Atypical presentation of oncocytic parathyroid adenoma masquerading as metastatic carcinoma.

Parathyroid carcinoma is the rarest endocrine malignancy. Definitive diagnosis is challenging as it is difficult to distinguish malignant from benign disease. A 71-year-old man presented with weight loss and hypercalcaemia. CT scans revealed multiple lung nodules and lytic bone lesions that were consistent with metastatic dissemination. Technetium-99m-sestamibi-single-photon emission computed tomography scan showed an abnormal uptake in the right thyroid lobe. Fine-needle aspiration (FNA) was performed on three occasions. The patient underwent parathyroidectomy with ipsilateral hemithyroidectomy without postoperative complications. Microscopic examination showed a parathyroid neoplasm with fibrosis and intravascular tumour on a background of unremarkable thyroid parenchyma. This resulted in an initial impression of parathyroid carcinoma. Further review by two independent pathologists provided a final diagnosis of oncocytic parathyroid adenoma. This case highlights the subjectivity and interobserver variation with endocrine histological examination. FNA can induce changes that mimic parathyroid carcinoma on histology. An index of suspicion for benign parathyroid adenomas should be maintained.

Metastases to the Parathyroid Glands: A Comprehensive Literature Review of 127 Reported Cases.

Metastases to the head and neck organs are uncommon, potentially representing the initial presentation of an occult malignancy. Single case reports and small series report metastases to the parathyroid gland, but there is no large review of the literature on secondary tumors involving the parathyroid glands. A review of the English literature between 1950 and 2017 was performed of all metastases or secondary involvement of the parathyroid glands. One hundred and twenty-seven cases of metastatic tumors were reported, although potentially significantly unrepresented in autopsy series (parathyroid glands are not routinely examined) and due to reporting bias. Women were affected more commonly than men (5.8:1; 99 vs. 17, respectively), with a mean age at presentation of 58.5 years, when reported. The most common primary sites of malignancies that metastasized to the parathyroid glands were breast carcinomas (66.9%, n = 85), melanoma (11.8%, n = 15), and lung carcinoma (5.5%, n = 7), with carcinomas representing 86.6% of metastases. Metastases were nearly always identified as part of widely metastatic disease, with only five (3.2%) cases reported as isolated metastases. Tumor-to-tumor metastases comprised 5.5% of all metastases to the parathyroid glands (metastases to parathyroid adenoma). A significant clinical finding of metastases to the parathyroid glands was the development of deranged calcium homeostasis, well beyond the 9 (7.2%) cases with primary parathyroid gland disease present. Although concurrent conditions (renal disease; bone metastases) may partially affect calcium metabolism, the onset of calcium derangement seemed to coincide with parathyroid gland metastases and not systemic disease. In summary, metastases to the parathyroid glands are uncommon, potentially under-recognized in patients who have otherwise widely metastatic tumors. Women are affected more often than men, with breast carcinomas (66.9%) and melanoma (11.8%) the most common primary tumors. Calcium homeostasis is affected, probably as a result of parathyroid gland parenchymal destruction.

Primary and metastatic parathyroid malignancies: a rare or underdiagnosed condition?

OBJECTIVE: Parathyroid gland malignancies are considered rare. The most common of these tumor types is primary parathyroid carcinoma. Metastatic spread from other cancers may also occur with up to 10% of cancers from other sites showing parathyroid involvement at autopsy. Tumor-to-tumor metastases (metastatic spread to parathyroid neoplasm) from remote cancers to the parathyroid gland have been described. METHODS: We did a PubMed literature review and analysis of our own experience of 392 consecutive parathyroidectomies. RESULTS: Primary and secondary parathyroid malignancies can be grouped into three categories: primary parathyroid carcinoma (PPCa), spread of carcinoma into parathyroid glands by contiguous extension from the thyroid gland or other head and neck cancer, and metastatic disease to the parathyroid gland from distant cancers. Studies of tumor-to-tumor spread indicate a predilection of spread to endocrine tumors possibly because of the rich blood supply that is present in endocrine tumors. Two of our 392 parathyroidectomies (0.5%) had cancer: one metastatic (thymic neuroendocrine tumor) and another PPCa. CONCLUSION: Metastatic disease to the parathyroid gland is poorly documented. When performing surgery for primary thyroid cancer, the search for parathyroid gland metastases is often overlooked because of the desire to preserve parathyroid function. Metastatic disease from other cancers to a benign parathyroid gland or to a parathyroid adenoma probably suggests a grave prognosis because it likely indicates widespread metastatic disease; however, isolated metastases to the parathyroid may occur. Although these lesions may be uncommon they may not be as rare as once thought.

Neuroendocrine thymic carcinoma metastatic to the parathyroid gland that was reimplanted into the forearm in patient with multiple endocrine neoplasia type 1 syndrome: a challenging management dilemma.

OBJECTIVE: To describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma. METHODS: Our patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5 cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient's forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography-computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones. RESULTS: We decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia. CONCLUSION: Metastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma.

Concurrence of primary hyperparathyroidism and metastatic breast carcinoma affected a parathyroid gland.

OBJECTIVE: Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia. CASE REPORT: A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland. CONCLUSION: This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.

Parathyroid involvement in thyroid cancer: an unforeseen event.

BACKGROUND: Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. METHODS: We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5%) were identified. Patient and tumor characteristics were recorded. RESULTS: Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. CONCLUSIONS: Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

Tumor-to-tumor metastasis: Hepatocellular carcinoma metastatic to parathyroid adenoma.

Tumor-to-tumor metastasis is a rare, but well-recognized phenomenon. Here, we report a unique case of hepatocellular carcinoma (HCC) metastatic to parathyroid adenoma. A 53-year-old-man with a history of HCC presented with hypercalcemia. It was found that he also had hyperparathyroidism with a hypoechoic mass in the lower portion of the right thyroid gland area. The patient underwent parathyroidectomy, and a mass measuring 1.5 × 1.0 cm was detected. Microscopic and immunohistochemical examination disclosed parathyroid adenoma with a focus of metastatic HCC. For the patient, it was the only distant metastasis revealed until the last follow-up. To the best of our knowledge, this is the first reported case of tumor-to-tumor metastasis in which HCC is the donor.

Metastatic parathyroid carcinoma initially misdiagnosed as parathyroid adenoma: the role of parafibromin in increasing diagnostic accuracy.

Parathyroid carcinoma, although a rare cause of primary hyperparathyroidism, carries a significant morbidity and mortality from severe symptomatic hypercalcaemia and related complications. We report a case where the diagnosis was not considered from the outset and review the current clinical and histopathological markers available to assist in the diagnosis of parathyroid carcinoma.

Metastatic breast carcinoma to parathyroid adenoma on fine needle cytology sample: report of a case.

Metastases to the thyroid gland diagnosed by means of fine needle cytology or by excision have been reported in the literature. To our knowledge, metastatic neoplasms to the parathyroid gland have never been described up to now. In this article, we introduce a rare case of metastatic breast carcinoma to a parathyroid adenoma in a 56-year-old woman, which clinically simulated a left thyroid nodule. The patient had a history of left breast carcinoma; the recent discovery of a palpable mass in the left thyroid area had elicited fine needle cytology sampling for its diagnostic evaluation. The obtained cytopathological sample was cellular but limited to a single Diff-Quik-stained smear; hence, no ancillary studies could be entertained. A cytopathological diagnosis of positive for malignant cells of query metastatic breast origin was performed. The permanent histopathological examination of the surgical sample disclosed multiple small foci of metastatic high-grade carcinoma of ductal type within a somewhat atypical adenoma of the parathyroid gland. The cytopathological findings and some differential diagnostic considerations are briefly commented, as well as the deranging imaging data concerning this interesting case.

Clinical significance of extrathyroid extension to the parathyroid gland of papillary thyroid carcinoma.

Extrathyroid extension is a prominent prognostic factor of papillary thyroid carcinoma (PTC). In the UICC TNM classification, minimal extension to the sternothyroid muscle and perithyroid soft tissue is classified as T3 and further massive extension is classified as T4, the highest T grade. However, there have been few studies on the clinical significance of extension to the parathyroid gland in a large case series. In this study, we investigated the prognosis of PTC with extension to the parathyroid gland in a series of 3208 patients who underwent initial surgery between 1997 and 2004. Of these patients, 51 (1.6%) showed extension to the parathyroid gland on pathological examination. Twenty-one of these patients had massive extrathyroid extension to other adjacent organs corresponding to pT4. The remaining 30 were enrolled in this study. The disease-free survival (DFS) of these 30 patients was significantly better (p<0.0001) than that of pT4 patients and did not differ from that of patients showing minimal extrathyroid extension without extension to the parathyroid gland (p = 0.6264). Furthermore, none of these 30 patients died of carcinoma. Taken together, it is appropriate that extension to the parathyroid gland of PTC is graded as minimal extrathyroid extension (pT3), but not massive extension (pT4). Since minimal extension did not affect patient prognosis in our series, it is suggested that extension to the parathyroid gland has little clinical significance in PTC.

Multinodular goiter and primary hyperparathyroidism: a circuitous route to diagnosing metastatic uveal melanoma.

Uveal melanoma spreads exclusively via a hematogenous route and is notable for its latency. Liver metastases are common; however, metastatic spread to unusual sites has been encountered. We report the case of metastatic uveal melanoma in a woman with multinodular goiter and primary hyperparathyroidism. The patient presented with hypercalcemia and an elevated intact parathyroid hormone level, in conjunction with a follicular neoplasm in the setting of goiter. She underwent an uneventful total thyroidectomy and parathyroidectomy. Postoperatively, she became normocalcemic. Histopathologic analyses revealed metastatic uveal melanoma cells within both the multinodular goiter and parathyroid adenoma. At present, she is enrolled in a phase II trial for disseminated uveal melanoma. This is a report of uveal melanoma metastatic to both a parathyroid adenoma and a nodular hyperplastic thyroid. Additionally, this case serves to display the unusual metastatic potential of uveal melanoma.

Unusual case of metastatic neuroendocrine tumor.

OBJECTIVE: To report a rare case of metastatic growth hormone (GH)-secreting pituitary carcinoma causing acromegaly. METHODS: We present a case report and review the available literature on this topic. RESULTS: A 68-year-old woman presented with persistent acromegaly after treatment for a GH-secreting pituitary adenoma. Evaluation of long-standing cervical adenopathy revealed findings consistent with a metastatic neuroendocrine tumor. Further work-up revealed additional thyroid, parathyroid, and cervical masses. After operative treatment including total thyroidectomy, subtotal parathyroidectomy, partial thymectomy, and right modified radical neck dissection, the patient's symptoms diminished, and her GH levels approached the normal range. Surgical pathology findings were consistent with a GH-secreting pituitary carcinoma metastatic to the cervical lymph nodes, multinodular thyroid hyperplasia with a focus of papillary microcarcinoma, and parathyroid hyperplasia. CONCLUSION: Overall, pituitary carcinomas are extremely rare. To date, about 100 cases have been reported in the world's literature, and of these, only 19 cases originated from GH-secreting cells. Our examination of the symptoms, signs, diagnosis, and treatment of our patient, in comparison with the previously reported cases, should enhance awareness of this unusual disease process.

A case of parathyroid carcinoma with hypercalcemia responsive to cinacalcet therapy.

BACKGROUND: A 54-year-old man presented to the emergency department of his local hospital with a 1-year history of fatigue, weight loss, and constipation. He had abused alcohol for many years, and his symptoms were initially attributed to alcoholism. On physical examination, he was confused, his blood pressure was normal, he had no palpable neck masses, and his liver was enlarged. His serum calcium concentration was 4.2 mmol/l and his serum parathyroid hormone concentration was 36 pmol/l. CT-guided biopsy of a liver lesion showed large neoplastic cells, and fine-needle aspiration of the neck showed cells similar to those in the liver. The patient was treated with intravenous saline, pamidronate, and zoledronic acid. He was referred to our hospital on day 35 for treatment of refractory hypercalcemia. INVESTIGATIONS: Sestamibi parathyroid scan, chest and abdominal CT scans, neck ultrasonography, liver biopsy, fine-needle aspiration of neck mass, and measurement of parathyroid hormone in an aspirate of the neck mass. DIAGNOSIS: Primary hyperparathyroidism caused by metastatic parathyroid carcinoma. MANAGEMENT: Intravenous fluids, intravenous doses of pamidronate and zoledronic acid and oral cinacalcet therapy.

Development of tertiary hyperparathyroidism after phosphate supplementation in oncogenic osteomalacia.

Oncogenic osteomalacia is a rare paraneoplastic syndrome. It is characterized by bone pain, muscle weakness, gait disturbance, fractures and skeletal deformities. Hypophosphatemia, diminished renal phosphate reabsorption, decreased 1,25 dihydroxy Vitamin D and elevated alkaline phosphatase are the biochemical hallmarks of this disorder. Most tumors are of mesenchymal origin. We report the case of a 39-year-old woman with oncogenic osteomalacia caused by osteosarcoma of the right scapula which was unrecognized for several years. She subsequently developed tertiary hyperparathyroidism after treatment with oral phosphate and Vitamin D. This case illustrates that oncogenic osteomalacia may persist for many years before the tumor is discovered. This is because the tumors are frequently very small and are in obscure locations. The uniqueness of this case is the coexistence of hyperparathyroidism and oncogenic osteomalacia. Five other cases have been reported up to date. All patients had received phosphate supplement, ranging from 10 to 14 years prior to their diagnosis. Interestingly, our patient was on the treatment for only 2 years. The proposed mechanism is that exogenous phosphate stimulates parathyroid activity through sequestration of calcium.

Differential loss of heterozygosity in familial, sporadic, and uremic hyperparathyroidism.

Various genetic loci harboring oncogenes, tumor suppressor genes, and genes for calcium receptors have been implicated in the development of parathyroid tumors. We have carried out loss of heterozygosity (LOH) studies in chromosomes 1p, 1q, 3q, 6q, 11q, 13q, 15q, and X in a total of 89 benign parathyroid tumors. Of these, 28 were sporadic parathyroid adenomas from patients with no family history of the disease, 41 were secondary parathyroid tumors, 5 were from patients with a history of previous irradiation to the neck, 12 were from patients with a family history of hyperparathyroidism, and 3 were parathyroid tumors related to multiple endocrine neoplasia type 1 (MEN1). In addition, we determined the chromosomal localization of a second putative calcium-sensing receptor, CaS, for inclusion in the LOH studies. Based on analysis of somatic cell hybrids and fluorescent in situ hybridization to metaphase chromsomes, the gene for CaS was mapped to chromosomal region 2q21-q22. The following results were obtained from the LOH studies: (1) out of the 24 tumors that showed LOH, only 4 had more than one chromosomal region involved, (2) in the tumors from uremic patients, LOH of chromosome 3q was detected in a subset of the tumors, (3) LOH of the MEN1 region at 11q13 was the most common abnormality found in both MEN1-related and sporadic parathyroid tumours but was not a feature of the other forms of parathyroid tumors, (4) LOH in 1p and 6q was not as frequent as previously reported, and (5) tumor suppressor genes in 1q and X might have played a role, particularly on the X chromosome, in the case of familial parathyroid adenomas. We therefore conclude that the tumorigenesis of familial, sporadic, and uremic hyperparathyroidism involves different genetic triggers in a non-progressive pattern.