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

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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

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

9. 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

10. 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

11. 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

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

13. 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.

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

15. 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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