| Abstract|| |
Parathyroid lesions clinically manifest themselves in the form of primary hyperparathyroidism most of the times. Parathyroid adenoma constitutes one of the important causes of the same. Although rare, they pose considerable diagnostic dilemma to the pathologist. A 50-year-old female presented to the surgical outpatient of our hospital with a history of recurrent pancreatitis. Clinical examination revealed a mass in the neck which was radiologically demonstrated as right inferior parathyroid mass. The same mass was surgically excised and histopathological features are discussed in this report.
Keywords: Adenoma, atypical, parathyroid
|How to cite this article:|
Ramaswamy AS, Vijitha T, Kumarguru B N, Mahalingashetti PB. Atypical parathyroid adenoma. Indian J Pathol Microbiol 2017;60:99-101
| Introduction|| |
Atypical adenomas of the parathyroid gland are a rare entity. Although these tumors have some of the features of carcinomas, they lack unequivocal evidence of invasive growth. Patients with atypical adenomas generally present with calcium levels intermediate between those of adenomas and carcinomas. On the basis of studies reported in literature, atypical adenomas pursue a benign clinical course. The molecular phenotype of atypical adenomas is intermediate between that of adenomas and carcinomas. Hence, those tumors whose features are worrisome, but not diagnostic of malignancy, fall under the rubric of “atypical adenoma.”
| Case Report|| |
A 50-year-old woman came to the surgical outpatient department with a history of recurrent pancreatitis and a known case of hyperparathyroidism on treatment. During her previous admission for management of pancreatitis, it was observed that her serum calcium level was 14.1 mg/dL. Intact parathyroid hormone (PTH) level was 104.9 pg/ml. Local examination [Figure 1]a revealed a soft to firm single nodule measuring 2 cm × 1 cm in right lobe of thyroid.
|Figure 1: (a) Clinically visible swelling in front of the neck in the region of right lobe of thyroid. (b) Thyroid ultrasound examination showing two hypoechoic nodules in the inferoposterior aspect of right lobe of thyroid. (c and d) TC-99M sestamibi scan showing an evidence of abnormal accumulation of tracer inferior to the right thyroid lobe, suggestive of a parathyroid adenoma|
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Biochemical tests at the time of her current admission showed severe hypercalcemia with serum calcium (17.7 mg/dL) and reduced phosphate (2.4 mg/dL) levels. Thyroid function test levels were T3 0.60 ng/ml, T4 5.25 µg/dL, and thyroid-stimulating hormone (TSH) 1.14 mIU/L.
Thyroid ultrasound examination revealed two hypoechoic nodules [Figure 1]b adjacent to each other in the inferoposterior aspect of right lobe of thyroid measuring 1.9 cm × 1.5 cm and 0.6 cm × 0.7 cm.
Ultrasound-guided fine-needle aspiration cytology showed features such as acinar pattern of uniform-sized cells with scant to moderate amount of granular cytoplasm, round nuclei with salt and pepper chromatin, and visible nucleoli. Benign neuroendocrine tumor was the impression given. Cell block study also showed similar cells in acinar and discohesive pattern and no mitotic figures.
TC-99M sestamibi scan [Figure 1]c and [Figure 1]d showed an evidence of abnormal accumulation of tracer inferior to the right thyroid lobe which was suggestive of the presence of a parathyroid adenoma.
Right inferior parathyroid excision with right hemithyroidectomy with central group lymph node dissection was done and specimen sent for histopathological examination. Intraoperatively, a single 5 cm × 4 cm, grayish hard mass was noted in the inferior parathyroid region, infiltrating carotid strap muscles with no plane between the right lobe and the mass.
Grossly the specimen [Figure 2] in total measured 5 cm × 3.5 cm × 1 cm. Cut section revealed a well-circumscribed lesion in the right lobe of thyroid measuring 3 cm × 2.5 cm, composed of multiple nodules interspersed by fibrous bands and foci of chalky calcification.
|Figure 2: Cut section showing a well-circumscribed lesion composed of multiple nodules interspersed by fibrous bands and foci of chalky calcification|
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Microscopic features studied from multiple sections showed an intrathyroidal lesion, well circumscribed, unencapsulated with pushing borders. Lesion was composed of varying sized nodules of tumor cells. Entrapped normal thyroid follicles were noted in between the tumor nests [Figure 3]a. Tumor cells were arranged in nests and trabecular patterns. Thin capillary network was seen traversing between the tumor cells. Polygonal to round tumor cells with moderate to abundant granular pink cytoplasm, with varying degree of nuclear pleomorphism and prominent macronucleoli were seen. Focal areas of necrosis and dystrophic calcification [Figure 3]b were noted. Intranuclear pseudoinclusion [Figure 3]c and 5 mitoses/50 HPF were also seen. The tumor cell nests were intersected by broad thick fibrous bands. There was no evidence of any vascular or perineural invasion. The margins of the specimen do not show involvement by the tumor. No normal parathyroid tissue was identifiable in the given specimen. No metastasis was noted in the lymph node. Final impression was given as an atypical parathyroid adenoma.
|Figure 3: (a) Intrathyroidal lesion composed of varying sized nodules of tumor cells (H and E, ×100). (b) Focal areas of tumor necrosis and tumor cell nests being intersected by broad thick fibrous bands (H and E, ×100). (c) Nests of tumor cells showing intranuclear pseudoinclusion (black arrow) (H and E, ×400)|
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Postoperative calcium levels were 12.7 mg/dL (day 1), 11.6 mg/dl (day 2), 11.3 mg/dl (day 3), 10.5 mg/dl (day 4), 9.9 mg/dl (day 5), 10.2 mg/dl (day 6), and 9.3 mg/dL (day 7). Thyroid function tests revealed T3 1.43 ng/mL, T4 5.48 µg/dL, and TSH 0.71 mIU/L postoperatively.
| Discussion|| |
Parathyroid adenomas are the single most common cause of primary hyperparathyroidism. The incidence of parathyroid adenoma is reported to be about 85%. The most frequent symptoms are weakness, fatigue, anorexia, nausea, vomiting, polydipsia and polyuria, loss of weight, dyspepsia, constipation, and headaches. Bone, joint, muscular pain, pathological fractures, and renal stones are also common when hyperparathyroid state is prolonged and severe. Recurrent severe pancreatitis, anemia, and peptic ulcer disease can also occur in the later stages.
Clinically patients with primary hyperparathyroidism present with osseous manifestations (varying from initial decrease in bone density to full blown osteitis fibrosa cystica), few with renal manifestations, and rarely with other manifestations, namely, hypertension, acute and chronic pancreatitis, peptic ulcer, and mental disturbances.
Most commonly one sees primary hyperparathyroidism that occurs as a result of adenomas (80%–85%), hyperplasias (10%–15%), or carcinoma (1%) of the parathyroid glands. Atypical parathyroid adenoma or parathyroid neoplasm of uncertain malignant potential is a rare histopathologic entity. The presence of two or more of the following attributes will lead to this diagnosis: incomplete invasion of the capsule, fibrous bands, pronounced trabecular growth, mitotic activity >1/10 HPF, tumor necrosis without unequivocal signs of capsular or vascular invasion. The presence of mitosis should certainly lead to further investigation toward the elimination of malignancy.,,
These tumors may be adherent to the adjacent thyroid or surrounding soft tissues. Intrathyroidal location of parathyroid can cause diagnostic dilemma. Follow-up of these cases has demonstrated a benign outcome in most, following local excision. Few studies revealed that the phenotypes p27(+), bcl2(+), Ki-67(–), and mdm(+) were present in 76% and 29% of typical and atypical adenomas, respectively, and in no cases of carcinoma.
The easiest way to separate hyperplasia and adenoma is to sample more than one gland. If more than one gland is enlarged or abnormal, if there is an increase in the parenchyma to fat ratio, and nodular distribution of both the chief and oncocytic cells, then hyperplasia should be considered., Clinical information about renal status, serum calcium levels, intraoperative serum PTH levels will help make the separation. Overall, the adenoma and hyperplasia diagnoses are to a great extent based on the macro- and/or microscopic findings in the remaining associated glands.
Parathyroid adenoma is grossly smooth, encapsulated mass with rim of uninvolved parenchyma adjacent to proliferation. Microscopically, a single histologic population of enlarged cells, glandular architecture with secretions, atrophy, or compression of parathyroid parenchyma are seen., Immunohistochemical results are parathormone and chromogranin positive.
Parathyroid carcinoma usually has a trabecular architecture, thick acellular bands of fibrosis, capsular/vascular/perineural invasion, profound nuclear pleomorphism, prominent eosinophilic macronucleoli, increased atypical mitotic figures, and presence of comedo necrosis. Adherence to the thyroid gland, difficulty in removing the tumor and extremely elevated serum calcium levels should elevate suspicion of parathyroid carcinoma.
Thyroid lesions can cause diagnostic difficulty. Immunohistochemical staining for PTH, thyroid transcription factor-1, or thyroglobulin is helpful in this discrimination.
The distinction between an atypical parathyroid adenoma and parathyroid carcinoma can be quite a difficult one. Clinical findings in addition to the histological appearance should give the clue to correct diagnosis.
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Dr. Anikode Subramanian Ramaswamy
52, Vignesh Nilayam, 11th Cross, T.C. Palya, K.R. Puram, Bengaluru - 560 036, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]