Spinal melanoma with optic neuropathy -rare manifestation of Neurocutaneous melanosis and PET-MRI findings.

Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.

Evaluating the Diagnostic Efficacy of 99mTc-Methionine Single-Photon Emission Computed Tomography-Computed Tomography: A Head-to-Head Comparison with 11C-Methionine Positron Emission Tomography-Magnetic Resonance Imaging in Glioma Patients.

Background: Amino acid positron emission tomography (PET) imaging plays a significant role in the diagnosis of gliomas and in differentiating tumor recurrence from necrosis. In this study, the authors evaluated the diagnostic efficacy of [99mTc]Tc-methionine single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with [11C]methionine PET-magnetic resonance imaging (MRI) in delineating tumors. Methods: Thirty-one (primary: 16 and postoperative: 15) patients of confirmed (either MRI or histopathological proven) glioma underwent both [99mTc]Tc-methionine SPECT-CT and [11C]methionine PET-MRI. A comparative analysis was performed between SPECT, PET, and MR images to calculate the concordance between the modalities and to evaluate the diagnostic efficacy of the [99mTc]Tc-methionine SPECT. Results: [99mTc]Tc-methionine SPECT showed comparable uptake in the tumor lesions in comparison to [11C]methionine PET. A significant and strong positive correlation was observed between the volume of tumor (Vt) in PET and Vt MR (p < 0.004). Likewise, a significant and strong positive correlation was found between Vt SPECT and Vt MR. [99mTc]-methionine has a sensitivity and specificity of 91% and 75%, respectively, compared with 82% and 100% for [11C]methionine in postoperative cases to differentiate the tumor recurrence from necrosis. The sensitivity and specificity of [99mTc]Tc-methionine was 92% and 100%, respectively, compared with 92% and 67% for [11C]methionine in primary tumors. Conclusion: [99mTc]Tc-methionine SPECT-CT is as equally good as [11C]methionine for diagnosing and differentiating it from necrosis especially in high-grade glioma.

Bing Neel syndrome presenting as isolated cranial nerve palsies - a case report.

Background and aims: Waldenstroms macroglobulinemia (WM) is a low-grade B cell neoplasm. Bing Neel syndrome is a rare manifestation of WM characterized by infiltrative involvement of the central nervous system. Case report: 64-year-old man, presented with 4 years history of slowly progressive diplopia and ptosis of eyes. Examination showed left oculomotor (internal and external ophthalmoplegia), with trochlear, abducens, and right partial oculomotor and abducens nerve involvement. Evaluation showed anemia of hemoglobin 10.7 g/dL, raised erythrocyte sedimentation rate of 120 mm/h and plasma albumin:globulin reversal. Serum protein electrophoresis showed a paraprotein peak in the early gamma region with elevated IgM level (3810 mg/dL) and elevated free kappa light chain level (70.1 mg/L). Bone marrow aspiration from posterior iliac crest revealed mature small lymphocytes with positive immunohistochemical markers of CD5, CD10 negativity and MYD88 mutation positivity suggestive of WM. Patient was treated with bendamustine and rituximab regimen, with no neurological improvement at the end of one year. Conclusion: This case expands spectrum of paraproteinemic neuropathy to include cranial nerve palsy. Thus, plasma cell dyscrasias have to be considered in patients with isolated ophthalmoparesis especially in elderly patients, even with other comorbidities such as diabetes mellitus.

A Rare Case of Asymmetric Progressive Supra Nuclear Palsy Diagnosed In vivo with Magnetic Resonance/Positron Emission Tomography.

PSP and CBD are usually multi system sporadic disorders characterized by tau inclusions in neurons and glia. The clinical and neuroimaging features are different .However in some cases overlapping of features are noted. Here we present a case of a 65 years old female patient, presenting a 3 years history of insidious onset of asymmetric right upper and lower limb dystonia, followed by slowness, falls and injuries to the back, Parkinsonism, urinary incontinence and cognitive dysfunction and upward gaze palsy. MRI findings were suggestive of moderate cerebral and cerebellar atrophy with prominent ventricular system, reduced antero-posterior midline midbrain diameter, at the level of superior colliculus on axial imaging (morning glory sign was positive) on the left side. PET showed asymmetric hypo metabolism noted in the left superior and middle frontal gyrus, superior temporal and mid temporal gyrus in addition to striatum and thalamus, as well as midbrain, pons and right cerebellar hemisphere. Overall MR/PET was suggestive of unilateral PSP (left) and it corroborated with clinical history of unilateral dystonia and supranuclear gaze palsy. Based on MRI the differential considered was also CBD, but PET showed metabolic activity in the motor cortex. Additionally based on the hummingbird sign and morning glory sign a rare diagnosis of unilateral PSP could be made which also corroborated with the clinical picture.The case report emphasizes the utility of PETMRI simultaneously in situations like these to pick atypical variants or cases with overlapping pathology to reach a diagnosis with in vivo imaging methods.

The efficacy, toxicity and survival of salvage retreatment PRRT with 177Lu-DOTATATE in patients with progressive NET following initial course of PRRT.

OBJECTIVE: To evaluate the efficacy, toxicity and survival of salvage peptide receptor radionuclide therapy (PRRT) with indigenous, direct-route 177Lu-labelled-DOTATATE in metastatic Nueroendocrine tumor (NET) patients who showed an objective response or disease stabilization following initial course of 177Lu-DOTATATE PRRT cycles and eventually developed progressive disease after a time-interval of more than 1 year; the variables influencing survival and response of salvage PRRT were also examined. METHODS: A total of 26 progressive metastatic NET patients who received salvage PRRT with indigenous 177Lu-DOTATATE, were evaluated. Response was assessed under three broad categories as clinical symptomatic, biochemical and imaging (both molecular and morphological imaging). The Kaplan-Meier product-limit method was used to calculate progression-free survival (PFS) and overall survival (OS). Toxicity of salvage PRRT was evaluated by NCI-CTCAE v. 5.0 criteria (included complete blood counts, renal and liver function tests). Association between various variables and response and survival were analyzed using the χ2 test. RESULTS: Out of the 26 patients, the complete follow-up data were not available for four patients, where only survival information was available. Thus, a total of 22 patients (median age: 55 years, range: 38-68 years, 12 men and 10 women) were included and analyzed retrospectively in study. The cumulative dose of initial course of PRRT (I-PRRT) with indigenous 177Lu-DOTATATE ranged from 800 mCi (29.6 GBq) to 1231 mCi (45.54 GBq) per patient {mean administered cumulative dose of 964 mCi (35.66 GBq) per patient}, and the salvage PRRT with indigenous 177Lu-DOTATATE comprised of a mean dose of 170 mCi (6.29GBq) per patient. The disease control rate of 68.1%, 77.3%, 63.6% and 63.6% were observed after salvage PRRT on clinical symptomatic, biochemical, molecular and morphological imaging response respectively. The median PFS after salvage PRRT was 17 months. The median OS was not attained after I-PRRT (OS-i) and salvage PRRT (OS-s). Estimated OS-i rate was 68% at 108 months and OS-s rate was 82% at 18 months. None of the patients developed Grade 3/4 hematotoxicity, nephrotoxicity and hepatotoxicity or AML/MDS after I-PRRT and salvage PRRT at median follow-up of 72 months and 12 months respectively. The highest level of toxicity was Grade 2 [seen as reversible anemia, thrombocytopenia and nephrotoxicity in 3 (13.5%), 1 (4.5%) and 2 patients (9%) respectively]. The significant p-value was not observed for any variable association. CONCLUSION: With limited therapeutic options available for progressive NET after I-PRRT and in the absence of high-grade toxicity after 177Lu-DOTATATE salvage PRRT, retreatment with PRRT may be considered as a relatively safe therapeutic option for these patients. ADVANCES IN KNOWLEDGE: This study examined salvage retreatment PRRT with indigenous "direct-route" 177Lu-DOTATATE and registered its safety and survival benefits, indicating this could be an effective therapeutic option in this clinical setting.

Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting.

OBJECTIVES: Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. METHODS: A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10-12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. RESULTS: Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4-79.7%) and 79.4% 95% CI (71.4-86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. CONCLUSIONS: The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. ADVANCES IN KNOWLEDGE: The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.

Pulmonary Embolism as Post-COVID-19 Sequelae: Role of Lung Perfusion Scintigraphy.

We present the case of a 41-year-old male, suspected to have pulmonary thromboembolism with a history of coronavirus disease 2019 (COVID-19) infection 1 month ago. He presented with dyspnea and dry cough for 2 weeks. D-dimer was >776.70 mcg/L. Lung perfusion scan with Tc-99m macroaggregated albumin revealed multiple bilateral segmental perfusion defects with no mass lesion/consolidation on high-resolution computed tomography (CT) of lungs suggestive of pulmonary embolism (PE) present according to perfusion only modified PIOPED II criteria. CT pulmonary angiogram showed a large filling defect in the right pulmonary artery. The case emphasizes the prolonged sequelae following COVID-19 after recovery from the acute phase of the illness. Lung perfusion scintigraphy can play an important role in the screening of such patients who may be at risk for developing PE as post-COVID-19 sequelae.