Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy1–8. However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape. The authors examine the immune cell infiltrates of human tumours and provide evidence for a population of CD8 T cells with stem-cell characteristics and proliferative capacity that reside in an antigen-presenting niche within tumours.

Introduction: About 10% of tumors derived from nongynecologic, noncoelomic tissues react with the OC125 antibody. Some patients with advanced prostate cancer were found to have elevated serum CA-125 level.Materials and methods: We examined the clinical history of 11 patients with castration resistant prostate cancer and an elevated serum CA-125 level. Pathological review and immunohistochemical staining were performed on tumors from eight of these patients.Results: Patients with advanced prostate cancer and an elevated serum CA-125 level responded to androgen ablative therapy (median duration, 27 months). They were predisposed to develop persistent or recurrent urinary symptoms and visceral metastases. Eight of 11 patients had a low or undetectable serum prostate-specific antigen level (<= 4 ng/mL) or an elevated serum carcinoembryonic antigen level (> 6 ng/mL). In 3 of 7 patients whose specimens were available for further review, the tumors contained histologic features compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate.Conclusions: Patients with prostate cancer and an elevated serum CA-125 level have unique clinical and pathologic characteristics. Some of these patients possess tumors compatible with a subtype of prostate cancer known as ductal adenocarcinoma. Additional studies need to be performed to elucidate the biologic basis of the various subtypes of prostate cancer.

Ewing sarcoma (ES) is an aggressive malignant small round cell tumor that arises in bone or soft tissue of adolescents and young adults. A characteristic molecular finding in ES is EWSR1 gene fusion with ETS (erythroblast transformation-specific) family genes including FLI1 (~90%) and ERG (>5%). Here we report our experience using integrated clinicopathologic, cytogenetic, fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of 32 pediatric patients with ES diagnosed in a single institution between 2005 and 2011. Diagnostic EWSR1 rearrangements were detected in 30 (93.8%) of 32 patients. Cytogenetics detected t(11;22) (n = 14) and t(21;22) (n = 1) in 15 (46.9%) patients. FISH detected EWSR1 rearrangements in 27 (96.4%) of 28 patients tested. RT-PCR was positive in 27 (84.4%) of 32 patients, including 24 EWSR1-FLI1 and 3 EWSR1-ERG. RT-PCR defined breakpoints and fusion partners in 7 cases with EWSR1 rearrangements detected by FISH. Sanger sequencing further delineated breakpoints in 21 (77.8%) of 27 RT-PCR positive cases. In summary, conventional cytogenetic analysis provided a global view but had a lower detection rate and longer turnaround time than other methods. FISH is a rapid method and theoretically can detect all EWSR1 rearrangements, but it cannot identify all partners and is not completely specific for ES. RT-PCR and sequencing are more sensitive and useful in identifying fusion partners and refining breakpoints; however, these methods can be compromised by poor RNA preservation and primer design. In conclusion, an integrated approach that uses all methods capable of detecting EWSR1 rearrangements has value in the workup of suspected cases of ES.

Aims: We present 51 cases of primary small cell carcinoma of the bladder in a clinicopathological study with emphasis on features that aid in the initial recognition and diagnosis of small cell carcinoma of the bladder.Methods and results: The patients were 40 men and 11 women between the ages of 39 and 87 years (mean age 67 years). Clinical data were available in 41 cases. The most common symptomatology was haematuria in 63% of the patients while dysuria was present in 12%. Thirty-eight patients were caucasians; seven patients were Hispanics; two patients were Asian; one patient was African-American; in the three additional patients no racial information was obtained. Biopsy material was obtained in all of the patients. Cystectomy was performed in 20 patients. At diagnosis, clinical stage was as follows: stage I in two (5%), stage II in 18 (44%), stage III in 10 (24%), and stage IV in 11 (27%). Histologically, urothelial carcinoma was present in 70% of the cases, adenocarcinoma in 8%, and squamous cell carcinoma in 10% of the cases. Small cell carcinoma was the only histology present in only 12% of the cases studied. Immunohistochemical studies using chromogranin, synaptophysin and chromogranin were positive in 30-70% of the cases.Conclusions: The present study highlights the unusual phenomenon of pure small cell carcinoma of the bladder and its association with other non-small cell carcinomas in that anatomical location. In addition, the study highlights the different modalities employed to treat patients in whom there is a component of small cell carcinoma of the bladder.

A case of primary, prostatic, low-grade neuroendocrine carcinoma (carcinoid tumor) is described. The patient is an 86-year-old man who presented with symptoms of gross hematuria of several days' duration. Physical examination and a bladder biopsy specimen revealed the presence of a primary adenocarcinoma of the bladder with invasion into the muscularis propria. A cystoprostatectomy was performed, which revealed the presence of invasive adenocarcinoma of the bladder. Prostatic sampling demonstrated the presence of a low-grade neuroendocrine carcinoma (carcinoid tumor) and a small focus of well-differentiated conventional adenocarcinoma. Immunohistochemical studies using neuroendocrine markers clearly demarcated the presence of the neuroendocrine tumor. The case presented herein highlights the ubiquitous distribution of neuroendocrine neoplasms along the male genitourinary tract and the presence of 3 separate neoplasms in the genitourinary tract.

You have accessJournal of UrologyDiscussed Poster, Monday, May 10, 2004, 8:00am - 12:00 pm1 Apr 2004791: Risk Factors for Progression of Prostatic Cancer with Seminal Vesicle Invasion Atsushi Ochiai, Adriana Reyes, Richard J. Babaian, and Patricia Troncoso Atsushi OchiaiAtsushi Ochiai More articles by this author , Adriana ReyesAdriana Reyes More articles by this author , Richard J. BabaianRichard J. Babaian More articles by this author , and Patricia TroncosoPatricia Troncoso More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)38040-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "791: Risk Factors for Progression of Prostatic Cancer with Seminal Vesicle Invasion." The Journal of Urology, 171(4S), pp. 209–210 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 209-210 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Atsushi Ochiai More articles by this author Adriana Reyes More articles by this author Richard J. Babaian More articles by this author Patricia Troncoso More articles by this author Expand All Advertisement PDF downloadLoading ...

We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohisto-chemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12–60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.

We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohistochemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12-60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.

Despite the proximity, prostate carcinoma seldom metastasizes to the penis or testis.

PURPOSE: To determine the activity and toxicity of doxorubicin in combination with cisplatin and etoposide in patients with small-cell prostate carcinoma (SCPCa) and to characterize the clinicopathologic features of SCPCa. PATIENTS AND METHODS: Patients with SCPCa (pure or mixed), measurable disease, good organ function, and no prior treatment with doxorubicin, etoposide, or cisplatin were treated every 4 weeks with doxorubicin 50 mg/m2 as a 24-hour intravenous (IV) infusion followed by etoposide 120 mg/m2/d and cisplatin 25 mg/m2/d IV on days 2 to 4. RESULTS: Thirty-eight patients (36 assessable for response) were treated for a median of four cycles. Twenty-nine (81%) of 36 patients had prior hormonal therapy. Study patients had visceral metastases, lytic bone disease, and relatively low serum prostate-specific antigen (PSA). We observed 22 partial responses (response rate, 61% in an intent-to-treat analysis); toxicity was severe (grade 3 or 4 neutropenia 100%, thrombocytopenia 66%, mucositis 21%, and infection 68%). Three patients died of toxicity. Median time to progression and overall survival time were 5.8 months and 10.5 months, respectively. Performance status, serum albumin, and number of organs involved (but not PSA, carcinoembryonic antigen, or neuroendocrine markers) were predictors of survival. CONCLUSION: SCPCa presents unique clinicopathologic features. Addition of doxorubicin to the etoposide/cisplatin regimen caused higher toxicity in this patient population and failed to improve outcome. Given these results, we do not recommend further development of this regimen for patients with SCPCa. Improvement in therapy will come from understanding the biology of SCPCa progression and integrating new targeted therapies into the treatment of SCPCa.

The false-positive interpretation of malignancy is a potential pitfall of exfoliative respiratory tract cytopathology. However, the underlying causes of this problem are still relatively under-recognized. The authors herein present two additional examples in which bronchial brushing and washing specimens were misinterpreted as showing carcinoma of the lung. The first case concerned a patient with a granulomatous mass that simulated a malignancy on chest radiographs and was the apparent cause of atypical bronchial squamous metaplasia (ABSM). Exfoliated cells from the latter process were thought to explain the false-positive cytologic result in that instance. In the second case, a large-cell angiocentric T-cell lymphoma replaced the lower lobe of the left lung. It was likewise associated with ABSM as the cause of a mistaken diagnosis of carcinoma in exfoliative respiratory cytology specimens, representing the first instance of such an association of which the authors are aware. Repeated evaluation of all bronchial cytology samples by several experienced pathologists yielded no reliable observations that might have been used to avoid an erroneous interpretation in either case. A review is provided of the spectrum of underlying conditions that may be associated with false-positive respiratory cytology results.