Medullary Thyroid Carcinoma This case was provided by Treant Hospital, Bethesda, Hoogeveen, The Netherlands ADS-01504 Rev. 001 © 2016 Hologic, Inc.  All rights reserved.

Overview Medullary Thyroid Carcinoma Sporadic or familial Tumor of the parafollicular C cells Elevated serum calcitonin levels Congo red stain for amyloid and immunohistochemical stains aid in the diagnosis Immunohistochemistry: Positive: calcitonin, CEA, chromogranin, synaptophysin Negative: thyroglobulin DeMay RM. The Art & Science of Cytopathology: Superficial Aspiration Cytology. 2nd ed. Chicago, IL: American Society for Clinical Pathology Press; 2012.

Overview Continued Differential Diagnoses: Hürthle Cell Carcinoma Papillary Thyroid Carcinoma Follicular Neoplasm Anaplastic Thyroid Carcinoma Nodular Goiter Amyloid Goiter Immunhistochemisty can help aid in the diagnosis. See previous slide. DeMay, RM. The Art & Science of Cyotpathology: Superficial Aspiration Cytology. 2nd ed. Chicago, IL: American Society for Clinical Pathology Press; 2012.

Malignant Findings Cytology Medullary Thyroid Carcinoma Isolated, noncohesive cells are the predominant pattern Cell clusters can be present Cells may be many different shapes: round, polygonal, plasmacytoid, and spindled Amyloid is frequently present and stains red with Congo red stain, but when polarized light is applied changes to apple-green Continued on next slide DeMay, RM. The Art & Science of Cyotpathology: Superficial Aspiration Cytology. 2nd ed. Chicago, IL: American Society for Clinical Pathology Press; 2012.

Malignant Findings Cytology Medullary Thyroid Carcinoma Binucleation and multinucleation common Nuclei eccentrically located and typically round to oval Spindle cell variant: elongated nuclei Chromatin is coarsely granular with small nucleoli (less frequently, prominent nucleoli) Cytoplasm commonly abundant and finely granular Nuclear pseudoinclusions may be seen DeMay, RM. The Art & Science of Cyotpathology: Superficial Aspiration Cytology. 2nd ed. Chicago, IL: American Society for Clinical Pathology Press; 2012.

Patient History 53-year-old male History of Multiple Endocrine Neoplasia-2 Family history of thyroid disease Ultrasound of left thyroid lobe appears as multilobular goiter with microcalcifications FNA of left thyroid performed Multiple Endocrine Neoplasia-2 syndrome (MNE-2) could involve: Multiple tumors of endocrine organs Autosomal dominant inheritance Can occur with pheochromocytoma. This tumor produces catecholamines, mostly adrenaline¹. It can be life-threatening and must be medically resolved prior to surgery. DeMay, RM. The Art & Science of Cyotpathology: Superficial Aspiration Cytology. 2nd ed. Chicago, IL: American Society for Clinical Pathology Press; 2012.

Cytologic Diagnosis: Follicular Lesion, Bethesda III Moderately cellular specimen ThinPrep® Pap Stain Sheets showing spindle cells with elongated nuclei Salt and pepper chromatin Absence of colloid

Cytologic Diagnosis: Follicular Lesion, Bethesda III ThinPrep® Pap Stain Single epithelial cells lacking intranuclear invaginations Small nucleoli present

Patient Follow-up Repeat thyroid FNA within microcalcifications Cytologic diagnosis: Suspect for medullary thyroid carcinoma, Bethesda V Remainder of sample in ThinPrep® vial used for Cellient® cell block

Cellient® Cell Block: CEA Stain Thyroglobulin is negative. Congo red to express amyloid is negative. Spindle cells with plasmacytoid appearances, salt and pepper chromatin pattern and absence of colloid were noted on cytology, as described in the first FNA. Strongly positive plasmacytoid and spindle cells are also seen with Synaptophysin, Chromogranin and TTF-1

Cellient® Cell Block: Calcitonin Stain The laboratory that donated the Cellient™ Cell Block image of Calcitonin stain would like to remain anonymous. Positive calcitonin staining confirms diagnosis of medullary thyroid carcinoma

Cellient® Cell Block: H&E Stain Cellular features are similar to those seen in previous specimens.

Additional Patient Follow-up FNA of cervical lymph node was performed Cytologic diagnosis: Malignant cells consistent with medullary thyroid carcinoma Patient underwent total thyroidectomy and cervical lymph nodectomy Microscopic examination of lymph node: epithelial cells are seen, cytologic examinations show similarities with the thyroid aspirates. The immunological profile of the Cellient embedded cell sample is the same as the thyroid lesion.

Macroscopic Thyroidectomy Left and right thyroidectomy and lymph nodectomy. The laboratory that donated the thyroidectomy images would like to remain anonymous.

Thyroidectomy: H&E Stain Arrow shows amyloid. Microscopic examination of the tumor: spindle cells and plasmacytoid cells present, amyloid is detected. The tumor is confined to the thyroid itself and is removed in toto. Lymph node metastasis present. The laboratory that donated the thyroidectomy H&E Stain image would like to remain anonymous. Histologic diagnosis: Bilateral medullary thyroid carcinoma with lymph angioinvasion

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