BackgroundThe significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients.Patients and methodsWe retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan–Meier method and compared between groups using log-rank test.ResultsOut of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8–8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4–28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1–21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2–37.0, P=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2–41.2, P=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations.ConclusionUncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.

SUMMARYAcute onset neuropsychiatric manifestations in hypopituitarism are uncommon. We report a case of a 60-year-old man who was a follow-up case of macroprolactinoma with hypopituitarism for the last 9 years. He was on medical treatment with cabergoline, thyroxine and depot testosterone. During the last 2 years he was non-adherent to medications especially cabergoline. He was hospitalised for 2 days through emergency services following acute onset psychosis. His pituitary hormone profile was suggestive of adrenal insufficiency, secondary hypothyroidism and hypogonadism. MRI of the hypothalamic pituitary region revealed a pituitary macroadenoma which was larger in size compared to the previous scan. Further, this lesion was compressing on the adjoining structures including optic chiasma. The patient was treated with intravenous fluids, hydrocortisone and thyroxine replacement therapy. With this treatment he completely recovered from psychosis within 48 h. BACKGROUND

Background: Outcomes of childhood hematolymphoid malignancies have improved several fold because of immunosuppressive chemotherapy and broad-spectrum antibiotics for managing febrile neutropenia. An apparent trade-off has been an increase in invasive fungal disease (IFD), affecting multiple organs. We report the diagnostic and therapeutic challenges in 8 children with lymphoid cancers who developed intracranial (IC) fungal abscesses between 2010 and 2017. Methods: Children below 15 years of age undergoing treatment for leukemia/lymphoma with clinicoradiologic and microbiologic evidence of IC fungal abscess were included. Demographic details, clinical profile, and management were retrospectively audited. Treatment was guided by European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions for IFD with therapeutic drug monitoring (TDM)-directed azole dosing, and surgical intervention. Results: Eight patients (4 B-cell acute lymphoblastic leukemia, 2 relapsed B-cell acute lymphoblastic leukemia, and 2 non-Hodgkin lymphoma) were eligible for analysis. Proven, probable, and possible IFDs were seen in 2 (25%), 4 (50%), and 2 (25%) patients, respectively. Proven IFDs were invasive mucormycosis with remaining having mold infections. Cerebrospinal fluid galactomannan was positive in all 4 patients in whom it was tested. TDM was possible in 5/8 (63%) patients. Antifungal therapy was given for a median period of 4.2 months with 5 (63%) patients having complete resolution. Three (37%) patients expired, of which 2 were attributable to IFDs. Conclusions: IC fungal abscesses in children can cause significant morbidity and mortality in children with hematolymphoid cancers. Evaluation of cerebrospinal fluid galactomannan may help in early diagnosis and therapy. Prolonged antifungal therapy steered by TDM can help achieve resolution in some cases.

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A 35-year-old lady was diagnosed with a left-sided breast cancer (infiltrating ductal carcinoma, grade 2, estrogen receptor/progesterone receptor positive, human epidermal growth factor receptor 2 negative). She received neoadjuvant anthracycline-based chemotherapy, followed by breast conserving surgery. Postoperatively she commenced weekly paclitaxel 80 mg/m 2 /week. After the 8 th dose, she presented with painful swelling of hands, feet and a bilateral symmetrical rash over the extensor surfaces of legs up to the knees-ill-defined macules, papules and pustules with surrounding erythema [Figures 1a and 1b]. She improved with a 5-day course of low dose oral prednisolone and an oral antibiotic. Chemotherapy was terminated and she was started on adjuvant tamoxifen.