Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

INTRODUCTION Pembrolizumab(Keytruda) is a humanized IgG4 anti-programmed cell death-1 (PD-1) antibody serving as an immune-checkpoint inhibitor, now approved by FDA to treat several types of cancer. Although there are few reported cases of pembrolizumab induced new onset DKA in a non diabetic patients due to its autoimmune nature, its association in worsening glycemic control and DKA in pre-existing type 2 Diabetes mellitus is not well established. CASE 79 years old female with past medical hx of DM type 2 (Hba1c 7.4 was started on metformin), COPD(on chronic steroids and trilogy machine at home), recently diagnosed with poorly differentiated adenocarcinoma of the left lung, metastasis to liver, PDL 1 positive at 99%, started on palliative chemotherapy with Keytruda, 2 weeks after the third cycle of keytruda presented to the ED for AMS. Patient noted to be very dehydrated, somnolescent and tachypnea. Labs consistent with sugars > 600, potassium 6.8, Bicarb 5, Anion gap 33, beta hydroxybutyrate 11.5 (on 7/15/19 0.6), HbA1c 9.7,(On 12/15/16 7.3, 9/25/18 6.7, 1/22/19 7.4). PH 7.31, lactate 2.4. WBC count 21.5- no infectious source identified (CXR, CT brain, UA clean). Patient was admitted for DKA and treated with IV insulin and IV fluids. After medically stable patient was discharged with Insulin regimen. Within 5 days after being discharged, patient presented to ED again with DKA with PH 7.27, Bicarb 8, anion gap 22, sugars>600, beta hydroxybuterate 13.70. Patient was Rx for DKA- after a week of hospitalization was discharged to Hospice(due to metastatic cancer) and few weeks later expired.To summarize, pt with well controlled type 2 DM on metformin presented with frequent DKA 2 weeks after treatment with third cycle of keytruda leading to worsening glycemic control in-turn making patient Insulin dependent. CONCLUSION Incidence of Type 1 DM with pembrolizumab treatment is being increasingly recognized and reported, and DKA is a common initial presentation. However we need further studies to establish the mechanism of worsening glycemic control leading to Insulin dependent and DKA in patients with pre-existing type 2 diabetes. Also, physicians should counsel patients about this potential immune related adverse effect and educate them about the symptoms of hyperglycemia and DKA. REFERENCES Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review Jeroen M K de Filette1, Joeri J Pen2, Lore Decoster3, Thomas Vissers4, Bert Bravenboer1, Bart J Van der Auwera5, Frans K Gorus5, Bart O Roep6,7, Sandrine Aspeslagh3, Bart Neyns3, Brigitte Velkeniers1 and Aan V Kharagjitsingh1,2,5,8 Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes. Anupam Kotwal1, Candace Haddox2, Matthew Block3, Yogish C Kudva1. BMJ open Diabetes and research, Vol 7, issue1.

209 Background: Hormonal therapies function through CDK4/CDK6/E2F axis which is essential in luminal estrogen receptor positive breast cancer. Reactivation of these CDK4 and CDK6 kinases has been implicated in endocrine resistance. Many CDK 4/6 inhibitors were employed in studies with noteworthy safety concerns. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention GI symptoms and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: We included five RCTs with a total of 2671 patients treated with CDK 4/6 inhibitors. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arm used placebo in combination with letrozole or fulvestrant. The relative risks (RR) of all-grade side effects were as follows: diarrhea, 1.72 (95% CI: 1.08 – 2.74, p = 0.02); stomatitis, 2.62 (95% CI: 1.43 – 4.79, p = 0.002); nausea, 1.59 (95% CI: 1.30–1.94; p < 0.0001); vomiting, 1.65 (95% CI: 1.06–2.56; p = 0.02); elevated AST, 2.30 (95% CI: 1.34–3.93; p = 0.002); and elevated ALT, 2.78 (95% CI: 1.90–4.08; p < 0.0001). The RR of high-grade side effects were as follows: diarrhea, 2.26 (95% CI: 0.39 – 13.09, p = 0.36); stomatitis, 2.14 (95% CI: 0.36 – 12.72, p = 0.40); nausea, 1.13 (95% CI: 0.28 –4.47; p = 0.86); vomiting, 0.79 (95% CI: 0.24 – 2.54; p = 0.69); elevated AST, 1.85 (95% CI: 0.74 – 4.64; p = 0.18); and elevated ALT, 4.33 (95% CI: 2.15 – 8.71; p < 0.0001). Conclusions: The risk of developing any-grade diarrhea, stomatitis, nausea, vomiting and elevated AST and ALT, was high in CDK 4/6 inhibitors based regimen. Moreover, it increased the risk of high-grade elevated ALT.

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