Sarcomatous Component Research Articles

Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.

Malignant mixed Müllerian tumor: Analysis of 21 cases at tertiary care rural hospital

Introduction: Malignant mixed Müllerian tumor (MMMT)/carcinosarcoma is an exceptionally rare tumor, representing just 1%–5% of all gynecological malignancies, but leading to 15% of gynecological malignancy-related deaths, with an occurrence of <2/1,00,000 women/year. Material and Methods: Twenty-one patients with MMMT of the uterus accounting for 1.7% of total uterine malignancies were included in the study. The histologic subtypes of the carcinoma and sarcoma components were examined and recorded. The proportions of carcinoma and sarcoma components were semi-quantitatively evaluated and recorded within the primary tumor site in the hysterectomy specimen. Among the metastatic sites and recurrent tumors, the histologic component (carcinoma vs. sarcoma) was evaluated. Results: Of these 21 cases, the carcinomatous component was further subtyped as 11 cases with endometrioid morphology, four cases each of clear cell and serous morphology, and two cases had undifferentiated epithelial component. Most of the tumors had carcinomatous components and 55% of tumors were high grade. Prognostic factors include the presence of bleeding (P = 0.05) which is associated with poor outcomes. Other known prognostic factors like myometrial invasion (P = 0.46) and stage of disease (P = 0.86) did not show any prognostic significance in present study. Conclusions: The elderly age, higher stage, and a poorly differentiated tumor are associated with poor outcomes. Utmost efforts should be made to educate women in early cancer detection by creating awareness on risk factors and symptoms. Study on the trends of gynecological cancers is essential to plan and evaluate cancer control programs.

Prognostic Factors of Gliosarcoma in the Real World: A Retrospective Cohort Study.

Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma. By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2013 to 2021 were identified. Clinical, pathological, and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using the Cox proportional hazards model with backward stepwise regression analysis. Forty-five GSM patients were included. Median overall survival was 25.6 months (95% CI 8.0-43.1), and median relapse-free survival was 15.2 months (95% CI 9.7-20.8). In multivariable analysis, total resection (p = 0.023, HR = 0.192, 95% CI 0.046-0.797) indicated an improved prognosis. And low expression of Ki-67 (p = 0.059, HR = 2.803, 95% CI 0.963-8.162) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy with concurrent temozolomide (n = 33, 73.3%, log-rank p = 0.99) or adjuvant temozolomide (n = 32, 71.1%, log-rank p = 0.74). This single-center retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 which are beneficial for patients with GSM, while radiotherapy or temozolomide is not.

Prognostic significance of heterologous component in carcinosarcoma of the gynecologic organs: a systematic review and meta-analysis.

The aim of this study is to determine the histologic presence of heterologous component as a prognostic factor in gynecologic carcinosarcoma through a systematic review and meta-analysis. PubMed, Web of Science, and Embase were searched for publications. Studies that evaluated survival effect of sarcomatous component based on histology in human ovarian or uterine carcinosarcoma were included. Two authors independently reviewed the references based on eligibility criteria and extracted the data including primary tumor site, survival outcome, type of survival outcome, and proportion of each sarcomatous differentiation. The quality of each eligible study was assessed with Newcastle-Ottawa scale. Meta-analysis was conducted using a random-effects model to estimate hazard ratio (HR) and 95% confidence intervals (CIs) of survival outcome for carcinosarcoma with or without heterologous component. Eight studies including 1,594 patients were identified. Overall proportion of carcinosarcoma with heterologous component was 43.3%. Presence of heterologous component was associated with worse overall survival (HR=1.81; 95% CI=1.15-2.85) but not with pooled recurrence-free survival and disease-free survival (HR=1.79; 95% CI=0.85-3.77). Removing multivariate analysis studies, early-stage studies, ovarian tumor study, or studies with large number of patient samples did not affect the significance between heterologous component and overall survival. Gynecologic carcinosarcoma is histologically a biphasic tumor which comprise of epithelial and mesenchymal components. Our study emphasizes pathologic evaluation of heterologous component as a prognostic factor in gynecologic carcinosarcoma when all stages were considered. PROSPERO Identifier: CRD42022298871.

The prognostic significance of the heterologous component in uterine carcinosarcomas.

Uterine carcinosarcomas are aggressive, rare biphasic tumors with malignant epithelial and malignant sarcomatous components. The prognostic significance of the presence of extrauterine sarcoma (heterologous component) is controversial. Therefore, the aim of this study was to investigate the effect of heterologous components in uterine carcinosarcomas on disease-free survival, overall survival, and other prognostic factors. Clinical and histopathological data from patients treated for uterine carcinosarcoma in a tertiary cancer center in Turkey between July 2000 and January 2020 were collected. Independent risk factors affecting overall survival and disease-free survival were analyzed by univariate and multivariate Cox regression analyses. A total of 98 patients were identified. The median follow-up was 21.8 (1.2-233.1) months. In the multivariate analysis, the median overall survival and disease-free survival were 23.8 and 20.7 months in those with homologous mesenchymal components and 17.6 and 9.7 months in those with heterologous mesenchymal components, respectively. It was found that the presence of heterologous mesenchymal components significantly reduced both overall survival and disease-free survival (odds ratio [OR], 2.861; 95% confidence interval [CI] 1.196-6.841; p=0.018 and OR, 3.697; 95%CI 1.572-8.695; p=0.003, respectively). In addition, both lymphadenectomy and adjuvant radiotherapy were found to significantly increase overall survival and disease-free survival. Age was found to increase only disease-free survival. The results obtained in this study showed that the presence of heterologous components in uterine carcinosarcoma is a prognostic factor that adversely affects both overall survival and disease-free survival. Lymphadenectomy and adjuvant radiotherapy have beneficial effects on both overall survival and disease-free survival.

Dedifferentiated chordoma: A rare tumor with diagnostic challenge

Chordomas are rare locally invasive malignant bone tumors arising from remnants of embryonic notochord. Dedifferentiated chordoma (DC), a rare subtype, is characterized by the presence of a sarcomatous component in conventional chordoma (CC) which may arise de novo or as a malignant transformation of previously treated chordoma. The presence of dedifferentiation warrants a poor prognosis due to distant metastasis and recurrences. De novo DCs pose a diagnostic challenge especially in small biopsies and at metastatic sites. Here, we report the case of a 45-year-old female presenting with a long history of backache and constipation, finally diagnosed as DC. Radiological as well as histomorphological pictures of the tumor posed diagnostic challenges because they can mimic other tumors occurring in a similar location. We found this case worth reporting as de novo DC is rarely reported in the literature and it has the potential to pose diagnostic as well as therapeutic challenges. Here we report a case of dedifferentiated chordoma presenting with diagnostic challenge both radiologically and histomorphologically and discuss the role of immunohistochemistry.

The worst of both worlds - carcinosarcoma of the ovary: A case report

Ovarian carcinosarcoma (OCS) is a rare, highly aggressive neoplasm characterized by presence of both carcinomatous and sarcomatous component. Even after evolution of chemotherapy with introduction of platinum agents, the survival still seems to be poor. A report of such rare case tumour in a 62 year old female is presented here.

Case report: carcinosarcoma of the fallopian tube

Abstract Introduction/Objective Carcinosarcoma is a malignant biphasic tumor composed of carcinomatous and sarcomatous elements. Carcinosarcoma of the fallopian tube is an extremely rare malignancy with fewer than 100 cases reported in the literature. We report a rare case of carcinosarcoma arising from the right fallopian tube. Methods/Case Report A 72-year-old female presented with worsening vaginal discharge and abdominal cramps. Abdominal computed tomography detected a right adnexal mass. A torsed fallopian tube with a large mass was identified intraoperatively. Grossly, a 3.1 cm tan friable mass was seen protruding from the right fallopian tube lumen with numerous detached tumor fragments (9.4 cm in aggregate). Microscopically, the tumor was biphasic with a major mesenchymal component and minor epithelial component. A solid pattern of spindled and epithelioid cells with heterologous element of chondrosarcoma and a separate component with features of high-grade serous carcinoma in cribriform and solid sheets with slit-like spaces were seen. Both components showed marked nuclear atypia, pleomorphism, prominent nucleoli, and frequent mitoses. Both components were positive for p53, PAX-8, and beta- catenin immunohistochemistry, with a Ki-67 index of 80-90%. The sarcoma component was positive for p16, vimentin, and smooth muscle actin; the carcinoma component was positive for WT1, pan-cytokeratin, and cytokeratin 7. Pelvic washings were negative for malignancy. Metastases were not identified. Chemotherapy with paclitaxel and carboplatin was initiated with no recurrence identified 17 months after treatment. Results (if a Case Study enter NA) N/A Conclusion Proper identification and reporting of rare malignancies, such as this fallopian tube carcinosarcoma, with treatment and follow up, provide oncologists with the necessary information to advance treatment.

Primary Hepatic Carcinosarcoma: A Rare Diagnosis With Unique Morphology

Abstract Introduction/Objective The terminology and pathogenesis of primary hepatic carcinosarcoma remain controversial, as they are less than 1% of all hepatic cancers. The diagnostic challenges include interpreting their distinct morphology, immunohistochemical staining and excluding the differential diagnosis. Methods/Case Report Our case is of a 72-year-old man with history of smoking and occasional alcohol use. There was no history of viral hepatitis. He came with the complaint of abdominal pain and found to have 20 cm confluent mass in the left lobe of liver on imaging studies. Needle core biopsy was performed on the liver mass and showed biphasic malignant neoplasm with geographic necrosis. The tumor displayed two distinct patterns of growth. Portions of tumor exhibit vesicular nuclei with prominent nucleoli and abundant granular cytoplasm forming sheets and pseudoglandular structures. There were also separate well-demarcated foci of undifferentiated malignant epithelioid to spindle cells with abundant mitosis and apoptosis. The areas of hepatocellular differentiation were positive for Hep- Par-1, arginase and cytokeratin cam 5.2 and weak staining for glypican-3. They were negative for vimentin and smooth muscle actin. In contrast, the undifferentiated component is negative for Hep-Par-1, arginase, cytokeratin cam 5.2 and positive for vimentin (but not smooth muscle actin). The morphology and immunohistochemical staining pattern were consistent with a hepatic carcinosarcoma with undifferentiated sarcomatous component. The patient was put on palliative care due to the advanced nature of his disease. Results (if a Case Study enter NA) NA. Conclusion Despite the advancements in diagnostic techniques and treatment modalities, hepatic carcinosarcoma still is a rare occurrence with very dismal prognosis.

A case of undifferentiated carcinoma of the bladder treated by combination therapy of surgery, local radiation, and immune checkpoint inhibitors.

Undifferentiated carcinoma of the bladder is a rare malignancy with a poor prognosis. We present the case of an 81-year-old woman complaining of bladder irritation. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a bulky bladder tumor, which was diagnosed as cT4aN0M0. A transurethral resection of the bladder tumor revealed pT2 or higher urothelial carcinoma. The patient underwent total cystectomy with an ileal conduit diversion. Histological examination revealed a primary undifferentiated bladder carcinoma with a sarcoma component, pT3aN0M0. Postoperative adjuvant chemotherapy with gemcitabine plus carboplatin was administered. However, this regimen was discontinued after one course due to significant myelosuppression. Four months after total cystectomy, a pelvic tumor with suspected local recurrence was detected on CT. The patient was diagnosed with recurrent undifferentiated carcinoma with a sarcoma component by a transperineal ultrasound-guided biopsy. Local radiation therapy and immunotherapy with immune checkpoint inhibitors were prescribed. After three courses of immunotherapy with pembrolizumab, the primary tumor disappeared. Upon continuing immune checkpoint inhibitor treatment, the patient has maintained a complete response without tumor recurrence in the following six months.

Computed Tomography, Magnetic Resonance Imaging, and Pathological Features of Gliosarcoma.

To investigate the clinical, imaging, and pathological features of gliosarcoma. The clinical data of 14 patients with gliosarcoma confirmed by surgery and pathology at our hospital between 2010 and 2021 were analyzed retrospectively, and the relevant literature was reviewed. In all 14 cases, the gliosarcoma was located in the supratentorial brain parenchyma and involved a single lesion. There were more male patients (64.3%) than female patients (35.7%), and 57.1% of all the patients were 40-60 years of age. The prognosis of all 14 patients was poor, and the average survival time was approximately seven months. The computed tomography findings revealed mostly mixed density lesions, and some cases were complicated with bleeding. The magnetic resonance imaging revealed irregularly shaped mass lesions of different sizes, with uneven or circular enhancement. Cystic degeneration and necrosis could be seen in all the masses, some of which showed signs of bleeding and were surrounded by different degrees of edema and space-occupying effects. The pathological examination revealed that the tumors had bidirectional differentiation of the glial and sarcoma components, while the immunohistochemistry examination revealed glial fibrillary acidic protein-positive and reticular fiber-positive staining in the sarcoma. The clinical manifestations of gliosarcoma are nonspecific, but imaging reveals that the condition has certain characteristics, typically consisting of a huge supratentorial mass, with an irregular heterogeneous periphery or obvious mass-like augmentation after enhancement. The final diagnosis depends on the results of a pathological examination.

Clinical features and prognostic factors of pulmonary carcinosarcoma: A nomogram development and validation based on surveillance epidemiology and end results database.

Pulmonary carcinosarcoma (PCS) is a rare but aggressive malignant disease in the lung. It is characterized by coexisting histologic elements of carcinomatous and sarcomatous components. This study aimed to comprehensively understand the clinical features of PCS and develop a nomogram for prognostic prediction of PCS patients. Data were collected from the Surveillance Epidemiology and End Results (SEER) database between 1975 and 2018. Propensity-score matching (PSM) was used to match the demographic characteristic of the PCS vs. pulmonary sarcoma (PS). Cancer-specific survival (CSS) and overall survival (OS) were the main endpoints of the survival of patients and were evaluated using the Kaplan Meier curves and Cox proportional hazards regression. We further randomly split enrolled PCS patients from SEER into the training and validation sets. All independent predictors for OS of the training set were integrated to create a predictive nomogram. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability both in the training and validation cohorts. In addition, the clinical data of PCS patients from the West China Hospital were also retrospectively analyzed by this model. A total of 428 PCS patients and 249 PS patients were enrolled from SEER. Compared to pure PS, PCS was associated with significantly better survival in the unmatched cohorts, whereas non-significantly better survival after PSM. In subgroup analysis, PCS showed significantly worse survival than pure PS in subgroups among the race, marital status, and radiation treatment. A nomogram was constructed for PCS patients' survival prediction by combining the independent risk factors, including gender, stage, surgery, radiation, and chemotherapy. The nomogram showed good discrimination, calibration, and predictive power in the training and validation sets. Risk stratification analysis indicated that the nomogram scores efficiently divided PCS patients into low and high-risk groups. PCS is a rare malignant disease of the lung with distinct clinical features. It had a comparable survival compared with pure PS in the matched cohorts. In addition, a nomogram was developed and validated for predicting the OS in PCS patients.

Inter-component immunohistochemical assessment of proliferative markers in uterine carcinosarcoma.

In the scientific literature, a selected number of reports have investigated the impact of proliferative activity on the development and progression of uterine carcinosarcomas (UC). The aim of the present retrospective study was to compare the immunohistochemical proliferation markers [Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 3 (MCM3), and topoisomerase IIα (topoIIα)] assessment in both components of UC. A total of 30 paraffin-embedded slides of UCs, obtained from patients who underwent surgery between January 1, 2006, and December 31, 2020, were analyzed. Medical records and clinicopathological data of patients were reviewed. Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki67, PCNA, MCM3 and topoIIα. Ki67-positive nuclear immunoreactivity was reported in 20 (67%) and 16 (53%) UC carcinomatous and sarcomatous components, respectively. In the epithelial component, Ki67 positive staining was related to the International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.025), and histological grade (G1 vs. G2/G3, P=0.031). Nuclear PCNA reactivity was observed in 18 (60%) and 16 (53%) carcinomatous and sarcomatous components, respectively. Notably, all four cases with omental metastases were PCNA-positive, and a relationship between staining pattern and the existence of metastases was of significant value (P=0.018). MCM3-positive nuclear staining was found nearly twice as high in the carcinomatous (n=19; 63%), compared with the sarcomatous (n=11; 37%) component, respectively, and MCM3 expression in the epithelial component was related to clinical stage (P=0.030), and the existence of omental metastasis (P=0.012). In addition, out of the 30 UCs, 17 (57%) and 13 (43%) showed topoIIα positivity in the carcinomatous and sarcomatous UC components, respectively. A significant relationship between protein immunoreactivity and FIGO stage (P=0.049), and omental metastasis (P=0.026) was revealed to exist. However, no significant differences between expression of proliferation markers and clinicopathological features in the sarcomatous UC component were identified. Finally, a significant correlation between each protein immunohistochemical staining was demonstrated, particularly in the sarcomatous UC component. Collectively, a combined analysis of Ki67, PCNA, MCM3, and topoIIα may provide more detailed information of cell-cycle alterations determining the heterogeneity of uterine carcinosarcomas.

Multicenter observational study on optimal regimen of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, and peritoneal cancer (328)

Multicenter observational study on optimal regimen of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian tube, and peritoneal cancer (328)

Gastric carcinosarcoma with FGFR2 amplification under long-term control with pazopanib: a case report and literature review

BackgroundGastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib.Case presentationA 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor–node–metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months.ConclusionsWe report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

Management of a rare ovarian carcinosarcoma: A case report and literature review.

Ovarian carcinosarcoma (OCS) is a rare and lethal gynecological cancer. The present study reports on the case of a 61-year-old post-menopausal female with abdominal distension who was detected to have a large OCS. The patient underwent cytoreductive surgery, including sub-extensive hysterectomy, bilateral adnexectomy, sigmoid colon and partial rectal resection, and lymph node dissection. Postoperative pathology of the bilateral adnexal masses revealed carcinosarcoma. The main components of the carcinoma included serous carcinoma and a small amount of squamous cell carcinoma. The sarcoma components mainly contained fibrosarcoma, as well as a small amount of chondrosarcoma and rhabdomyosarcoma. Infiltrating cells in cancer tissues or metastasis were observed in the serosal surface, muscular and subserosal layers of the uterus, as well as the sigmoid colon and part of the rectum. The patient was diagnosed postoperatively with International Federation of Gynecology and Obstetrics stage IIIC ovarian carcinosarcoma and T3cN1M0 based on the TNM system. The patient then received six cycles of combination chemotherapy using carboplatin, paclitaxel plus bevacizumab. As severe myelosuppression occurred during and after chemotherapy, and bevacizumab was expensive, bevacizumab therapy was not maintained after chemotherapy. However, following chemotherapy, the patient received niraparib oral maintenance therapy. At 6 months after the sixth chemotherapy, cancer antigen 125 levels dropped to 4.55 U/ml (within normal range). Short-term follow-up of 6 months after the end of chemotherapy indicated that the patient had a remission prognosis based on the ultrasonography, computed tomography, magnetic resonance imaging examinations and serum tumor marker levels. The present study indicated that combined chemotherapy and targeted therapy after cytoreductive surgery may be a promising way for the treatment of OCS.

Molecular and expressional characterization of tumor heterogeneity in pulmonary carcinosarcoma.

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.

Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS-mutant neurocutaneous melanosis.

Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS-mutant neurocutaneous melanosis.

Histopathologic features and molecular genetic landscape of HER2-amplified endometrial carcinomas

AbstractHER2 is an established therapeutic biomarker in advanced or recurrent endometrial serous carcinoma. Current clinical guidelines recommend HER2 testing exclusively in this endometrial carcinoma (EC) subtype; however, the full spectrum of ECs harboring HER2 amplification remains ill-defined. The present study characterizes the clinicopathologic and molecular features of HER2-amplified ECs across all histologic subtypes. Retrospective analysis of our institutional cohort of 2,042 ECs subjected to targeted clinical massively parallel sequencing identified 77 (3.8%) cases with HER2 amplification, a group comprised of serous (n = 29), endometrioid (low-grade, n = 2, high-grade, n = 1) and clear cell (n = 4) carcinomas, carcinosarcomas (n = 18) and high-grade ECs with ambiguous features (HGEC, n = 23). A co-existing TP53 mutation was identified in 94% (72/77) of HER2-amplified ECs. Other recurrent genetic alterations included amplification of CCNE1 (22%) and ERBB3 (10%), FBXW7 mutations or deletions (13%), and mutations in PIK3CA (40%) and PPP2R1A (13%). The HER2 immunohistochemistry score was 2+ or 3+ for all evaluable cases (n = 61). Apart from carcinosarcomas, which often showed lower HER2 expression, particularly in the sarcomatous component, HER2 immunohistochemical staining pattern and intensity were similar across EC subtypes. Intratumor heterogeneity in HER2 expression was common and correlated with genetic heterogeneity as detected by fluorescence in-situ hybridization. These results demonstrate the frequent co-occurrence of HER2 amplification with TP53 mutation and high-grade histology, rather than being specific to serous carcinoma, per se. Overall, these findings suggest that HER2 targeted therapy may be more broadly applicable to all high-grade EC histotypes and consideration should be given to expanding therapeutic eligibility.

Cytologic presentation and clinicopathologic correlation of Mullerian carcinosarcoma on serous fluid samples.

Limited data are present to study the cytologic findings of Mullerian carcinosarcoma (MCS) in serous fluid samples and clinicopathologic features that are associated with cytology yield. We studied 30 MCS patients diagnosed on surgical resection samples, and reviewed their cytomorphology and immunophenotypes on concurrent serous fluid cytology samples. Clinicopathologic features were also compared between cases with positive or negative cytology. Fourteen out of 30 patients showed positive cytology, including 12 patients with only carcinomatous components and 2 with sarcomatous cells. Cytomorphology of MCS was mostly consistent with adenocarcinoma, with psammoma bodies occasionally present. The 2 cases with sarcomatous cells showed spindle cells without signs of heterologous differentiation. PAX8 was positive in 10 of 11 cases, and WT1 was positive in 8 of 11 cases including the case with negative PAX8. In 1 case, PAX8 and WT1 were only positive in the sarcomatous but not in carcinomatous cells. MOC31 showed consistent positivity in carcinomatous cells, which appeared to be more sensitive than B72.3 (positive in 72.7%). In addition, sarcomatous cells showed CD10 positivity in 1 case. Clinically, patients who developed body cavity effusions or with higher stage diseases were more likely to have positive cytology. Cytologic diagnosis of MCS in the serous fluid is challenging due to the rare presence of sarcomatous component. Staining both PAX8 and WT1 is recommended to confirm their Mullerian origin, although both markers may be positive only in sarcomatous cells. Cytology yield of MCS is highly associated with the disease stage.