{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:09Z","timestamp":1784557089037,"version":"3.55.0"},"reference-count":20,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eo.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:p>Parathyroid carcinoma (PC) is a rare endocrine malignancy. It accounts for about 1% of all primary hyperparathyroidism (PHPT) cases and 0.005% of all malignancies. PC presents with severe hypercalcemia, often refractory to standard medical treatment, which is crucial for improving patient outcomes. Differentiating PC from atypical parathyroid adenomas and parathyromatosis can be challenging. PC is diagnosed by angio-invasion, lymphatic and perineural invasion, and local malignant invasion with regional and distant metastasis. CD31 positivity on immunohistochemistry, indicating tumor cells within blood vessels in the pseudocapsule (vascular invasion), and a Ki-67% proliferative index of 8% confirm the diagnosis. We describe a 67-year-old man who presented with neck swelling, abdominal pain, and weight loss. Five years prior, he underwent a left inferior parathyroidectomy for a mass, which histological examination identified as clear cell parathyroid adenoma. Three years post-parathyroidectomy, he developed recurrent left-sided neck swelling. Magnetic resonance imaging revealed a lesion with mediastinal extension but no lymph node metastasis. During surgery, the lesion was adherent to the common carotid artery, and histopathological examination confirmed parathyromatosis. Recently, he presented again with new-onset neck swelling, abdominal pain, and weight loss. Biochemical investigations confirmed primary hyperparathyroidism. Invasive growth into surrounding tissues, blood vessels, and nerves, along with lymph node involvement and lung metastasis, with histopathology showing CD31 positivity and a Ki-67% proliferative index of 8%, confirmed the diagnosis of PC. As the tumor was inoperable, hypercalcemia was managed with cinacalcet, resulting in a decline in serum calcium levels.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Parathyroid carcinoma is one of the rarest malignancies.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Parathyromatosis is parathyroid tissue displaced in the neck and mediastinum due to prior surgery or aberrant embryonic development.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>The diagnosis of parathyroid carcinoma on histopathology is based on:<\/jats:p>\n                        <jats:list list-type=\"alpha-lower\">\n                          <jats:list-item>\n                            <jats:p>Local invasion into adjacent structures, such as adipose tissues\/skeletal muscle bundles.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Loco-regional invasion\u2013lymphatic (D240 IHC+), angio-invasion (CD31 IHC+), and perineural invasion.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Nuclear pleomorphism, hyperchromatic nuclei, and increased mitosis (high Ki-67 proliferative index of &gt;5%).<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Regional and distant metastasis in the lungs and other organs.<\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Management of severe hypercalcemia is crucial for improving patient outcomes.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/eo-25-0024","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T10:45:55Z","timestamp":1746528355000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-15","source":"Crossref","is-referenced-by-count":0,"title":["Malignant transformation of parathyromatosis to parathyroid carcinoma with invasive growth and distant metastasis"],"prefix":"10.1530","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-4053","authenticated-orcid":true,"given":"Chittari Venkata","family":"Harinarayan","sequence":"first","affiliation":[{"name":"Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sakra World Hospitals, Bangalore, Karnataka State, India"},{"name":"Department of Medicine & Endocrinology, Saveetha Institute of Medical and Technical Sciences University, Saveetha Medical College, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anugnya Premdas","family":"Ranjoalkar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sakra World Hospitals, Bangalore, Karnataka State, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha Sawkar","family":"Tandon","sequence":"additional","affiliation":[{"name":"Department of Radiology, Sakra World Hospitals, Bangalore, Karnataka State, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honey","family":"Ashok","sequence":"additional","affiliation":[{"name":"Department of ENT, Head and Neck Surgery, Sakra World Hospitals, Bangalore, Karnataka State, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu","family":"Prashant","sequence":"additional","affiliation":[{"name":"Interventional Radiology, Sakra World Hospitals, Bangalore, Karnataka State, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Front Oncol","article-title":"Treatment and outcome of metastatic parathyroid carcinoma: a systematic review and pooled analysis of published cases","volume":"12","author":"Alberti A","year":"2022","unstructured":"Alberti A\n, \nSmussi D\n, \nZamparini M\n, et al.\n 2022 Treatment and outcome of metastatic parathyroid carcinoma: a systematic review and pooled analysis of published cases. Front Oncol 12 997009. (https:\/\/doi.org\/10.3389\/fonc.2022.997009)"},{"key":"bib2","series-title":"Endocr Pathol","first-page":"113","article-title":"Immunohistochemistry in diagnostic parathyroid pathology","volume":"29","author":"Erickson LA","year":"2018","unstructured":"Erickson LA\n & \nMete O\n\n 2018 Immunohistochemistry in diagnostic parathyroid pathology. Endocr Pathol 29 113\u2013129. (https:\/\/doi.org\/10.1007\/s12022-018-9527-6)"},{"key":"bib3","series-title":"Endocr Pathol","first-page":"64","article-title":"Overview of the 2022 WHO classification of parathyroid tumors","volume":"33","author":"Erickson LA","year":"2022","unstructured":"Erickson LA\n, \nMete O\n, \nJuhlin CC\n, et al.\n 2022 Overview of the 2022 WHO classification of parathyroid tumors. Endocr Pathol 33 64\u201389. (https:\/\/doi.org\/10.1007\/s12022-022-09709-1)"},{"key":"bib4","series-title":"Metabolism","first-page":"762","article-title":"Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism","volume":"61","author":"Hage MP","year":"2012","unstructured":"Hage MP\n, \nSalti I\n & \nEl-Hajj FG\n\n 2012 Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism. Metabolism 61 762\u2013775. (https:\/\/doi.org\/10.1016\/j.metabol.2011.11.001)"},{"key":"bib5","series-title":"Endocr Pract","first-page":"189","article-title":"Parathyromatosis: a cause for recurrent hyperparathyroidism","volume":"7","author":"Lee PC","year":"2001","unstructured":"Lee PC\n, \nMateo RB\n, \nClarke MR\n, et al.\n 2001 Parathyromatosis: a cause for recurrent hyperparathyroidism. Endocr Pract 7 189\u2013192. (https:\/\/doi.org\/10.4158\/EP.7.3.189)"},{"key":"bib6","series-title":"Hematol Oncol Clin North Am","first-page":"1221","article-title":"Parathyroid carcinoma: challenges in diagnosis and treatment","volume":"26","author":"Mohebati A","year":"2012","unstructured":"Mohebati A\n, \nShaha A\n & \nShah J\n\n 2012 Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am 26 1221\u20131238. (https:\/\/doi.org\/10.1016\/j.hoc.2012.08.009)"},{"key":"bib7","series-title":"Front Endocrinol","article-title":"Denosumab for the treatment of hypercalcemia in a patient with parathyroid carcinoma: a case report","volume":"12","author":"Roukain A","year":"2022","unstructured":"Roukain A\n, \nAlwan H\n, \nBongiovanni M\n, et al.\n 2022 Denosumab for the treatment of hypercalcemia in a patient with parathyroid carcinoma: a case report. Front Endocrinol 12 794988. (https:\/\/doi.org\/10.3389\/fendo.2021.794988)"},{"key":"bib8","series-title":"Head Neck Pathol","first-page":"727","article-title":"Distinguishing parathyromatosis, atypical parathyroid adenomas, and parathyroid carcinomas utilizing histologic and clinical features","volume":"15","author":"Schulte JJ","year":"2021","unstructured":"Schulte JJ\n, \nPease G\n, \nTaxy JB\n, et al.\n 2021 Distinguishing parathyromatosis, atypical parathyroid adenomas, and parathyroid carcinomas utilizing histologic and clinical features. Head Neck Pathol 15 727\u2013736. (https:\/\/doi.org\/10.1007\/s12105-020-01281-6)"},{"key":"bib9","series-title":"J Clin Endocrinol Metab","first-page":"3803","article-title":"Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma","volume":"92","author":"Silverberg SJ","year":"2007","unstructured":"Silverberg SJ\n, \nRubin MR\n, \nFaiman C\n, et al.\n 2007 Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab 92 3803\u20133808. (https:\/\/doi.org\/10.1210\/jc.2007-0585)"},{"key":"bib10","series-title":"Int J Mol Sci","first-page":"6981","article-title":"Immunohistochemical profile of parathyroid tumours: a comprehensive review","volume":"23","author":"Uljanovs R","year":"2022","unstructured":"Uljanovs R\n, \nSinkarevs S\n, \nStrumfs B\n, et al.\n 2022 Immunohistochemical profile of parathyroid tumours: a comprehensive review. Int J Mol Sci 23 6981. (https:\/\/doi.org\/10.3390\/ijms23136981)"},{"key":"bib1","series-title":"Front Oncol","article-title":"Treatment and outcome of metastatic parathyroid carcinoma: a systematic review and pooled analysis of published cases","volume":"12","author":"Alberti A","year":"2022","unstructured":"Alberti A\n, \nSmussi D\n, \nZamparini M\n, et al.\n 2022 Treatment and outcome of metastatic parathyroid carcinoma: a systematic review and pooled analysis of published cases. Front Oncol 12 997009. (https:\/\/doi.org\/10.3389\/fonc.2022.997009)"},{"key":"bib2","series-title":"Endocr Pathol","first-page":"113","article-title":"Immunohistochemistry in diagnostic parathyroid pathology","volume":"29","author":"Erickson LA","year":"2018","unstructured":"Erickson LA\n & \nMete O\n\n 2018 Immunohistochemistry in diagnostic parathyroid pathology. Endocr Pathol 29 113\u2013129. (https:\/\/doi.org\/10.1007\/s12022-018-9527-6)"},{"key":"bib3","series-title":"Endocr Pathol","first-page":"64","article-title":"Overview of the 2022 WHO classification of parathyroid tumors","volume":"33","author":"Erickson LA","year":"2022","unstructured":"Erickson LA\n, \nMete O\n, \nJuhlin CC\n, et al.\n 2022 Overview of the 2022 WHO classification of parathyroid tumors. Endocr Pathol 33 64\u201389. (https:\/\/doi.org\/10.1007\/s12022-022-09709-1)"},{"key":"bib4","series-title":"Metabolism","first-page":"762","article-title":"Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism","volume":"61","author":"Hage MP","year":"2012","unstructured":"Hage MP\n, \nSalti I\n & \nEl-Hajj FG\n\n 2012 Parathyromatosis: a rare yet problematic etiology of recurrent and persistent hyperparathyroidism. Metabolism 61 762\u2013775. (https:\/\/doi.org\/10.1016\/j.metabol.2011.11.001)"},{"key":"bib5","series-title":"Endocr Pract","first-page":"189","article-title":"Parathyromatosis: a cause for recurrent hyperparathyroidism","volume":"7","author":"Lee PC","year":"2001","unstructured":"Lee PC\n, \nMateo RB\n, \nClarke MR\n, et al.\n 2001 Parathyromatosis: a cause for recurrent hyperparathyroidism. Endocr Pract 7 189\u2013192. (https:\/\/doi.org\/10.4158\/EP.7.3.189)"},{"key":"bib6","series-title":"Hematol Oncol Clin North Am","first-page":"1221","article-title":"Parathyroid carcinoma: challenges in diagnosis and treatment","volume":"26","author":"Mohebati A","year":"2012","unstructured":"Mohebati A\n, \nShaha A\n & \nShah J\n\n 2012 Parathyroid carcinoma: challenges in diagnosis and treatment. Hematol Oncol Clin North Am 26 1221\u20131238. (https:\/\/doi.org\/10.1016\/j.hoc.2012.08.009)"},{"key":"bib7","series-title":"Front Endocrinol","article-title":"Denosumab for the treatment of hypercalcemia in a patient with parathyroid carcinoma: a case report","volume":"12","author":"Roukain A","year":"2022","unstructured":"Roukain A\n, \nAlwan H\n, \nBongiovanni M\n, et al.\n 2022 Denosumab for the treatment of hypercalcemia in a patient with parathyroid carcinoma: a case report. Front Endocrinol 12 794988. (https:\/\/doi.org\/10.3389\/fendo.2021.794988)"},{"key":"bib8","series-title":"Head Neck Pathol","first-page":"727","article-title":"Distinguishing parathyromatosis, atypical parathyroid adenomas, and parathyroid carcinomas utilizing histologic and clinical features","volume":"15","author":"Schulte JJ","year":"2021","unstructured":"Schulte JJ\n, \nPease G\n, \nTaxy JB\n, et al.\n 2021 Distinguishing parathyromatosis, atypical parathyroid adenomas, and parathyroid carcinomas utilizing histologic and clinical features. Head Neck Pathol 15 727\u2013736. (https:\/\/doi.org\/10.1007\/s12105-020-01281-6)"},{"key":"bib9","series-title":"J Clin Endocrinol Metab","first-page":"3803","article-title":"Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma","volume":"92","author":"Silverberg SJ","year":"2007","unstructured":"Silverberg SJ\n, \nRubin MR\n, \nFaiman C\n, et al.\n 2007 Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab 92 3803\u20133808. (https:\/\/doi.org\/10.1210\/jc.2007-0585)"},{"key":"bib10","series-title":"Int J Mol Sci","first-page":"6981","article-title":"Immunohistochemical profile of parathyroid tumours: a comprehensive review","volume":"23","author":"Uljanovs R","year":"2022","unstructured":"Uljanovs R\n, \nSinkarevs S\n, \nStrumfs B\n, et al.\n 2022 Immunohistochemical profile of parathyroid tumours: a comprehensive review. Int J Mol Sci 23 6981. (https:\/\/doi.org\/10.3390\/ijms23136981)"}],"container-title":["Endocrine Oncology"],"original-title":[],"link":[{"URL":"https:\/\/eo.bioscientifica.com\/view\/journals\/eo\/5\/1\/EO-25-0024.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eo.bioscientifica.com\/downloadpdf\/journals\/eo\/5\/1\/EO-25-0024.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/eo.bioscientifica.com\/downloadpdf\/journals\/eo\/5\/1\/EO-25-0024.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:50:34Z","timestamp":1784555434000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/eo\/article\/34508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":20,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/eo-25-0024","relation":{},"ISSN":["2634-4793"],"issn-type":[{"value":"2634-4793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}