Pancreatic Diffuse Large B-cell Lymphoma in the US Population.

BACKGROUND: Pancreatic lymphomas (PLs) represent <2% of all lymphomas and <0.5% of all pancreatic neoplasms. An accurate histologic diagnosis of PL is needed to predict prognosis and adequately treat the patient. This study aims to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of pancreatic diffuse large B-cell lymphoma (DLBCL). METHODS: Demographic and clinical data from 493 cases of DLBCL of the pancreas were identified between 2000 and 2018 using the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The most common age group was between the ages of 70 and 79 years (27.0%). While 44% of cases involved distant sites (a proxy for secondary pancreatic DLBCL), regional and localized involvement was seen in 33%, with the most common cause of death being a primary pancreatic DLBCL. Most patients (71%) received only chemotherapy (systemic therapy). The overall five-year observed survival was 46% (95% CI, 43.5-48.3). The one-year and five-year survival with chemotherapy only was 68% (95% CI, 65.3-70.3) and 48% (95% CI, 44.7-50.5), respectively. The one-year and five-year survival with surgery and chemotherapy was 96% (95% CI, 91.3-99.9) and 80% (95% CI, 71.4-89.2), respectively. Surgery with chemotherapy (HR: 0.397 (95% CI, 0.197-0.803), p = 0.010) were both positive predictors in survival prognosis. Multivariable analysis identified age >55 years (HR: 2.475 (95% CI, 1.770-3.461), p < 0.001), distant stage (HR: 6.894 (95% CI, 4.121-11.535), p < 0.001), and undergoing no surgery (HR: 2.610 (95% CI, 1.307-5.215), p = 0.007) as negative predictors for survival. CONCLUSION: PLs are rare malignant pancreatic neoplasms with DLBCL being the most common histological subtype. An accurate and timely diagnosis of pancreatic DLBCL is necessary to implement effective treatments and reduce mortality. Systemic therapy (chemotherapy) with or without surgical therapy improved survival. Increased age and regional and distant spread negatively impacted survival.

The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation.

(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).

Pleomorphic high grade endometrial stromal sarcoma with YWHAE gene amplification may be a novel variant with poor prognosis.

Endometrial stromal neoplasms are classified by the World Health Organization (WHO) into endometrial stromal nodule (ESN), low grade (LGESS), high grade (HGESS), and undifferentiated uterine sarcoma (UUS). HGESS is subclassified based on molecular findings, YWHAE or BCOR. The HGESS with YWHAE::NUTM2A/B (alias YWHAE::FAM22A/B) fusion usually have relatively monomorphic (as with most fusion-associated malignancies) rounded to epithelioid cells with eosinophilic cytoplasm, vesicular nuclei, nucleoli, and mitotic figures >10/10 HPF. We present a 66-year-old woman with post-menopausal bleeding found to have a heterogeneous solid-cystic uterine mass on CT who underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic lymph node dissection. A 15.0×9.0 cm variegated uterine mass with hemorrhage and necrosis was identified. Histologically, the tumor was hypercellular with haphazard fascicles, microcysts, and tongue-like destructive myometrial invasion. Tumor cells exhibited marked pleomorphism and high mitotic activity with atypical mitotic figures. There was extensive cyclin-D1 and subset CD10 immunopositivity. FISH showed YWHAE amplification but without rearrangement. Interestingly, we found only two other reported cases of pleomorphic HGESS with YWHAE gene amplification upon review of 259 cases from cBioPortal database, one of which was reported as carcinosarcoma with heterologous elements. Of note, all three YWHAE amplified cases were diagnosed at high-stage and succumbed to disease within six months. Our case appears to be the third case of YWHAE-amplified pleomorphic HGESS, possibly a new variant of uterine sarcoma with aggressive biologic behavior that needs further evaluation.

Parathyroid Carcinoma: Incidence, Survival Analysis, and Management: A Study from the SEER Database and Insights into Future Therapeutic Perspectives.

Introduction: Parathyroid carcinoma (PC) is an extremely rare entity, with a frequency of 0.005% of all malignancies. Most data related to this rare disease are limited to case series and a few database studies. We present a large database study that aims to investigate the demographic, clinical, and pathological factors, prognosis, and survival of PC. Methods: Data of parathyroid carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) diagnosed between 1975 and 2016. Results: PC had a slightly higher incidence in men (52.2%, p < 0.005), the majority of cases affected Caucasians (75.4%, p < 0.005), and the mean age at diagnosis was 62 years. Histologically, 99.7% were adenocarcinomas not otherwise specified (p < 0.005), well-differentiated (p < 0.005), and 2−4 cm (p < 0.001) in size among the patients with available data. In cases with staging provided, most PC were organ-confined (36.8%, p < 0.001). Lymph nodes were positive in 25.2% of cases where lymph node status was reported. The main treatment modality was surgery (97.2%), followed by radiation alone (2%), and very few received chemotherapy alone (0.8%), p < 0.005. Five-year follow-up was available for 82.7% of the cases. Those who underwent surgery only or radiation alone had 5-year survivals of 83.8% and 72.2%, respectively (p < 0.037). Multivariable analysis identified tumor size >4 cm, age > 40 years, male sex, Caucasian race, distant spread, and poorly differentiated grade as independent risk factors for mortality (p < 0.001). Conclusion: PC is a very rare tumor mostly affecting Caucasian individuals in the fifth decade. Older age, poor histologic differentiation, and distant metastasis are associated with a worse prognosis. Surgical resection offers the best survival outcome. To better understand the pathogenesis and factors affecting survival, all PC patients should be enrolled in national and international registries.

Ewing Sarcoma and Ewing-Like Sarcoma and the Role of NKX2.2 Immunoreactivity.

Ewing sarcoma (ES) belongs to the family of "small round blue cell" tumors and its diagnosis currently involves a combination of immunostaining and molecular analysis. However, due to significant histological overlap with other tumors of the same family, accurate diagnosis has historically involved combining these results with clinical correlation. Recently, multiple studies have analyzed the role of NKX2.2 immunopositivity in the diagnosis of ES. NKX2.2, a downstream target of the Ewing sarcoma breakpoint region-Friend leukemia integration 1 (EWSR1-FLI1) fusion, has been identified as a potential stain to differentiate ES and Ewing-like sarcoma from other small round blue cell tumors. In this study, we examine the histopathological interpretation of five patients. Four cases showed fluorescent in situ hybridization (FISH)-identified EWSR1 rearrangement. In one case, rearrangements of EWSR1 or FUS could not be detected, and a diagnosis of Ewing-like sarcoma was rendered. NKX2.2 was immunopositive in all five cases. Based on this limited dataset, NKX2.2 immunopositivity can significantly support the diagnosis of ES and has the potential to support the diagnosis of fusion-undetected Ewing-like sarcoma in appropriate clinical and histologic settings.

Metastatic Neuroblastoma Presenting as a Submandibular Mass with Mandibular Bone Involvement in a Three-Year-Old Child.

Although neuroblastoma is one of the most common extra-cranial tumors in the pediatric population, it is rarely seen as a metastasis to the mandibular bone. The following is a case report of a 3-year-old male who initially presented with a submandibular mass that was proven to be a poorly differentiated metastatic neuroblastoma through excisional biopsy. This report is one of the few case reports that demonstrates metastatic submandibular neuroblastoma with mandibular bone involvement in the pediatric population.