Ans. D. Medullary. (Ref. Robbin's pathology 8,h/pg. 771; harrison's medicine 17th/pg. Table 77-5 )Robbin's pathology 8th/pg. 771......."Sporadic cases of medullary carcinoma present most often as a mass in the neck, sometimes associated with compression effects such as dysphagia or hoarseness. In some instances the initial manifestations are caused by the secretion of a peptide hormone (e.g., diarrhea caused by the secretion of VIP). Notably, hypocalcemia is not a feature, despite the presence of raised calcitonin levels. Screening of relatives for elevated calcitonin levels or RET mutations permits early detection of tumors in familial cases. All MEN-2 kindred carrying RET mutations are offered prophylactic thyroidectomies to preempt the development of medullary carcinomas;. Recent studies have shown that specific RET mutations correlate with an aggressive behavior in medullary carcinomas".Harrison's medicine l7th/pg. 2246.........."Elevated serum calcitonin provides a marker of residual or recurrent MCT".Medullary carcinomas of the thyroid# Introduction: Neuroendocrine neoplasms derived from the parafollicular cells, or C cells, of the thyroid.# Genetics: Both familial and sporadic medullary forms demonstrate activating RET mutations. Sporadic medullary carcinomas, as well as FMTC, occur in adults.# Distinct features:- Like normal C cells, medullary carcinomas secrete calcitonin, the measurement of which plays an important role in the diagnosis and postoperative follow-up of patients.- In some cases, the tumor cells elaborate other polypeptide hormones such as somatostatin, serotonin, and vasoactive intestinal peptide (VIP).- Medullary carcinomas arise sporadically in about 80% of cases. The remaining 20% are familial cases occurring in the setting of MEN syndromes 2A or 2B, or familial medullary thyroid carcinoma (FMTC) without an associatedMEN syndrome.- Multicentricity is particularly common in familial cases.- Acellular amyloid deposits, derived from altered calcitonin molecules, are present in the adjacent stroma (distinctive feature).- Electron microscopy reveals variable numbers of intracytoplasmic membrane-bound electron-dense granules. One of the peculiar features of familial is the presence of multicentric C-cell hyperplasia in the surrounding thyroid parenchyma, a feature usually absent in sporadic lesions.# Management: primarily surgical. Unlike tumors derived from thyroid follicular cells, these tumors do not take up radioiodine. External radiation and chemotherapy may provide palliation in advanced disease.Thyroid Neoplasms# Most thyroid neoplasms present as solitary thyroid nodules;# Only 1% of all thyroid nodules are neoplastic.# Follicular adenomas are the most common benign neoplasms.0# Papillary carcinoma is the most common malignancy.0# Multiple genetic pathways are involved in thyroid carcinogenesis. Some of the genetic abnormalities that are fairly unique to thyroid cancers include:- PAX8-PPAR71 fusion = follicular carcinoma.- Chromosomal rearrangements involving the RET oncogene = papillary cancers &- Mutations of RET = medullary carcinomas.0# Follicular adenomas and carcinomas are both composed of well-differentiated follicular epithelial cells, and are distinguished by evidence of capsular and/or vascular invasion in the latter.0# Papillary carcinomas are recognized based on nuclear features (ground-glass nuclei, pseudo-inclusions) even in the absence of papillae. Psammoma bodies are a characteristic feature of papillary cancers; these neoplasms typically metastasize via lymphatics but their prognosis is excellent.# Medullary cancers are nonepithelial neoplasms arising from the parafollicular C cells and can occur in either sporadic (80%) or familial (20%) settings. Multicentricity and C-cell hyperplasia are features of familial cases. Amyloid deposits are a characteristic histologic finding.# Anaplastic carcinomas are thought to arise by dedifferentiation of more differentiated neoplasms. They are highly aggressive, uniformly lethal cancers.Multiple endocrine neoplasiaMEN1IVIEN2Mixed Syndromes1. Parathyroid hyperplasia or adenoma2. Pancreatic Islet cell hyperplasia, adenoma, or carcinoma3. Pituitary hyperplasia or adenoma4. Other less common manifestations: foregut carcinoid, pheochromocytoma, subcutaneous or visceral lipomasA. MEN2A1. MTC2. Pheochromocytoma3. Parathyroid hyperplasia or adenomaB. MEN2A with cutaneous lichen amyloidosisC. MEN2A with Hirschsprung diseaseD. Familial MTCE. MEN2B1. MTC2. Pheochromocytoma3. Mucosal and GI neuromas4. Marfanoid featuresA. Von Hippel-Lindau syndrome1. Pheochromocytoma2. Islet cell tumor3. Renal cell carcinoma (B/L)4. Hemangioblastoma of CNS5. Retinal angiomasB. Neurofibromatosis with features of MEN1 or 2C. Carney complex1. Myxomas of heart, skin, and breast2. Spotty cutaneous pigmentation3. Testicular, adrenal, and GH- producing pituitary tumors4. Peripheral nerve schwannomas