Adamantinoma-like Ewing sarcoma typically shows t(11;22) EWSR1::FLI1 translocation and complex epithelial differentiation. It poses a diagnostic challenge, especially in the head and neck region, due to its under-recognition and significant histologic overlap with other malignancies. Neoadjuvant and adjuvant treatment information on head and neck Adamantinoma-like Ewing sarcoma is limited. Herein, we report a case of a 78-year-old female with Adamantinoma-like Ewing sarcoma of the parotid gland, including the imaging findings and clinical response to neoadjuvant therapy followed by surgery. The efficacy of neoadjuvant therapy in the treatment of Adamantinoma-like Ewing sarcoma is discussed in the context of a review of pertinent literature. Adamantinoma-like Ewing sarcoma in the head and neck is frequently misdiagnosed as poorly differentiated squamous cell carcinoma or a basaloid salivary gland carcinoma. Adamantinoma-like Ewing sarcoma is a EWS1::FLI1 translocation driven tumor; frequently misdiagnosed on head and neck biopsies as poorly differentiated carcinoma, or squamous cell carcinoma. Ewing sarcoma-specific chemoregimen appears effective for this entity. If diagnosed early, patient may be amenable to neoadjuvant therapy, which may improve surgical and cosmetic outcomes. This is especially important in head and neck regions.

Treatment for endometrial cancer is rapidly evolving with the increased use and integration of somatic tumor RNA sequencing in clinical practice. There is a paucity of data regarding PARP inhibition in endometrial cancer given that mutations in homologous recombination genes are rare, and currently no FDA approval exists. A 50-year-old gravida 1 para 1 woman with a diagnosis of stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented to our comprehensive cancer center. Following surgical staging, she was placed on adjuvant chemotherapy with carboplatin/paclitaxel which was held multiple times due to poor performance status and complications. CT scan of the abdomen and pelvis following cycles 3 of adjuvant chemotherapy showed recurrent progressive disease. She received one cycle of liposomal doxorubicin but discontinued it due to severe cutaneous toxicity. Based on the BRIP1 mutation identified, the patient was placed on compassionate use of Olaparib in January 2020. Imaging during this surveillance period showed a significant decrease in hepatic, peritoneal, and extraperitoneal metastases, and eventually the patient had a clinical complete response in a year. The most recent CT A/P in December 2022 showed no sites of active recurrent or metastatic disease in the abdomen or pelvis. We present a unique case of a patient with recurrent stage IVB poorly differentiated endometrioid endometrial adenocarcinoma with multiple somatic gene mutations including BRIP1, who had a pathologic complete response following compassionate use of Olaparib for 3 years. To our knowledge, this is the first reported case of high grade endometrioid endometrial cancer that has shown a pathologic complete response to a PARP inhibitor.

Epithelial ovarian cancer (EOC) is the most common histology of ovarian cancer defined as epithelial cancer derived from the ovaries, fallopian tubes, or primary peritoneum. It is the fifth most common cause of cancer-related death in women in the United States. Because of a lack of effective screening and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer consists of a combination of cytoreductive surgery and systemic chemotherapy. Despite the advances with new cytotoxic and targeted therapies, the five-year survival rate for all-stage EOC in the United States is 48.6%. Delivery of up-to-date guideline care and multidisciplinary team efforts are important drivers of overall survival. In this paper, we review our frontline management of EOC that relies on a multi-disciplinary approach drawing on clinical expertise and collaboration combined with community practice and cutting edge clinical and translational research. By optimizing partnerships through team medicine and clinical research, we combine our cancer center clinical expertise, community practice partnership, and clinical and translational research to understand the biology of this deadly disease, advance therapy and connect our patients with the optimal treatment that offers the best possible outcomes.

Background: Distinction of idiopathic pulmonary fibrosis (IPF) from other chronic fibrosing interstitial pneumonitides, such as hypersensitivity pneumonitis (HP) and connective tissue diseases, is critical due to varied biological and clinical outcomes. However, their histologic overlaps often pose diagnostic challenges. A recent study suggested an association of herpesvirus saimiri infection with IPF. Productive viral infection is associated with coexpression of pirated mammalian protein cyclin D1, shown to be overexpressed by immunohistochemistry (IHC) in the regenerating alveolar epithelium in IPF but not in normal lungs. We evaluated the diagnostic utility of cyclin D1 to discriminate between IPF and other fibrosing interstitial lung diseases. Materials and Methods: A retrospective study of cyclin D1 IHC expression in 27 consecutive cases of chronic fibrosing interstitial lung diseases from 2011 to 2017: 12 usual interstitial pneumonia (UIP) pattern; 5 nonspecific interstitial pneumonia pattern; 3 HP pattern; 7 unclassifiable was performed. Five cases of normal lung obtained from lobectomy specimen for malignancy are included as control. Immunoreactivity was graded semiquantitatively on a scale of 0 to 3. Results: Cyclin D1 staining was uniformly strongly positive in all cases evaluated in the study, particularly in proliferating type II pneumocytes in the region of fibrosing areas. There was no statistical difference in the extent of cyclin D1 expression between UIP and non-UIP groups (2.7 vs. 2.5) and IPF versus non-IPF groups (2.7 vs. 2.4). Cyclin D1 expression is lower in control group compared with UIP groups (1.2 vs. 2.7). Conclusions: Cyclin D1 is not a specific marker of UIP pattern/IPF. The high expression of cyclin D1 in lung tissue of fibrosing interstitial pneumonitides regardless of etiology most likely correlates with proliferation in type II pneumocytes.

SMARCA4 gene encodes BRG1 , a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular processes. In the uterine corpus, SMARCA4 / BRG1 deficiency is associated with a novel class of undifferentiated uterine sarcomas, characterized by younger age onset, rhabdoid histology, focal phyllodiform architecture, high-risk pathologic findings, and dismal prognosis. Herein, we report a case of a 34-year-old Asian woman with a SMARCA4 / BRG1 -deficient uterine tumor fulfilling the clinicopathologic features of an undifferentiated uterine sarcoma. However, the tumor exhibited several unique features that have not been previously emphasized, including (1) conspicuous phyllodiform architecture recapitulating conventional adenosarcoma, (2) rhabdoid tumor cells forming cords and keratin-positive cohesive epithelial islands, and (3) cooccurrence with a spatially distinct and discrete endometrial complex atypical hyperplasia from the rest of the proliferation. By immunohistochemistry, the tumor cells were diffusely positive for synaptophysin, whereas BRG1 was lost. Pertinent molecular findings included frameshift mutations in the SMARCA4 gene, mutations in histone modification and chromatin remodeling genes, including KMT2C , ARID1B , KAT6A , and NCOR1 , and mutations in Wnt signaling involving APC and CTNNB1 . Copy number gain in MDM2 and CDK4 were also identified. The tumor mutation burden was intermediate (6.8/MB) and it was microsatellite stable. On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4 / BRG1 -deficient uterine neoplasms.

Histologic and genetic mutation information from racially and ethnically diverse populations is warranted to better inform future cancer predisposition and promote health equity. A single institutional, retrospective capture of patients with gynecologic conditions and genetic susceptibilities to malignant neoplasms of the breast or ovaries was performed. This was achieved with manual curation of the electronic medical record (EMR) from 2010–2020 with the use of ICD-10 code searches. Among 8983 consecutive women identified with gynecologic conditions, 184 were diagnosed with pathogenic/likely pathogenic (P/LP) germline BRCA (gBRCA) mutations. Median age was 54 (22–90). Mutations included insertion/deletion (majority frameshift, 57.4%), substitution (32.4%), large structural rearrangement (5.4%), and alteration in splice site/intronic sequence (4.7%). A total of 48% were non-Hispanic White, 32% Hispanic or Latino, 13% Asian, 2% Black, and 5% Other. The most common pathology was high grade serous carcinoma (HGSC, 63%), followed by unclassified/high grade carcinoma (13%). Additional multigene panels led to the detection of 23 additional BRCA-positive patients with germline co-mutations and/or variants of uncertain significance in genes functionally involved in DNA repair mechanisms. Hispanic or Latino and Asian individuals comprised 45% of patients with concomitant gynecologic condition and gBRCA positivity in our cohort, confirming that germline mutations are represented across racial and ethnic groups. Insertion/deletion mutations, the majority of which led to a frameshift change, occurred in approximately half of our patient cohort, which may have prognostic implication for therapy resistance. Prospective studies are needed to unravel the significance of germline co-mutations in gynecologic patients.