10, AMACR, MelanA, HMB45, Cathepsin K and TFE3 immunostainings. The diagnosis was confirmed by TFE3 break-apart FISH in 25 cases. The ages of 13 male and 15 female patients, without underlying renal disease or having undergone chemotherapy ranged from 8 to 72. The mean size of the tumors was 78.5 mm. Forty-three percent of patients were diagnosed in the pT3/pT4 stage with distant metastasis in 6 cases. Histological appearance was branching-papillary composed of clear cells with voluminous cytoplasm in 13 and variable in 15 cases, including one tumor with anaplastic carcinoma and another with rhabdoid morphology. Three tumors were labeled with CA9, while CK7 was negative in all cases. Diffuse CD10 reaction was observed in 17 tumors and diffuse AMACR positivity was described in 14 tumors. The expression of melanocytic markers and Cathepsin K were seen only in 7 and 6 cases, respectively. TFE3 immunohistochemistry displayed a positive reaction in 26/28 samples. TFE3 rearrangement was detected in all the analyzed cases (25/25), including one with the loss of the entire labeled break-point region. The follow-up time ranged from 2 to 300 months, with 7 cancer-related deaths. In summary, Xp11.2 carcinoma is an uncommon form of renal cell carcinoma with a variable histomorphology and rather aggressive clinical course.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/patología , Cromosomas Humanos X/genética , Reordenamiento Génico , Neoplasias Renales/patología , Adolescente , Adulto , Anciano , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/genética , Niño , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Our study aimed to analyze the potential association between clinical parameters and ERG expression and the outcome of docetaxel chemotherapy among patients with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: Fifty-five patients with metastatic hormone-sensitive prostate cancer were treated with docetaxel in addition to androgen deprivation therapy. Patient characteristics, clinical factors, and tumor expression of ERG by immunohistochemistry were analyzed with respect to therapeutic response and survival data. RESULTS: Relapse free survival (RFS) and overal survival (OS) were 10.5 and 40.4 months, respectively, and both correlated with PSA response (RFS: 16.8 with a ≥50% decrease in PSA vs. 5.9 months in the case of <50% decrease, P < 0.001; OS: 40.4 vs. 11.6 months, respectively, P < 0.001). There was an association between OS and early progression (OS: 40.4 months with progression after 12 months vs. 17.9 months with progression within 12 months, P = 0.009). ERG expression was detected in 21 (42%) samples. ERG positivity was associated with favorable RFS (ERG pos. vs. neg.: 26.0 vs. 11.4 months, P = 0.003). CONCLUSION: ERG expression may have a potential predictive value with respect to the effectiveness and outcome of docetaxel chemotherapy combined with androgen deprivation therapy.
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Antagonistas de Andrógenos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Adulto , Anciano , Antagonistas de Andrógenos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Docetaxel/farmacología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Regulador Transcripcional ERG/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Neuroendocrine neoplasms include a heterogeneous group of malignant tumors. Primary neuroendocrine tumors in the genitourinary tract are rare, comprising approximately 1-2% of genitourinary malignancies. MATERIALS AND METHODS: An extensive search was performed for publications between 2000 and 2018 regarding neuroendocrine tumors of the genitourinary tract. Epidemiological, clinical, histopathological, prognostic and therapeutic data were evaluated. RESULTS: Neuroendocrine tumors of the kidneys are exceedingly rare, mostly well-differentiated. 0.5-1% of all primary bladder malignancies are small cell neuroendocrine carcinomas. Characteristically, prostatic adenocarcinoma with neuroendocrine differentiation occurs in androgen receptor-independent/castrate-resistant cancer. Small cell and large cell neuroendocrine carcinomas are the most aggressive tumors in each location. CONCLUSION: Due to the rarity and poor prognosis of these tumors, proper pathological diagnosis and early therapy are important. Therapeutic guidelines are not available. Surgery, radiotherapy and/or chemotherapy are possible treatment options; somatostatin analogs are used as standard therapy in case of well-differentiated neuroendocrine tumors.