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Combined Approaches (Neelakantan et al., 2022): NNMT inhibition with reduced-calorie diet produced dramatic adiposity reduction in DIO mice, normalizing metabolic parameters and establishing a distinct gut microbiome

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occasionally interrupted, thin collagen layer with soft tissue invasion Microscopic Pathology Delicate chromatin/small nucleoli/rare mitoses (benign) Vesicular nuclei/coarse chromatin/violaceous macronucleoli, frequent mitoses (malignant) Pigmentation variable or patchy Plus psammomatous calcifications in psammomatous variant Ancillary Tests Reticulin outlines lobules S100, HMB-45, Melan-A, tyrosinase positive Collagen IV and laminin outline basal lamina around lobules Top Differential Diagnoses Conventional schwannoma Contain lipofuchsin (PAS[+]) but lack melanin Pigmented neurofibroma Typically diffusely infiltrative Melanocytoma Lack long-spacing collagen Primary or metastatic melanoma Cytologically malignant Clear cell sarcoma (soft tissue melanoma) No immunohistochemical or ultrastructural basal lamina TERMINOLOGY Synonyms Pigmented schwannoma Melanogenic schwannoma Melanogenic nerve sheath tumor Definitions Usually benign, often circumscribed tumor of melanin-producing Schwann cells CLINICAL ISSUES Epidemiology Incidence Sporadic Syndromic (Carney complex) Frequent mutation of tumor suppressor gene PRKAR1A Age Childhood to senescence (mean: 35 years) A decade younger in patients with Carney complex Gender Slight female predominance (1.5:1) in both sporadic and syndromic types Site Sporadic Spinal nerves and ganglia (cervicothoracic) Rarely multiple Syndromic (Carney complex) Alimentary tract Viscera (heart, liver, lung) Bone 15% multiple Presentation Sporadic Nerve root associated tumors: Pain or sensory disturbance Syndromic (Carney complex

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