Comprehensive characterization of genomic features and clinical outcomes following targeted therapy and secondary cytoreductive surgery in OCCC: a single center experience.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). METHODS: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. RESULTS: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progression-free survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0-16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. CONCLUSION: Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Amyloid and hyaline globules in undifferentiated nasopharyngeal carcinoma.

We characterize the clinicopathological features of two patients (one 38 year old woman and one 42 year old man, both of Chinese ethnicity) with Epstein Barr Virus positive non-keratinizing nasopharyngeal carcinoma from an endemic region with prominent presence of amyloid and one case with both amyloid and abundant intracytoplasmic hyaline globules. The amyloid material was positive for Congo red and showed apple green birefringence when examined under polarized light. The amyloid was immunoreactive for cytokeratins and was located both intra- and extracellularly. Frequently the amyloid had a light microscopical spherical appearance and displayed peripheral radiating fibrils from a central homogenous core. One of the patients had a unique presentation of nasopharyngeal carcinoma with perceived hemoptysis and coughing up two pieces of tumor tissue. In reality, the nasopharyngeal tumor was polypoid and the two fragments were pinched of from the main tumor mass.

Primary Adrenal Angiomatoid Fibrous Histiocytoma With Novel EWSR1-ATF1 Gene Fusion Exon-Exon Breakpoint.

We describe the clinical, pathological, and molecular features of a primary adrenal angiomatoid fibrous histiocytoma (AFH) in an 11-year-old girl presenting with pyrexia of unknown origin. We performed next-generation sequencing-based anchored multiplex polymerase chain reaction (Archer® FusionPlex® sarcoma assay), which revealed an EWSR1-ATF1 gene fusion with novel breakpoints in exon 11 of EWSR1 and exon 3 of ATF1. The pyrexia resolved fully after surgical resection, and the patient was disease-free on follow-up at 1 year and 6 months. This case exemplifies the value of molecular testing of pediatric neoplasms presenting at unusual sites for diagnosis and identification of novel gene fusion breakpoints.

Solitary vertebral metastasis of primary clear cell carcinoma of the liver: a case report and review of literature.

Primary clear cell carcinoma of liver (PCCCL) is an uncommon variant of primary hepatocellular carcinoma. Though the literature describes a better prognosis in relation to the proportion of clear cells in the tumour when compared to the other variants, there is no general consensus in the management due to its rarity and unclear clinicopathological and prognostic factors. There is dearth of evidence with regard to the metastasizing nature of PCCCL and its management. In addition, the management of recurrent spinal tumours both primary and metastatic is not clear as the available evidence is mostly based on case reports. We describe an unusual presentation of PCCCL with solitary spinal metastasis and further complicated by tumour recurrence in a 71-year-old male. Such presentation has never been described before. He presented with low back pain and incomplete neurological deficits involving both lower limbs. On detailed evaluation, he was found to have a solitary metastasis at L3 vertebra secondary to PCCCL. He underwent radical excision of tumour and reconstruction for the solitary metastasis at L3 vertebral body and trans arterial chemo embolisation (TACE) for the hepatic lesion. Pt was asymptomatic until 9 months post operatively when he developed tumour recurrence at L3 vertebra. Patient subsequently underwent 2 stage palliative surgery followed by radiotherapy and chemotherapy. At his latest follow-up (1 year), the patient's overall general condition has improved with residual neurological deficits in the lower limb. PCCCL is a rare type of hepatocellular carcinoma which can present as "solitary metastasis" to the spine. Although the literature suggests a good prognosis for this histological type, this case did not have a good outcome. In addition to providing information for the management of similar cases in the future, this case report highlights that every patient has to be managed on a case-by-case basis.