Case 3 -

Parathyroid Autograft, Hyperfunctioning Celeste N. Powers Virginia Commonwealth University Health Systems Richmond, VA

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Clinical History 62 year old man presents with a 1.2 cm superficial abdominal mass that is hypervascular on ultrasound. No prior history of malignancy. Fine needle aspiration was performed using a 23 gauge needle. Cytologic Description Diff Quik stained FNA smears showed a moderately cellular sample of uniform cells arranged in small flat groups and loose arrays with scattered single cells and stripped nuclei. Intact cells had moderate amount of cytoplasm, round regular nuclei with inconspicuous nucleoli. Within the groups cells often had a follicular appearance and/or with nuclei in small linear arrangements. No mitoses were seen. The background was moderately bloody. Ultrasound image showed a discrete mass within the abdominal subcutaneous tissue. Case 3 - Figure 1 Case 3 - Figure 2 Case 3 - Figure 3 Case 3 - Figure 4 Case 3 - Figure 5 Case 3 - Figure 6 Case 3 - Figure 7 Differential Diagnosis The first impression without history or location was that these smears resembled thyroid follicular cells. Because the site was identified as abdomen and the nodule located within the subcutaneous tissue, further history was obtained. Review of the medical record revealed that the patient had end stage renal disease, hypertension and hypercalcemia. At age 56 he had undergone parathyroidectomies with concurrent autograft placement in the abdomen. Case 3 - Figure 8 Cell block Case 3 - Figure 9 PTH IHC With this information the differential was narrowed to a single diagnosis which was confirmed when immunohistochemistry performed on cell block material was positive for PTH. Final Diagnosis: Parathyroid autograft, hyperfunctioning Followup: The hyperfunctioning gland was ablated using alcohol. The patient, as an end stage renal disease patient, was on routine hemodialysis. He also suffered from significant coronary artery disease. Two months following this procedure he suffered a cardiac arrest with anoxic brain injury and succumbed shortly thereafter. Discussion: This case is presented not as a challenging unknown-since history was easily obtained resulting in a straightforward diagnosis. Rather the case is presented to discuss fine needle aspiration of the parathyroid glands which may be quite challenging. Parathyroid aspiration is increasing coincident with increasing utilization of ultrasound guided FNA and rapid "intraoperative" PTH testing. In the past was superficial fine needle aspiration was used infrequently to confirm the presence of parathyroid. Typically, they were "incidental findings" when FNA was used to evaluate intrathyroidal nodule identified radiologically. At that time imaging could detect PT glands greater than 1 cm which would include adenomas or hyperplasic glands. More recently, detection and sampling of even of 3mm nodules is possible using ultrasound fine needle aspiration (US-FNA). US-FNA has been of particular help in patients who remain hypercalcemic following neck exploration. In these situations hyperplastic parathyroid gland(s) may not have been identified or an adenoma may have been removed, yet the patient remains hypercalcemic. Thus preoperative localization of parathyroid glands allows for a very precise and direct "second" surgical approach or percutaneous alcohol ablation therapy. Most often, the PT appears as a rounded homogeneous mass with a lower echogenicity than that of the normal thyroid gland. Unfortunately, the cytomorphologic appearance of parathyroid follicular cells has considerable overlap with thyroid follicular cells and in some cases even "C" cells. Although there are some situations where cytomorphology may be all that is necessary, if enough material is available to perform immunochemistry on cell blocks or chemical analysis for parathyroid hormone on needle rinses (using minimal volume) to confirm the presence of parathyroid cells/tissue. The latter is often used when parathyroid cysts are encountered. These have a very classic appearance of water clear fluid that when examined is acellular. The cyst fluid when sent for chemical analysis has extremely high levels of parathyroid hormone which confirms the diagnosis. A textbook description of the classic appearance of parathyroid aspiration cytology suggests that differentiation between parathyroid follicular cells and thyroid follicular cells is not that challenging. However in practice it is much more daunting, especially since many of these aspirations are submitted as thyroid nodules. The following cytologic criteria are useful in identifying parathyroid: Moderate to high cellularity with scattered naked nuclei Acinar/organoid or follicular structures, sheets and papillary like arrangements Delicate frothy background (dispersed cytoplasm) Cells are smaller than thyroid with round smooth nuclei Granular cytoplasm and cytoplasmic vacuolization Nuclei may be overlapped, "molded" or stripped nuclei in short chains Nuclear hyperchromasia / stippled "neuroendocrine" chromatin Case 3 - Figure 10 PT aspiration with follicular arrangement, Note nuclear crowding Case 3 - Figure 11 Thyroid with honeycomb arrangement seen in non-neoplastic thyroid The honeycomb arrangement that signifies a non-neoplastic thyroid group is not typically seen in parathyroid aspiration the nuclei are often crowded or overlapped. Case 3 - Figure 12 PT cluster with cytoplasmic vacuolization Case 3 - Figure 13 Thyroid follicular cells with paravacuolar granules (not seen in PT) The presence of small clear vacuoles in the cytoplasm is a good criterion to use for parathyroid. The paravacuolar granules (lysosomes) seen occasionally in thyroid follicular cells. Case 3 - Figure 14 Follicular arrangement in parathyroid aspirate Case 3 - Figure 15 Irregular cluster of follicular cells in follicular neoplasm Hypercellular parathyroid aspirations with follicular architecture may be confused with thyroid cellular follicular lesions or follicular neoplasms. Although parathyroid cells are typically smaller than thyroid follicular cells, in a "pure" aspiration this size comparison is not available. Case 3 - Figure 16 Delicate capillary with stripped parathyroid nuclei Case 3 - Figure 17 Fibrovascular core with neoplastic thyroid follicular cells (PTC) Occasionally the thin delicate capillaries that are prevalent in parathyroid tissue will be aspirated and may be seen as stripped "cores" or have stripped nuclei or intact cells arranged around the vessels. In classic papillary carcinoma of the thyroid the fibrovascular cores are typically thicker and often have sheets of follicular cells or papillae at their tips. Case 3 - Figure 18 Anisonucleosis parathyroid Case 3 - Figure 19 Anisonucleosis thyroid In both thyroid and parathyroid aspirations anisonucleosis may be seen in scattered cells ("endocrine atypia"). This is not useful for distinction between the two glands. In addition, distinction between normal parathyroid and hyperplasia, adenoma or carcinoma is virtually impossible unless there is significant pleomorphism present in the latter. In these four diagnoses stripped nuclei will be present in the background since the cytoplasm is easily disrupted and dispersed; however, the traditional cracked colloid will not be present to any extent in pure parathyroid aspirations. In general most of the parathyroid adenomas will show some type of architectural pattern such as microfollicles and syncytia, while hypercellular (hyperplasia) parathyroids will be more likely to have sheets and syncytial clusters. When cystic degeneration occurs, hemorrhagic fluid, hemosiderin-laden macrophages and microfollicluar clusters can mimic cellular thyroid follicular lesions. Ancillary studies: Fortunately parathyroid hormone PTH and thyroglobulin and even calcitonin reliably distinguish parathyroid from thyroid follicular and C cells (medullary carcinoma), respectively. Immunochemistry is most reliable and reproducible on cell blocks or minicores thus tissue microfragments and needle rinses, when possible, should be processed as such. Scant material with conflicting morphology and limited radiologic information should result in a more generic interpretation. Parathyroid cells will also stain for chromgranin and synaptophysin. If limited material is available needle rinses- using minimal volume to avoid dilution- can be sent for chemical analysis for parathyroid hormone. If possible comparative serum samples should be sent as well. The needle rinses that are positive are substantially greater in concentration than the concomitant serum sample. Finally, fine needle aspiration of parathyroid adenomas does seem to have a greater degree of post aspiration tissue reaction, usually fibrosis, than thyroid. This fibrosis may be severe and even invade surround perithyroidal soft tissue and muscle. This causes difficulty during surgical resection and may mimic malignancy both from the surgeon's perspective as well as the surgical pathologist's. A history of FNA warrants caution to avoid overdiagnosis of parathyroid carcinoma, especially since these malignancies do not always show nuclear morphology characteristic of malignant neoplasms. Parathyroid Pattern Thyroid Mimic Hypercellular with microfollicles Follicular neoplasm Capillary cores with attached cells Papillary carcinoma (fibrovascular cores) Stippled chromatin Medullary carcinoma Cytomorphology Parathyroid Thyroid Smaller follicular cells Larger than PT cells Dispersed PT cytoplasm (no cracking) Thin watery colloid and/or cracked colloid Clear minute cytoplasmic vacuoles Paravacuolar granules References: Owens CL, Rekhtman N, Sokoll L, Ali SZ. Parathyroid hormone assay in fine-needle aspirate is useful for differentiating inadvertently sampled parathyroid tissue from thyroid lesions Diagn.Cytopathol. 2008;36:227–231. Norman J, Politz D, Browarsky I. 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