Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

Primary Extra-Osseous Ewing Sarcoma of the Thyroid: A Case Report and Review of the Literature.

Extra-osseous Ewing sarcoma (ES) is a rare and aggressive malignant tumor found in a variety of organs. Primary ES of the thyroid is exceedingly rare and few cases have been documented to date. We describe the case of a 54-year old woman with a history of breast carcinoma in whom a unique hypermetabolic left thyroid nodule was identified during a follow-up PET-CT scan. An ultrasound examination showed a hypoechogenic nodule of 3.7 cm. A cytological diagnosis of poorly differentiated thyroid carcinoma was made, and a total thyroidectomy was performed. The surgical specimen revealed a poorly differentiated neoplasm composed of medium-sized cells with scant cytoplasm, expressing pancytokeratin, CD99 and NKX2.2 but lacking p63 and p40 expression. Molecular analysis revealed a EWSR1-FLI1 fusion transcript supporting the diagnosis of a primary extra-osseous ES of the thyroid. The patient received adjuvant chemotherapy and has no evidence of recurrent disease.

Sustained response to pembrolizumab without prior chemotherapy in high-grade serous ovarian carcinoma with CSMD3 mutation.

•Metastatic CSMD3 mutated HGSOC showed objective and sustained response to pembrolizumab.•The tumor was massively infiltrated by CD8+ T cells while PD-L1 TPS was at 10%.•CSMD3 mutated HGSOC showed up-regulation of CCL5 and CXCL9.

Genetic profile of ductal adenocarcinoma of the prostate.

Despite being discovered almost 50 years ago, little is known regarding the genetic profile of ductal adenocarcinoma of the prostate (DAC). In recent years, progress has been made in the understanding of the genetics of acinar adenocarcinomas, and at least 7 genetically different subtypes have been identified. DAC is known to present at an advanced stage with a high rate of extraprostatic extension and seminal vesicle invasion, and a decreased interval to biochemical recurrence and the development of metastatic disease when compared with acinar adenocarcinoma. Our aim was to investigate the genetic profile of DAC to determine whether there is a genomic rationale for the aggressive behavior associated with this tumor type. Frozen tissue from 11 cases of DAC with paired benign tissue was analyzed. After DNA extraction, copy-number alteration analysis was performed, as well as identification of mutations and indels. We compared the fraction of the DAC genome with copy-number alteration to previous results from 74 primary acinar adenocarcinomas of the prostate. The alteration rate in DAC was comparable to that of acinar adenocarcinoma of high Gleason score. DAC harbored somatic changes seen in advanced and/or metastatic castration-resistant acinar adenocarcinoma, which likely accounts for its aggressive biological behavior.

Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features.

Ductal adenocarcinoma of the prostate (DAC) is recognised as a subtype of prostatic adenocarcinoma, but its diagnostic criteria and biology remain controversial. DAC was first thought to stem from Müllerian duct remnants, but further studies suggest a prostatic origin. DAC is composed of tall, columnar, pseudostratified epithelium with a papillary, cribriform, glandular or solid architecture. The diagnosis is based on morphology alone with papillary architecture being the most helpful diagnostic feature. The tumour is rare in a pure form and most cases are combined with acinar adenocarcinoma. The most common differential diagnoses of DAC are intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia. Patients often present at an advanced clinicopathological stage. High rates of extra-prostatic extension, seminal vesicle invasion, local and regional metastases, and positive surgical margins are seen after radical prostatectomy. DAC metastasises to sites that are less commonly seen for prostate cancer such as lung, brain, testis and penis. The morphology and the unusual metastatic locations make the accurate diagnosis of metastases challenging, but a positive immunostain for prostate specific markers may be helpful. The correct identification of DAC has implications for treatment as well as outcome.

Immunohistochemistry of ductal adenocarcinoma of the prostate and adenocarcinomas of non-prostatic origin: a comparative study.

Ductal adenocarcinoma of the prostate (DAC) has morphological similarities to adenocarcinomas of other organs. DAC behaves in an aggressive manner and may present with metastases. These metastases may occur at unusual sites, which itself may cause diagnostic difficulties. It is important for therapeutic decisions that a prostatic origin of these metastases be established. Our aim was to compare the protein expression of DAC and adenocarcinomas of colon, endometrium, lung, pancreas, stomach and urinary bladder. A tissue microarray was constructed using 60 DAC, 6 colonic, 7 endometrial, 7 lung, 5 pancreatic, 5 gastric, and 9 urinary bladder adenocarcinomas. Slides were stained for estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-Myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, and PAX-8. Androgen receptor, prostein, PSA, and PSAP were almost invariably expressed in DAC. Ki-67-labeling index was lower in DAC than in other adenocarcinomas. The expression patterns of intestinal markers and cytokeratins in DAC were less specific and may lead to diagnostic errors if not combined with prostate-specific markers.

Immunohistochemical profile of ductal adenocarcinoma of the prostate.

Ductal adenocarcinoma of the prostate (DAC) is considered to be an aggressive subtype of prostate cancer with greater risk of progression than acinar adenocarcinoma (AC). It has been debated whether DAC is a distinct subtype or a morphological variant of AC. Our aim was to examine the protein expression of DAC and to compare the results with AC. A tissue microarray was constructed from 60 DAC and 46 AC matched by Gleason score. The slides were stained for 28 immunomarkers (estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, PAX-2, and PAX-8). HMWCK was positive in 8.5 % of DAC, but negative in all cases of AC (p = 0.045). p16 was positive in 53.3 % of DAC and in 26.1 % of AC (p = 0.005). p53 was positive in 42.4 % of DAC and 26.7 % of AC (p = 0.031). A distinct patchy positivity of CK20 was seen in 23.7 % of DAC, and this pattern was also seen in 9.1 % of AC (p = 0.047). Villin was positive in 3.4 % of DAC while expression was negative in AC. Ki-67 labeling index was significantly higher in DAC than in AC (mean 9.2 % [95 % CI 6.4-12.0] and 2.6 % [1.9-3.4], p < 0.001). While there is some overlap in the immunohistochemical expression of DAC and AC, the differences between these two morphotypes of prostatic carcinoma are consistent with DAC having a more aggressive phenotype than AC.

Diagnostic criteria for ductal adenocarcinoma of the prostate: interobserver variability among 20 expert uropathologists.

AIMS: Ductal adenocarcinoma of the prostate (DAC) is clinically important, because its behaviour may differ from that of acinar adenocarcinoma. Our aims were to investigate the interobserver variability of this diagnosis among experts in uropathology and to define diagnostic criteria. METHODS AND RESULTS: Photomicrographs of 21 carcinomas with ductal features were distributed among 20 genitourinary pathologists from eight countries. DAC was diagnosed by 18 observers (mean 13.2 cases, range 6-19). In 11 (52%) cases, a 2/3 consensus was reached for a diagnosis of DAC, and in five (24%) there was consensus against. In DAC, the respondents reported papillary architecture (86%), stratification of nuclei (82%), high-grade nuclear features (54%), tall columnar epithelium (53%), elongated nuclei (52%), cribriform architecture (40%), and necrosis (7%). The most important diagnostic feature reported for DAC was papillary architecture (59%), whereas nuclear and cellular features were considered to be most important in only 2-11% of cases. The most common differential diagnoses were intraductal prostate cancer (52%), high-grade PIN (37%), and acinar adenocarcinoma (17%). The most common reason for not diagnosing DAC was lack of typical architecture (33%). CONCLUSIONS: Papillary architecture was the most useful diagnostic feature of DAC, and nuclear and cellular features were considered to be less important.

SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer.

UNLABELLED: Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison with benign tissue. In contrast, however, castration-resistant bone metastases exhibit reduced levels of SOCS2 in comparison with localized or hormone naive, untreated metastatic tumors. In PCa cells, SOCS2 expression is induced by androgens through a mechanism that requires signal transducer and activator of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response to GH. Our results suggest that the use of GH-signaling inhibitors could be of value as a complementary treatment for castration-resistant PCa. SUMMARY: Androgen induced SOCS2 ubiquitin ligase expression and inhibited GH signaling as well as cell proliferation and invasion in PCa, whereas reduced SOCS2 was present in castration-resistant cases. GH-signaling inhibitors might be a complementary therapeutic option for advanced PCa.

Histopathological features of ductal adenocarcinoma of the prostate in 1,051 radical prostatectomy specimens.

Ductal adenocarcinoma (DAC) of the prostate is thought to have worse prognosis than prostatic acinar carcinoma (PAC). We aimed to evaluate the prognostic significance of histopathological patterns of DAC. A series of 1,051 radical prostatectomy specimens from Karolinska University Hospital 1998-2005 was reviewed. A ductal component was classified as classical DAC (DACC) if it had columnar, pseudostratified epithelium, elongated nuclei, and papillary, glandular, or cribriform architecture; borderline DAC (DACB) if it lacked elongated nuclei or classical architecture; and prostatic adenocarcinoma with ductal features (PCDF) if stratified high-grade nuclei were found. DACC, DACB, and PCDF were seen in 2.6, 4.0, and 1.6 % of the cases. DAC was usually mixed with PAC and constituted 10-100 % (mean 40 %) of the main tumor. Location was periurethral, peripheral, or both in 69.8, 3.5, and 26.7 %. Necrosis was seen in 31.3 %, stromal invasion of DAC in 52.3 %, and intraductal spread in 91.9 %. In DACC/DACB and PAC, extraprostatic extension was seen in 66.7 and 42.4 % (p < 0.001) and seminal vesicle invasion in 13.0 and 5.0 % (p = 0.0045). DACC, DACB, and PCDF had a hazard ratio for biochemical recurrence of 1.5 (0.7-2.8), 1.4 (0.8-2.6) and 1.2 (0.5-2.7). When PCDF was excluded from DAC, hazard ratio was 1.4 (95 % CI 0.9-2.3, p = 0.12). Location, % DAC, necrosis, stromal invasion, or Gleason score were not predictive of recurrence. This suggests that DACC and DACB are more aggressive than average PAC, while cancers with acinar architecture and pseudostratified high-grade nuclei should not be included in DAC.