RESUMEN
INTRODUCTION: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. PATIENTS AND METHODS: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. RESULTS: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). CONCLUSION: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Cistectomía , Terapia Neoadyuvante , Resultado del Tratamiento , Quimioterapia Adyuvante , Estudios RetrospectivosRESUMEN
We describe 33 cases of myxoid pseudotumor involving the renal sinus from 31 patients. Patients included 21 men and 10 women, ages 30 to 95 years. Twenty-seven cases (82%) had an associated malignancy, including urothelial carcinoma of the renal pelvis (22 cases), clear cell renal cell carcinoma (3 cases), urothelial carcinoma of the bladder (1 case), and poorly differentiated carcinoma of uncertain lineage (1 case). The remaining 6 (18%) had no associated malignancy and included 3 nephrectomies for ureteral stricture, 2 ureteropelvic junction repairs, and 1 resection of a "periureteral mass" (subsequently shown to be myxoid pseudotumor). Myxoid pseudotumor was identified by preoperative computed tomography imaging in 2 patients (6%) and identified by the gross dissector in 9 cases (27%). The mean size was 14 mm (range: 5 to 38 mm). All cases had an admixture of adipocytes, myxoid stromal matrix, variable collagenization, and a hypocellular population of bland spindled and stellate stromal cells. No multilobated atypical stromal cells were present. Clinical follow-up was available for 28 patients (90%), ranging from 1 to 132 months (mean: 24.6 mo). No patients had adverse events related to the myxoid pseudotumor. Myxoid pseudotumor of the renal sinus is often associated with a variety of adjacent neoplastic and non-neoplastic conditions and may present as a mass lesion detectable by imaging and/or gross inspection. Awareness of this benign process is important to avoid confusion with a neoplasm, especially liposarcoma.
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Carcinoma de Células Transicionales , Liposarcoma , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Liposarcoma/patología , Vejiga Urinaria/patología , Pelvis Renal/patologíaRESUMEN
Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcystic features, 23 (55%) were stage pT3a or higher. Most tumors had strong and diffuse cytoplasmic immunoreactivity for CK7 (93%, 37/40) and AMACR (100%, 40/40). Fumarate hydratase staining was retained in all cases tested (39/39). We performed next-generation sequencing on 15 of these cases with available tissue and identified chromosomal alterations commonly reported in historically "type 1" PRCC, notably multiple chromosomal gains, particularly of chromosomes 7 and 17, and MET alterations. However, alterations in pathways associated with more aggressive behavior (including SETD2, CDKN2A, and members of the NRF pathway) were also identified in 6 of 15 cases tested (40%). Given this molecular and immunophenotypic data, we subsequently reviewed an additional group of 60 consecutive pT2b-pT3 PRCCs to allow for comparisons between cases with and without microcysts, to assess for potential associations with other recently described histologic patterns (ie, "unfavorable architecture": micropapillary, solid, and hobnail), and to assess interobserver reproducibility for diagnosing architectural patterns and grade. Of the total combined 102 PRCCs, 67 (66%) had microcystic architecture within the intrarenal component but were commonly admixed with other patterns (39% had micropapillary, 31% solid, and 31% hobnail). Twenty-seven cases (26%) had metastatic disease, and 24 of these 27 (89%) had microcystic architecture in the intrarenal tumor. Within the pT3 subset, 21 of 22 cases with metastases (95%) had extrarenal invasion as either individual microcysts in renal sinus fat or aggregates of microcysts bulging beyond the confines of the capsule. Backward elimination and stepwise regression methods to detect features significantly associated with adverse outcome identified solid architecture (hazard ratio [HR]: 6.3; confidence interval [CI]: 2.1-18.8; P=0.001), hobnail architecture (HR: 5.3; CI: 1.7-16.7; P=0.004), and microcystic architecture at the tumor-stromal interface (HR: 4.2; CI: 1.1-16.7; P=0.036) as strongest. Of architectural patterns and grade, the microcystic pattern had a substantial interobserver agreement (κ score=0.795) that was highest among the 6 observers. In summary, PRCCs with microcystic architecture represents a subset of historically "type 1" PRCC with a predilection for morphologically distinctive extrarenal involvement and metastatic disease. Microcysts co-vary with other "unfavorable" architectural patterns also associated with higher risk for aggressive disease (ie, micropapillary, hobnail, and solid), but microcysts were more common and have superior interobserver reproducibility. These findings suggest that microcystic PRCC should be recognized as a potentially aggressive histologic pattern of growth in PRCC.
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Carcinoma Papilar/patología , Carcinoma de Células Renales/patología , Quistes/patología , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Quistes/diagnóstico , Quistes/genética , Quistes/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Variaciones Dependientes del Observador , Pronóstico , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.
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Neoplasias de Células Germinales y Embrionarias , Cordón Espermático , Neoplasias Testiculares , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Estudios Retrospectivos , Cordón Espermático/patología , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapiaRESUMEN
We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease-associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high-molecular-weight cytokeratin, PAX8, and GATA3. Staining for alpha-methylacyl-CoA racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative alpha-methylacyl-CoA racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high-molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.
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Adenoma/patología , Carcinoma de Células Renales/patología , Proliferación Celular , Enfermedades Renales Quísticas/patología , Fallo Renal Crónico/patología , Neoplasias Renales/patología , Túbulos Renales/patología , Lesiones Precancerosas/patología , Adenoma/química , Adenoma/genética , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/química , Carcinoma de Células Renales/genética , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia , Inmunohistoquímica , Hibridación Fluorescente in Situ , Enfermedades Renales Quísticas/genética , Enfermedades Renales Quísticas/metabolismo , Fallo Renal Crónico/genética , Fallo Renal Crónico/metabolismo , Neoplasias Renales/química , Neoplasias Renales/genética , Túbulos Renales/química , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Valor Predictivo de las Pruebas , Estados Unidos , Adulto JovenRESUMEN
Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.
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Carcinoma de Células Transicionales/patología , Coriocarcinoma no Gestacional/patología , Trofoblastos/patología , Neoplasias Urológicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urotelio/patologíaRESUMEN
Solitary fibrous tumour (SFT) is well-described in the urinary tract, but malignant examples are rare. We studied our experience with high grade malignant SFT of the prostate to address the degree of histological and immunophenotypical overlap with sarcomatoid carcinoma and prostatic stromal sarcoma. Four cases were identified from the surgical pathology consultation archives. All available H&E stained sections were reviewed. Immunostains for STAT6, CAM5.2, NKX3.1, PAX-8, GATA3, high molecular weight cytokeratin (34BE12), p40, and p63 were performed on available material. Each case was evaluated by three separate SFT prognostic risk models based on clinicopathological features, and for features of 'dedifferentiated SFT'. The patient's ages were 49, 55, 69, and 73 years. Three presented with symptoms of benign prostatic hyperplasia and one with haematuria. Tumour sizes were 5, 9, 13, and 13 cm. Mitotic rate ranged from 6 to 20 mitoses per 10 high power fields, and two cases showed abrupt transition from conventional SFT to areas with marked nuclear pleomorphism/anaplasia (i.e., 'de-differentiation'). Immunophenotypically, all four cases had strong and diffuse nuclear reactivity for STAT6. For other markers, three of three had both focal PR and GATA3 nuclear expression (up to 30% of cells). One case with 'dedifferentiated' features showed expression of multiple epithelial markers, including EMA (focal), high molecular weight cytokeratin (focal), p63, and p40. In summary, malignant SFT may rarely occur in the prostate and may closely mimic sarcomatoid carcinoma or prostatic stromal sarcoma, both histologically and immunophenotypically. Consideration of the diagnostic possibility of malignant SFT, recognition of unexpected GATA3 and PR expression, and utilisation of monoclonal STAT6 immunohistochemistry facilitate appropriate diagnosis at this unusual anatomical site.
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Biomarcadores de Tumor/análisis , Carcinoma/diagnóstico , Neoplasias de la Próstata/diagnóstico , Sarcoma/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico , Anciano , Carcinoma/patología , Femenino , Factor de Transcripción GATA3/metabolismo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Pronóstico , Próstata/patología , Neoplasias de la Próstata/clasificación , Neoplasias de la Próstata/patología , Factor de Transcripción STAT6/metabolismo , Sarcoma/patología , Tumores Fibrosos Solitarios/clasificación , Tumores Fibrosos Solitarios/patologíaRESUMEN
AIMS: Invasive micropapillary carcinoma is a recognised aggressive urothelial carcinoma variant. One prior study focusing on non-invasive (pTa) high-grade papillary urothelial carcinoma with micropapillary architecture has been reported. METHODS AND RESULTS: We collected bladder transurethral resection specimens showing non-invasive high-grade papillary urothelial carcinoma with non-hierarchical secondary papillae lacking fibrovascular cores (i.e. micropapillary architecture). Cases with any invasive component or any prior history of invasive urothelial carcinoma were excluded. Twenty cases were identified from 16 male and two female patients (aged 55-86 years). Micropapillary architecture comprised from 10 to 95% (mean = 31%), but non-invasive cribriform (15 cases, comprising 5-60%, mean = 19%) and villoglandular patterns (nine cases, comprising 5-60%, mean = 24%) were commonly admixed. Treatment data were available for 16 patients: surveillance (n = 13), cystoprostatectomy (n = 1), BCG plus mitomycin (n = 1) and BCG (n = 1). Follow-up data were available from 16 patients (range = 1-128 months, mean = 50 months): 13 patients had no new occurrences to date (81%), two had stage progression to pT1 papillary urothelial carcinoma (13%) with one dying of other causes, and one died of other causes with no evidence of disease (6%). CONCLUSION: Non-invasive urothelial carcinomas with micropapillary architecture are often admixed with non-invasive cribriform and villoglandular patterns. Stage progression to lamina propria invasion in only two of 16 patients (13%) is not higher than expected for otherwise typical pTa high-grade urothelial carcinomas and no progression to invasive micropapillary carcinoma was identified, adding further support to the current World Health Organisation recommendation excluding use of the term 'micropapillary' for pTa urothelial carcinoma.
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Carcinoma Papilar/patología , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/mortalidad , Carcinoma de Células Transicionales/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
Renal cell carcinoma with (angio) leiomyomatous stroma (RCCLMS) is included as a provisional entity in the 2016 World Health Organization (WHO) classification of renal epithelial neoplasia; however, debate remains whether it represents a distinct entity or a heterogenous group of renal cell carcinomas (RCCs) with overlapping morphology. Also, its relationship to similar tumors occurring in the setting of tuberous sclerosis complex (TSC) is not fully addressed. We analyzed the clinicopathologic, immunohistochemical, and molecular characteristics of 23 sporadic RCCs associated with smooth muscle stroma and classified them into 2 groups, independent of molecular results: (1) RCCLMS (n=18) and (2) clear cell renal cell carcinoma (CCRCC) (n=5). The classification of a case as "RCCLMS" was based on morphologic comparison with 5 "index" RCCs from 3 patients with TSC showing similar features and the presence of diffuse CK7 expression. To investigate mutational and copy number alterations, a 170-gene solid tumor panel was utilized to sequence 14 RCCLMSs and control of 5 CCRCCs. Also, 4 RCCLMSs, suspicious for chromosome 8 monosomy, were further evaluated by a broader 479 gene sequencing panel that included ELOC (also referred to as TCEB1). Clinical information and follow-up data were obtained from electronic medical records. The mean age of patients with RCCLMS was 52 years (range, 33 to 69) with male:female ratio of 1:2. Macroscopically, all tumors were solitary and predominantly (82%) tan/red, circumscribed, and solid. The average tumor size was 2.3 cm (range, 1.1 to 4.5). Microscopically, the distinctive feature included tumor nodules of elongated and frequently branching tubules lined by cells with voluminous clear to mildly eosinophilic cytoplasm (100%), separated by focal to prominent smooth muscle stroma. Additional frequently identified features included: biphasic pattern of collapsed acini surrounding tubules with voluminous cytoplasm (50%), focal papillary architecture (39%), peritumoral lymphoid aggregates (39%), and hemosiderin-laden macrophages (33%). All 11 (100%) RCCLMSs with available staging information were pT1; 78% were WHO/International Society of Urologic Pathology (ISUP) grade 2 and 22% grade 3. Immunophenotypically, RCCLMSs were characterized by diffuse CK7, CAM5.2 and CD10 reactivity (100%). All patients with available follow-up (n=10) were alive and without disease progression after a mean and median follow-up of 25.2 (range: 1 to 58) and 25 months, respectively. The molecular results showed recurrent mutations in all RCCLMS: TSC1 (4), TSC2 (4), MTOR (6), and/or ELOC (2). Five control CCRCCs demonstrated primary alterations in VHL gene, while all 14 RCCLMS cases tested had intact VHL gene. Of 2 RCCLMSs with confirmed monosomy 8, 1 showed a hotspot ELOC mutation without TSC/MTOR mutations, and 1 showed a previously undescribed 3-bp in-frame ELOC deletion, along with a truncating TSC1 mutation. In conclusion, RCCLMS, as defined herein, harbors recurrent mutations of TSC1/TSC2, MTOR, and/or ELOC, consistent with hyperactive MTOR complex. Our findings argue that these tumors represent the sporadic counterpart to morphologically identical tumors occurring in TSC patients. Finally, the data support that RCCLMS is a novel subtype of RCC with unique morphologic, immunohistochemical, and molecular characteristics that is distinct from CCRCC and clear cell-papillary RCC.
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Angiomioma/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Elonguina/genética , Neoplasias Renales/genética , Mutación , Serina-Treonina Quinasas TOR/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Adulto , Anciano , Alberta , Angiomioma/patología , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Ohio , Fenotipo , Supervivencia sin Progresión , Células del Estroma/patología , Terminología como AsuntoRESUMEN
AIMS: Intraductal proliferations of the prostate with more complexity and/or cytological atypia than high-grade prostate intra-epithelial neoplasia (HGPIN), but falling short of intraductal carcinoma (IDC-P), are described as 'atypical intraductal proliferation' (AIP). When present in needle biopsy (NBX) without IDC-P, the clinical significance is not known. METHODS AND RESULTS: Sixty-two NBX cases were diagnosed as AIP over 7 years with estimated incidence of 1%. AIP was characterised by loose cribriform architecture (90%) or non-cribriform architecture exhibiting significant nuclear atypia that fell short of IDC-P. Fifty patients had concomitant PCa (20% grade group (GG) 1, 48% GG2, 14% GG3, 8% GG4 and 10% GG 5), and 12 had AIP alone. Of 40 patients who were candidates for no therapy (AIP alone) or active surveillance (AIP with GG1 or GG2 PCa without cribriform pattern 4), 20 had subsequent follow-up pathology [seven NBXs and 13 radical prostatectomy (RP)]. Of the 12 AIP only patients, six had a subsequent biopsy diagnosis of: benign prostate (two), IDC-P with PCa (one) and PCa (three). One or more adverse pathological features at subsequent RP were present in 93% of patients with AIP and GG1 or GG2 PCa, defined as: GG ≥ 3 (15%), IDC-P (77%), cribriform Gleason pattern 4 (69%), pT3a (77%) or pT3b (8%). CONCLUSIONS: AIP in NBX may be a marker of unsampled IDC-P and/or other adverse pathological features in suspected low- to intermediate-risk PCa. AIP should be considered distinct from HGPIN for risk assessment and warrant consideration for further work-up to detect unsampled high-risk PCa.
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Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Immunohistochemistry may be a very useful adjunct to morphologic diagnosis in many areas of surgical pathology, including genitourinary pathology. In this review, we address common diagnostic dilemmas where immunophenotypic analysis may be utilized and we highlight pitfalls specific to each scenario. For prostate, we review the diagnosis of limited prostatic adenocarcinoma and the distinction of high-grade prostatic adenocarcinoma from urothelial carcinoma. We also cover markers of urothelial lineage in the diagnosis of metastatic carcinoma of unknown primary site. In the kidney, distinction of poorly differentiated renal cell carcinoma from urothelial carcinoma and epithelioid angiomyolipoma, adjuncts to the recognition of hereditary renal neoplasia, and the diagnosis of metastatic renal cell carcinoma are discussed. Finally, for testis we address distinction of germ cell tumors from sex cord-stromal tumors, as well as the diagnosis of metastatic germ cell tumors.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/diagnóstico , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Urotelio/patología , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Urotelio/metabolismoRESUMEN
The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic disease (ACD)-associated RCC was recently incorporated into the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Tract as a distinct entity and is reportedly the most common RCC arising in end-stage renal disease. In this study, we sought to further describe clinicopathologic findings in a large series of ACD-RCC, emphasizing histologic features, immunophenotype, clinical outcome, and patterns of disease spread. We collected 40 previously unpublished cases of ACD-RCC with mean clinical follow-up of 27 months (median, 19 mo; range, 1 to 126 mo). Mean tumor size was 2.7 cm (median, 2.4 cm), and 32 tumors (80%) were confined to the kidney (pT stage less than pT3a). International Society of Urological Pathology grade was 3 in 37 cases (92.5%), grade 2 in 1 case (2.5%), and grade 4 in 2 cases (5%). Architectural variability among ACD-RCC was common, as 39 cases (98%) showed varying combinations of tubular, cystic, solid, and/or papillary growth. ACD-RCC frequently occurred in association with other renal tumor subtypes within the same kidney, including papillary RCC (14 patients), papillary adenomas (7 cases), clear cell papillary RCC (5 cases), clear cell RCC (1 case), and RCC, unclassified type (1 case). A previously undescribed pattern of perinephric and renal sinus adipose tissue involvement by dilated epithelial cysts with minimal or absent intervening capsule or renal parenchyma was identified in 20 cases (50%); these cysts were part of the tumor itself in 5 cases (25%) and were part of the non-neoplastic acquired cystic change in the background kidney in the remaining 15 cases (75%). Of the 24 cases (60%) with tissue available for immunohistochemical stains, 19 (79%) were positive for PAX8, 20 (83%) showed negative to patchy expression of cytokeratin 7, and 24 (100%) were both positive for AMACR and negative for CD117. Fumarate hydratase expression was retained in all tumors, including those with nuclear features resembling fumarate hydratase-deficient RCCs. Of the 36 patients (90%) with available follow-up information, 4 (11%) experienced adverse events: 2 patients developed a local recurrence, 1 patient experienced multiple visceral metastases and subsequently died of disease, and 1 patient developed metastases to regional lymph nodes only. One local recurrence and the lymph node only metastasis both had an unusual, exclusively cystic pattern of growth. In summary, we present the largest clinicopathologic series of ACD-RCC to date and describe previously unreported cystic patterns of local soft tissue involvement and recurrence/metastases.
Asunto(s)
Carcinoma de Células Renales/patología , Enfermedades Renales Quísticas/patología , Neoplasias Renales/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52-year-old woman was diagnosed with invasive melanoma (Breslow thickness 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with 2 morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB-45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB-45 and SOX-10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.
Asunto(s)
Melanoma/diagnóstico , Melanoma/patología , Mioblastos/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Biomarcadores de Tumor/análisis , Desdiferenciación Celular , Femenino , Humanos , Persona de Mediana Edad , Melanoma Cutáneo MalignoRESUMEN
Wilms tumor, the most common kidney tumor in children, is rarely seen in adults, making it a challenge for the adult oncologist to diagnose and treat. Unlike with renal cell carcinoma, patients with Wilms tumor should receive adjuvant chemotherapy with or without radiation therapy. Adult oncologists may not be familiar with pediatric oncology protocols, so it is important to consult with pediatric oncologists who have more experience in this disease. Multimodal therapy based on pediatric protocols improved the outcomes of adults with Wilms tumor worldwide. We report a rare case of a 24-year-old woman with a slow-growing mass of the left kidney during a 4-year period. The mass was surgically removed and final diagnosis confirmed by pathology to be Wilms tumor. The patient received adjuvant chemotherapy and has been free of disease since 2014.
Asunto(s)
Neoplasias Renales , Tumor de Wilms/diagnóstico , Femenino , Humanos , Hallazgos Incidentales , Tumor de Wilms/fisiopatología , Adulto JovenRESUMEN
Paraganglioma of the urinary bladder is an uncommon clinical entity. Neuroblastoma of the urinary bladder is another rare tumor with only 7 reported cases, all in children. This report presents the case of a composite paraganglioma and neuroblastoma in a 45 year-old male who presented with dysuria and flank pain. On the computerized tomography scan, the bladder wall overlying the tumor was smooth and the mass had a large exophytic component. The initial diagnosis was paraganglioma on transurethral resection. Following partial cystectomy and bilateral pelvic lymph node dissection, pathology confirmed a composite tumor consisting of paraganglioma and neuroblastoma. To our knowledge, this is the first report of such a composite tumor involving the bladder.
RESUMEN
OBJECTIVES: Mixed Epithelial and Stromal Tumor of the kidney is an adult renal neoplasm. It is mostly benign in nature. Typically it is composed of a mixture of epithelial and mesenchymal components. We hereby report on the feasibility of performing partial nephrectomy/enucleation for Huge Mixed Epithelial Stromal Tumor of the kidney without sacrificing the involved renal unit even in the tumors herniating into the collecting system. METHODS: Two female patients on long term hormonal therapy developed large enhancing multiloculated and septated renal masses. Kidney mass size was 18.5 cms in one patient and 11.5 in the second. In one patient, the mass was herniating into the collecting system. Both patients had enucleation/partial nephrectomy. RESULTS: Enucleation and partial nephrectomy were successfully performed in both patients. In the patient with the mass herniating into the collecting system, the horns of the mass herniating into the collecting system were easily enucleated with repair of the collecting system and salvage of the involved renal unit. Post op pathology revealed MEST in both patients. There were no intraoperative or postoperative complications. CONCLUSIONS: Enucleation and partial nephrectomy for huge MEST is feasible. Mixed Epithelial Stromal Tumor herniating into the pelvicalyceal system may not warrant nephroureterectomy as previously reported.
RESUMEN
The pseudoangiosarcomatous pattern has been described mostly in cutaneous and some visceral squamous cell carcinomas and is unique for its striking morphologic resemblance to angiosarcoma. Herein, we describe the clinicopathologic features of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87 years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7 urothelial carcinomas including 3 with squamous differentiation and comprised 35% to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous carcinomas were characterized by tumor cell discohesion and lysis that created pseudolumina formations surrounded by attached residual tumor cells. Detached degenerating tumor cells variably admixed with inflammatory cells were common in the false lumina. Partly intact urothelial carcinoma nests contained irregular or cleft-like spaces and disintegrating tumor cells with stretched intercellular bridges. The tumor was commonly associated with a dense collagenous matrix, often surrounding the lytic nests. Similar tumor cell discohesion and breakdown were observed in 3 tumors with foci of squamous cell differentiation, distinguished by the presence of dyskeratosis and keratin formation. All 7 tumors contained other nonpseudoangiosarcomatous carcinoma components such as conventional urothelial carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma (2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all (7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7) expressed vascular-associated markers. There was no evidence to suggest that apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell discohesion and breakdown. All 7 tumors were high stage at cystectomy and included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node involvement. Follow-up data available in 6 cases revealed a poor outcome with an overall median survival of 8.5 months. In conclusion, we present an unusual morphology of bladder carcinoma that has a striking resemblance to a malignant vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous carcinoma morphology is associated with a higher tumor stage at cystectomy, commonly admixed with other aggressive carcinoma variant morphologies, and portend a poorer outcome. Knowledge of this pattern is also important to avoid misdiagnosis, particularly in limited tissue samples.
Asunto(s)
Carcinoma/patología , Hemangiosarcoma/patología , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma/química , Carcinoma/clasificación , Carcinoma/mortalidad , Diferenciación Celular , Femenino , Hemangiosarcoma/química , Hemangiosarcoma/clasificación , Hemangiosarcoma/mortalidad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Terminología como Asunto , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/clasificación , Neoplasias de la Vejiga Urinaria/mortalidad , Urotelio/químicaRESUMEN
Papillary cystadenoma is an uncommon epithelial tumor, originating within the head of the epididymis and broad ligament. When the lesion is bilateral, it is associated with von Hippel-Lindau disease. Its resemblance to metastatic clear cell renal cell carcinoma (RCC) has been noted in the literature. Owing to the emergence of additional markers for RCCs, we have evaluated the immunohistochemical staining patterns of a series of 7 papillary cystadenomas using CK7, RCC, PAX8, carbonic anhydrase IX, and AMACR. Six of the cases involved the epididymis, and 1 involved the broad ligament. The patients ranged in age from 20 to 65 years old. All of the tumors were unilateral and not known to be associated with von Hippel-Lindau disease. The lesions were composed of cystic structures, which focally contained papillary fibrovascular cores lined by cuboidal to columnar bland-appearing cells with clear cytoplasm. Another component was the presence of tubules, which focally had elongated profiles. Reverse polarity, wherein the nuclei are oriented toward the luminal surface with subnuclear vacuoles, was present focally in 4 cases and more extensively in a fifth case. Features associated with malignancy, such as mitotic figures, nuclear pleomorphism, and necrosis, were not identified. All lesions were strongly positive for CK7 and negative for RCC. Carbonic anhydrase IX was positive in all tumors (diffusely positive in 6, patchy in 1) with lack of staining in the apical portion of the cytoplasm (ie, cup-shaped staining). PAX8 showed diffuse positivity in 6 of the 7 lesions, with one of the epididymal cases showing negative staining. AMACR staining was negative in 5 of the 7 cases and showed only focal, weak staining in the remaining 2 cases. The current study more specifically demonstrated that papillary cystadenoma does not resemble clear cell RCC. Rather, papillary cystadenomas of the epididymis and broad ligament have identical morphology and immunohistochemical staining to clear cell papillary RCC. The diagnosis of papillary cystadenoma can be established as clear cell papillary RCC to date has not exhibited metastatic behavior.
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Ligamento Ancho/patología , Cistoadenoma Papilar/patología , Epidídimo/patología , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Masculinos/diagnóstico , Adulto , Anciano , Biomarcadores de Tumor/análisis , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Cistoadenoma Papilar/metabolismo , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We describe a rare pattern of urothelial carcinoma (UC) invasion consisting of large, irregular to regular nests, with bland cytology. We prospectively retrieved 23 cases of large nested UC from one of the author's consult files (2001 to 2010). The mean patient age was 63.7 years (39 to 89 y), and 86% were men. There were 18 cases with transurethral resection of the bladder, 2 nephroureterectomy specimens, and 3 radical cystectomy (RCs) specimens. A surface component was present in 19 of 23 cases, with 16 low-grade papillary UCs, 2 low-grade papillary UCs with <5% high-grade UC, and 1 high-grade papillary UC. Twenty of 23 cases invaded into the muscularis propria (MP), 2 into lamina propria with no MP present, and 1 into smooth muscle indeterminate between muscularis mucosae and MP. In 21 cases, the invasive component was composed of medium to large nests that varied from rounded circumscribed borders to a stromal-tumor interface with a more irregular ragged appearance. Two showed a verruciform, pushing border into the MP with the nests having central cyst formation. Cytologically, the nuclei lacked significant nuclear atypia, where at most occasional scattered slightly enlarged, hyperchromatic nuclei with small-indistinct nucleoli were noted. Four cases had focal necrosis and 3 cases had more extensive necrosis. The median mitotic count was 1.5 per 10 high-power fields. The stroma surrounding the large nests typically had a mild-to-moderate fibrous and/or inflammatory reaction; 4 cases exhibited no stromal reaction, whereas 2 cases had a moderate-to-marked stromal response. In 7 of 23 cases, conventional patterns of urothelial invasion were identified, 5 of which composed ≤5% of the neoplasm. One case had angiolymphatic invasion. Four cases had subsequent RC specimens available for review. Two of 4 RC specimens had no residual carcinoma (1 with neoadjuvant radiotherapy), 1 had large nested UC in MP, and 1 had mixed large nested UC and focal conventional UC invading through the MP into perivesicle tissue. Clinical follow-up was available for 17 of 23 patients [mean follow-up, 43 mo (5 mo to 9 y)]. Three of 17 patients developed metastatic disease (2 lung, 1 unknown) with 2 of these dead of disease; another patient was dead of disease with no known details. Of these 3 patients that died of disease, 2 had no and 1 had focal (<5%) conventional invasive UC on transurethral resection. These cases, which posed great diagnostic difficulty both for contributing pathologists and for the consultant, represent the first formal description of a large nested pattern of UC. This pattern is distinguished from an inverted growth pattern of noninvasive UC and from von Brunn nests by either MP invasion, irregularly infiltrating nests, or a stromal reaction. Despite the bland cytologic features of these neoplasms, they have well-documented metastatic potential.