Histopathologic Diagnosis of Neuroendocrine Neoplasms of Head and Neck, Lung and Gastrointestinal Tract

Neuroendocrine neoplasms are classified as epithelial and non-epithelial based on their origin being from epithelial neuroendocrine progenitor cells or derived from the neural crest. The latter are negative for cytokeratin (hence non-epithelial) and mostly result from neoplastic transformation of paraganglia. Here, we are reviewing the most important histologic and immunophenotypic characteristics of neuroendocrine carcinomas as well as the current WHO classification guidelines. The terminology of neuroendocrine neoplasms is confusing due to various classification systems employed for each internal organ. In the lung and GI tract, for example, “neuroendocrine tumors” comprise carcinomas of different degree of differentiation and histologic grade. While in the lung the term refers strictly to low-grade neuroendocrine carcinomas, in the GI tract it comprises both low- and high-grade neuroendocrine carcinomas. Despite concerted efforts to unify the overall classification of neuroendocrine carcinomas across organs, major differences continue to persist

Deep and Prolonged Response to Aurora A Kinase Inhibitor and Subsequently to Nivolumab in MYCL1-Driven Small-Cell Lung Cancer: Case Report and Literature Review

Small-cell lung carcinoma (SCLC) is one of the most aggressive solid tumors, and the prognosis has not improved significantly in 25 years. Despite a recent understanding of the genomic aberrations seen in SCLC, these insights have not led to any breakthroughs in treatment. We present a patient with SCLC harboring a novel MYCL1 fusion protein who experienced a prolonged disease course due to the use of Aurora A kinase inhibitor and subsequently nivolumab. MYC family genes are master regulators of several cellular pathways including proliferation, differentiation, and apoptosis and recently have been shown to be involved in tumor immune evasion. Large studies have shown that a significant proportion of patients with SCLC have amplification or overexpression of MYC family genes. Preclinical data have exposed vulnerability of MYC-driven tumors to Aurora kinase inhibitors, bromodomain and extraterminal domain inhibitors, and recently to immune checkpoint blockers. Further studies using these agents with selective enrolling of patients with MYC-altered tumors are warranted to exploit these vulnerabilities

Primary calcitonin-secreting neuroendocrine carcinoma of the larynx - Case report and update on current terminology

Primary calcitonin-secreting neuroendocrine carcinoma of the larynx is a rare neuroectodermal neoplasm currently classified as moderately differentiated (atypical carcinoid/WHO classification) neuroendocrine carcinoma of the larynx. Due to the rarity of these tumors at this location as well as their distinctive histologic and immunophenotypic features, they often raise significant diagnostic difficulties in biopsy specimens. We present a 57-year-old woman with persistent and gradually worsening pharyngeal pain for approximately one year duration, who was found to have a lesion limited to the right aryepiglottic fold. Final pathology showed moderately differentiated neuroendocrine carcinoma. Due to calcitonin positivity and coexistence of a thyroid nodule, the tumor raised the differential diagnosis of medullary thyroid carcinoma. A practical approach to pathologic diagnosis of laryngeal neuroendocrine tumors and discussion of clinical management is provided

Analysis of Vitamin D Status at Two Academic Medical Centers and a National Reference Laboratory: Result Patterns Vary by Age, Gender, Season, and Patient Location

Background: Testing for 25-hydroxyvitamin D [25(OH)D] has increased dramatically in recent years. The present report compares overall utilization and results for 25(OH)D orders at two academic medical centers - one in New York and one in Iowa – in order to characterize the vitamin D status of our inpatient and outpatient populations. Results are also compared to those from a national reference laboratory to determine whether patterns at these two institutions reflect those observed nationally. Methods: Retrospective data queries of 25(OH)D orders and results were conducted using the laboratory information systems at Weill Cornell Medical College / New York Presbyterian Hospital (WCMC), University of Iowa Hospitals and Clinics (UIHC), and ARUP Laboratories (ARUP). Chart review was conducted for cases with very high or low serum 25(OH)D levels in the WCMC and UIHC datasets. Results: The majority of tests were ordered on females and outpatients. Average serum 25(OH)D levels were higher in female versus male patients across most ages in the WCMC, UIHC, and ARUP datasets. As expected, average serum 25(OH)D levels were higher in outpatients than inpatients. Serum 25(OH)D levels showed seasonal periodicity, with average levels higher in summer than winter and correlating to regional UV index. Area plots demonstrated a peak of increased 25(OH)D insufficiency / deficiency in adolescent females, although overall worse 25(OH)D status was found in male versus female patients in the WCMC, UIHC, and ARUP datasets. Surprisingly, improved 25(OH)D status was observed in patients starting near age 50. Finally, chart review of WCMC and UIHC datasets revealed over-supplementation (especially of ≥ 50,000 IU weekly doses) in the rare cases of very high 25 (OH)D levels. General nutritional deficiency and/or severe illness was found in most cases of severe 25(OH)D deficiency. Conclusions: 25(OH)D status of patients seen by healthcare providers varies according to age, gender, season, and patient location. Improved 25(OH)D status was observed later in life, a finding that may reflect the previously described increased use of vitamin D-containing supplements in such populations. Severe vitamin D deficiency is much more common than vitamin D toxicity

Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathological parameters were determined for each patient. The molecular profile was investigated using next-generation sequencing (NGS). Histologically, all tumors were hypercellular neoplasms with spindle-shaped or sarcomatoid cells. All patients showed vascular and perineural invasion. Most patients had a poor prognosis. NGS showed important similarities with conventional PDAC, including frequent alterations in the classic PDAC drivers, KRAS (100% of cases), TP53 (90%), and CDKN2A (60%). There were also some important distinctions from conventional PDAC: 1) SMAD4, a typical PDAC driver gene, was mutated in only one case (10%); 2) Another distinctive molecular feature was the recurrent KRAS amplification (30% of cases), which is very rare in conventional PDAC. It has been previously reported in another subtype of pancreatic undifferentiated carcinoma, the rhabdoid variant, and may be a key event leading to the acquisition of an undifferentiated phenotype in a subgroup of cases; 3) Lastly, in two different cases, we detected two potentially actionable targets, not belonging to the typical PDAC molecular landscape, such as MCL1 amplification and POLQ mutation. Our study sheds light on this rare tumor type, which shows aggressive biological behavior and few druggable alterations. The most distinctive molecular features of pancreatic USC are the paucity of SMAD4 alterations and recurrent KRAS amplification