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Hyalinizing parathyroid adenoma and hyperplasia: report of 3 cases of an unusual histologic variant
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Annals of Diagnostic Pathology 15 (2011) 329 – 332
Hyalinizing parathyroid adenoma and hyperplasia: report of 3 cases of an unusual histologic variant Maha Elgoweini, MB, ChB, MSc, MD, Runjan Chetty, MB, BCh, FRCPath, DPhil⁎ Department of Pathology, Western Infirmary and University of Glasgow, Glasgow, United Kingdom
Abstract
Keywords:
Fibrosis in the parathyroid glands can be seen in adenomas, in carcinomas, and after fine needle aspiration of the thyroid gland. Fibrosis occurs in approximately 10% of typical adenomas and in all atypical adenomas. This is usually in the form of fibrous bands or trabeculae that intersect the hypercellular parenchyma. However, widespread diffuse fibrosis or sclerosis in either parathyroid gland hyperplasia or adenoma has not been reported before in the English medical literature. We report 3 cases of hyperparathyroidism (2 adenomas and 1 hyperplasia) with an unusual pattern of sclerosis. The hyalinized, eosinophilic fibrous tissue was diffusely distributed within and around the parathyroid parenchyma, often isolating groups of cells and single cells. © 2011 Elsevier Inc. All rights reserved. Parathyroid adenoma; Parathyroid hyperplasia; Diffuse sclerosis; Parathyroid hyalinization
1. Introduction Histologic examination of parathyroid gland is usually requested when a hyperfunctioning gland or glands are surgically removed to treat hyperparathyroidism. The histologic changes, irrespective of the cause of the hyperparathyroidism, are of a hypercellular lesion [1]. Degenerative changes can be seen in adenomas and carcinomas; these are usually because of hemorrhage, cyst formation, or even necrosis [2]. In addition, degenerative changes may occur in the parathyroid glands after fine needle aspiration (FNA) of the thyroid gland [3]. Fibrosis occurs in approximately 10% of typical adenomas and, by definition, in all “atypical” adenomas. This is usually in the form of fibrous bands or trabeculae that intersect the hypercellular parenchyma [2]. However, widespread diffuse fibrosis or sclerosis in parathyroid gland either with hyperplasia or with adenoma has not been reported before in the English medical literature. We report 3 cases of hyperparathyroidism (2 adenomas and 1 hyperplasia) with an unusual pattern of sclerosis where individual cells and small groups of cells ⁎ Corresponding author. Department of Cellular Pathology, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. E-mail address: [email protected] (R. Chetty). 1092-9134/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2011.03.001
were surrounded and suspended within a paucicellular, hyalinized stroma.
2. Case histories 2.1. Case 1 An 85-year-old woman presented with primary hyperparathyroidism. The serum parathyroid hormone (PTH) level was 53.3 pmol/L (normal levels, 1.6-7.5 pmol/L), and the adjusted serum calcium level was 3.03 mmol/L (normal levels, 2.1-2.6 mmol/L). She had a neck exploration, and a right inferior parathyroidectomy was performed. The postoperative calcium levels decreased to normal levels a day later. 2.2. Case 2 A 36-year-old woman with a background of renal failure owing to chronic pyelonephritis for which she had a cadaveric renal transplant presented with uncontrolled hyperparathyroidism unresponsive to cinacalcet. The serum PTH level was 147.4 pmol/L, and the adjusted serum calcium was 2.63 mmol/L. She underwent a neck exploration with left superior and inferior and right superior parathyroidectomies. The calcium level returned to normal levels the
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M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
following day. Her PTH levels 2 months after the operation was 9.9 pmol/L. 2.3. Case 3 A 43-year-old man presented with a lump in his right neck and complained of weight loss, nausea, and vomiting. Imaging localized the lump to the right upper parathyroid gland. His serum PTH was 124.6 pmol/L, and the adjusted serum calcium was 3.11 mmol/L. The right superior parathyroid gland was removed. Postoperatively, the calcium levels returned to normal together with cessation of his symptoms. None of the patients had preoperative FNA biopsies or any other form of manipulation that may have resulted in trauma to the parathyroid glands. 3. Materials and methods All specimens were received in 10% neutral buffered formalin and were grossed and processed routinely. All specimens were weighed, measured, inked, and submitted in total. Routine hematoxylin and eosin sections were generated. Congo red stain, immunohistochemistry, and ultrastructural examination for amyloid were performed. 4. Gross pathology 4.1. Case 1 On gross examination of the gland, it weighed 5.7 g, and on sectioning, it had a firm yellow cut surface that was partly cystic. 4.2. Case 2 The 4 submitted parathyroid glands (left superior and inferior, and right superior and inferior) weighed 0.27, 0.31, 0.44, and 0.34 g, respectively. No remarkable gross features were apparent. 4.3. Case 3 The parathyroid gland weighed 5.2 g; was of firm, rubbery consistency; and had a homogenous yellow-brown cut surface. 5. Microscopy The specimen submitted as the right inferior parathyroid gland proved to be a lymph node on microscopy. All other confirmed parathyroid glands showed benign, cellular lesions. The parenchyma was cellular with a predominance of water-clear cells and occasional oncocytes. There was no cytologic atypia, extension into adjacent fat, mitotic activity, vascular invasion, or necrosis. The lesions from cases 1 and 3 were encapsulated, and both contained
compressed, peripheral, normal-appearing parathyroid tissue (Fig. 1A and B). Both lesions qualified as parathyroid adenomas clinically and pathologically. The 3 parathyroid glands from case 2 were also cellular lesions with focal cystic change but were not encapsulated (Fig. 1C). Peripheral normal parathyroid tissue was not seen, and the clinicopathologic features were in keeping with parathyroid hyperplasia. Only the right superior parathyroid gland showed sclerosis. The most striking histologic feature was the extensive, permeative stromal sclerosis seen in the 3 affected parathyroid glands (Fig. 2). The entire lesion contained the eosinophilic, hyalinized, paucicellular fibrous tissue, although the more central parts were less affected than the periphery of lesions. The amorphous fibrous tissue surrounded and invested small groups of cells as well as individual cells appeared entrapped (Fig. 3). Focally, the entrapped parenchyma appeared slightly atrophic. The histologic appearance raised the possibility of amyloid deposition; however, Congo red stains did not reveal apple green birefringence; immunohistochemistry and ultrastructural examination for amyloid was negative.
6. Discussion Fibrous tissue is encountered within an adenomatous or hyperplastic parathyroid gland occasionally and is usually a focal occurrence. It is usually delicate and may or may not be associated with hemorrhage and necrosis [4]. Particular importance is attached to the fibrosis if it is present as thick fibrous trabeculae or bands coursing through the hypercellular parenchyma [5]. This raises the histologic differential diagnosis of an atypical adenoma or indeed a parathyroid carcinoma. In this setting, the fibrous bands extend from the capsule into the hypercellular parenchyma dividing it into incompletely formed lobules [2,4]. The diagnosis of parathyroid cancer is not based solely on the presence of fibrous bands, but they are also accompanied by an increased mitotic count and Ki-67 index, sometimes necrosis, capsular and/or vascular invasion, and extraparathyroid extension [1]. Similarly, atypical parathyroid adenomas may contain broad fibrous bands similar to that encountered in carcinoma but lack unequivocal features of malignancy such as capsular and/or vascular invasion, extraparathyroid spread, and evidence of metastatic disease [2]. Another potential cause for extensive fibrosis is FNA of the thyroid gland in the investigation of lumps or masses in this location. Alwaheeb et al [3] reported so-called worrisome histologic alterations after fine needle aspiration of the parathyroid, with microscopic changes reminiscent of those encountered in the thyroid after the same procedure. The parathyroid gland showed dense fibrosis extending from the capsule into parathyroid parenchyma. The fibrosis was accompanied by calcification, fresh hemorrhage, and hemosiderin-laden macrophages [3].
M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
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Fig. 2. All 3 parathyroid glands had a similar appearance. There was diffuse stromal sclerosis characterized by acellular, eosinophilic fibrous tissue that surrounded the parenchymal component. (hematoxylin and eosin, original magnification ×100).
tissue with a vascular proliferation, hemosiderin-laden macrophages, and other histologic stigmata of antecedent FNA biopsy were lacking. Amyloid deposits in normal, hyperplastic, and adenomatous parathyroid glands have been localized to 2 areas: within parathyroid follicles and the “interstitium,” which is presumed to be the stroma [6]. The parathyroid may be “secondarily” involved in amyloidosis affecting the thyroid gland [7,8]. Intratumoral sclerosis similar to what we describe in the parathyroid has been encountered in other endocrine tumors, most notably paragangliomas [9]. Importantly, the pattern of fibrosis or sclerosis that we highlight in these 3 cases is different from that encountered in atypical parathyroid adenoma, in parathyroid carcinoma,
Fig. 1. (A-C) Scanning magnifications illustrating the sclerosing parathyroid adenomas (A and B), and the hyperplastic parathyroid gland from case 2 (C).
The cases that we describe herein did not have concomitant thyroid pathology, and none of the patients had FNA biopsies. In addition, hemorrhage, granulation
Fig. 3. The hyalinized stroma surrounded groups as well as individual waterclear parathyroid cells (hematoxylin and eosin, original magnification ×400).
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M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
and after FNA biopsy. The diffuse nature, envelopment of small clusters of cells, and extension around single cells make it an unusual and rare form of fibrosis within adenomatous and hyperplastic glands. Although the cause is unknown, this probably represents an exaggerated stromal response and is similar to other lesions and tumors that are characterized by stromal hyalinization. As far as we can ascertain, there does not appear to be any biologic significance to the presence of such diffuse sclerosis. The purposes of this report are to highlight an unusual and rare pattern of sclerosis encountered in parathyroid hyperplasia and adenoma and to distinguish it from the pattern of fibrosis associated with atypical parathyroid adenomas and parathyroid carcinoma. References [1] Johnson SJ. Changing clinicopathological practice in parathyroid disease. Histopathology 2010;56:835-51.
[2] Stojadinovic A, Hoos A, Nissan A, Dudas ME, Cordon-Cardo C, Shaha AR, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol 2003;34:54-64. [3] Alwaheeb S, Rambaldini G, Boerner S, Coire' C, Fiser J, Asa SL. Worrisome histologic alterations following fine-needle aspiration of the parathyroid. J Clin Pathol 2006;59:1094-6. [4] Wieneke JA, Smith A. Parathyroid adenoma. Head Neck Pathol 2008;2: 305-8. [5] Ghandur- Mnaymneh L, Kimura N. The parathyroid adenoma. A histopathologic definition with a study of 172 cases of primary hyperparathyroidism. Am J Pathol 1984;115:70-83. [6] Anderson TJ, Ewen SWB. Amyloid in normal and pathological parathyroid glands. J Clin Pathol 1974;27:656-63. [7] Villamil CF, Massimi G, D'Avella J, Cole SR. Amyloid goiter with parathyroid involvement: case report and review of the literature. Arch Pathol Lab Med 2000;124:281-3. [8] Abdou AG, Kandil MA. A case of amyloid goiter associated with intrathyroid parathyroid and lymphoepithelial cyst. Endocr Pathol 2009;20:243-8. [9] Plaza JA, Wakely Jr PE, Moran C, Fletcher CD, Suster S. Sclerosing paraganglioma: report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm. Am J Surg Pathol 2006;30:7-12.
Annals of Diagnostic Pathology 15 (2011) 329 – 332
Hyalinizing parathyroid adenoma and hyperplasia: report of 3 cases of an unusual histologic variant Maha Elgoweini, MB, ChB, MSc, MD, Runjan Chetty, MB, BCh, FRCPath, DPhil⁎ Department of Pathology, Western Infirmary and University of Glasgow, Glasgow, United Kingdom
Abstract
Keywords:
Fibrosis in the parathyroid glands can be seen in adenomas, in carcinomas, and after fine needle aspiration of the thyroid gland. Fibrosis occurs in approximately 10% of typical adenomas and in all atypical adenomas. This is usually in the form of fibrous bands or trabeculae that intersect the hypercellular parenchyma. However, widespread diffuse fibrosis or sclerosis in either parathyroid gland hyperplasia or adenoma has not been reported before in the English medical literature. We report 3 cases of hyperparathyroidism (2 adenomas and 1 hyperplasia) with an unusual pattern of sclerosis. The hyalinized, eosinophilic fibrous tissue was diffusely distributed within and around the parathyroid parenchyma, often isolating groups of cells and single cells. © 2011 Elsevier Inc. All rights reserved. Parathyroid adenoma; Parathyroid hyperplasia; Diffuse sclerosis; Parathyroid hyalinization
1. Introduction Histologic examination of parathyroid gland is usually requested when a hyperfunctioning gland or glands are surgically removed to treat hyperparathyroidism. The histologic changes, irrespective of the cause of the hyperparathyroidism, are of a hypercellular lesion [1]. Degenerative changes can be seen in adenomas and carcinomas; these are usually because of hemorrhage, cyst formation, or even necrosis [2]. In addition, degenerative changes may occur in the parathyroid glands after fine needle aspiration (FNA) of the thyroid gland [3]. Fibrosis occurs in approximately 10% of typical adenomas and, by definition, in all “atypical” adenomas. This is usually in the form of fibrous bands or trabeculae that intersect the hypercellular parenchyma [2]. However, widespread diffuse fibrosis or sclerosis in parathyroid gland either with hyperplasia or with adenoma has not been reported before in the English medical literature. We report 3 cases of hyperparathyroidism (2 adenomas and 1 hyperplasia) with an unusual pattern of sclerosis where individual cells and small groups of cells ⁎ Corresponding author. Department of Cellular Pathology, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. E-mail address: [email protected] (R. Chetty). 1092-9134/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2011.03.001
were surrounded and suspended within a paucicellular, hyalinized stroma.
2. Case histories 2.1. Case 1 An 85-year-old woman presented with primary hyperparathyroidism. The serum parathyroid hormone (PTH) level was 53.3 pmol/L (normal levels, 1.6-7.5 pmol/L), and the adjusted serum calcium level was 3.03 mmol/L (normal levels, 2.1-2.6 mmol/L). She had a neck exploration, and a right inferior parathyroidectomy was performed. The postoperative calcium levels decreased to normal levels a day later. 2.2. Case 2 A 36-year-old woman with a background of renal failure owing to chronic pyelonephritis for which she had a cadaveric renal transplant presented with uncontrolled hyperparathyroidism unresponsive to cinacalcet. The serum PTH level was 147.4 pmol/L, and the adjusted serum calcium was 2.63 mmol/L. She underwent a neck exploration with left superior and inferior and right superior parathyroidectomies. The calcium level returned to normal levels the
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M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
following day. Her PTH levels 2 months after the operation was 9.9 pmol/L. 2.3. Case 3 A 43-year-old man presented with a lump in his right neck and complained of weight loss, nausea, and vomiting. Imaging localized the lump to the right upper parathyroid gland. His serum PTH was 124.6 pmol/L, and the adjusted serum calcium was 3.11 mmol/L. The right superior parathyroid gland was removed. Postoperatively, the calcium levels returned to normal together with cessation of his symptoms. None of the patients had preoperative FNA biopsies or any other form of manipulation that may have resulted in trauma to the parathyroid glands. 3. Materials and methods All specimens were received in 10% neutral buffered formalin and were grossed and processed routinely. All specimens were weighed, measured, inked, and submitted in total. Routine hematoxylin and eosin sections were generated. Congo red stain, immunohistochemistry, and ultrastructural examination for amyloid were performed. 4. Gross pathology 4.1. Case 1 On gross examination of the gland, it weighed 5.7 g, and on sectioning, it had a firm yellow cut surface that was partly cystic. 4.2. Case 2 The 4 submitted parathyroid glands (left superior and inferior, and right superior and inferior) weighed 0.27, 0.31, 0.44, and 0.34 g, respectively. No remarkable gross features were apparent. 4.3. Case 3 The parathyroid gland weighed 5.2 g; was of firm, rubbery consistency; and had a homogenous yellow-brown cut surface. 5. Microscopy The specimen submitted as the right inferior parathyroid gland proved to be a lymph node on microscopy. All other confirmed parathyroid glands showed benign, cellular lesions. The parenchyma was cellular with a predominance of water-clear cells and occasional oncocytes. There was no cytologic atypia, extension into adjacent fat, mitotic activity, vascular invasion, or necrosis. The lesions from cases 1 and 3 were encapsulated, and both contained
compressed, peripheral, normal-appearing parathyroid tissue (Fig. 1A and B). Both lesions qualified as parathyroid adenomas clinically and pathologically. The 3 parathyroid glands from case 2 were also cellular lesions with focal cystic change but were not encapsulated (Fig. 1C). Peripheral normal parathyroid tissue was not seen, and the clinicopathologic features were in keeping with parathyroid hyperplasia. Only the right superior parathyroid gland showed sclerosis. The most striking histologic feature was the extensive, permeative stromal sclerosis seen in the 3 affected parathyroid glands (Fig. 2). The entire lesion contained the eosinophilic, hyalinized, paucicellular fibrous tissue, although the more central parts were less affected than the periphery of lesions. The amorphous fibrous tissue surrounded and invested small groups of cells as well as individual cells appeared entrapped (Fig. 3). Focally, the entrapped parenchyma appeared slightly atrophic. The histologic appearance raised the possibility of amyloid deposition; however, Congo red stains did not reveal apple green birefringence; immunohistochemistry and ultrastructural examination for amyloid was negative.
6. Discussion Fibrous tissue is encountered within an adenomatous or hyperplastic parathyroid gland occasionally and is usually a focal occurrence. It is usually delicate and may or may not be associated with hemorrhage and necrosis [4]. Particular importance is attached to the fibrosis if it is present as thick fibrous trabeculae or bands coursing through the hypercellular parenchyma [5]. This raises the histologic differential diagnosis of an atypical adenoma or indeed a parathyroid carcinoma. In this setting, the fibrous bands extend from the capsule into the hypercellular parenchyma dividing it into incompletely formed lobules [2,4]. The diagnosis of parathyroid cancer is not based solely on the presence of fibrous bands, but they are also accompanied by an increased mitotic count and Ki-67 index, sometimes necrosis, capsular and/or vascular invasion, and extraparathyroid extension [1]. Similarly, atypical parathyroid adenomas may contain broad fibrous bands similar to that encountered in carcinoma but lack unequivocal features of malignancy such as capsular and/or vascular invasion, extraparathyroid spread, and evidence of metastatic disease [2]. Another potential cause for extensive fibrosis is FNA of the thyroid gland in the investigation of lumps or masses in this location. Alwaheeb et al [3] reported so-called worrisome histologic alterations after fine needle aspiration of the parathyroid, with microscopic changes reminiscent of those encountered in the thyroid after the same procedure. The parathyroid gland showed dense fibrosis extending from the capsule into parathyroid parenchyma. The fibrosis was accompanied by calcification, fresh hemorrhage, and hemosiderin-laden macrophages [3].
M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
331
Fig. 2. All 3 parathyroid glands had a similar appearance. There was diffuse stromal sclerosis characterized by acellular, eosinophilic fibrous tissue that surrounded the parenchymal component. (hematoxylin and eosin, original magnification ×100).
tissue with a vascular proliferation, hemosiderin-laden macrophages, and other histologic stigmata of antecedent FNA biopsy were lacking. Amyloid deposits in normal, hyperplastic, and adenomatous parathyroid glands have been localized to 2 areas: within parathyroid follicles and the “interstitium,” which is presumed to be the stroma [6]. The parathyroid may be “secondarily” involved in amyloidosis affecting the thyroid gland [7,8]. Intratumoral sclerosis similar to what we describe in the parathyroid has been encountered in other endocrine tumors, most notably paragangliomas [9]. Importantly, the pattern of fibrosis or sclerosis that we highlight in these 3 cases is different from that encountered in atypical parathyroid adenoma, in parathyroid carcinoma,
Fig. 1. (A-C) Scanning magnifications illustrating the sclerosing parathyroid adenomas (A and B), and the hyperplastic parathyroid gland from case 2 (C).
The cases that we describe herein did not have concomitant thyroid pathology, and none of the patients had FNA biopsies. In addition, hemorrhage, granulation
Fig. 3. The hyalinized stroma surrounded groups as well as individual waterclear parathyroid cells (hematoxylin and eosin, original magnification ×400).
332
M. Elgoweini, R. Chetty / Annals of Diagnostic Pathology 15 (2011) 329–332
and after FNA biopsy. The diffuse nature, envelopment of small clusters of cells, and extension around single cells make it an unusual and rare form of fibrosis within adenomatous and hyperplastic glands. Although the cause is unknown, this probably represents an exaggerated stromal response and is similar to other lesions and tumors that are characterized by stromal hyalinization. As far as we can ascertain, there does not appear to be any biologic significance to the presence of such diffuse sclerosis. The purposes of this report are to highlight an unusual and rare pattern of sclerosis encountered in parathyroid hyperplasia and adenoma and to distinguish it from the pattern of fibrosis associated with atypical parathyroid adenomas and parathyroid carcinoma. References [1] Johnson SJ. Changing clinicopathological practice in parathyroid disease. Histopathology 2010;56:835-51.
[2] Stojadinovic A, Hoos A, Nissan A, Dudas ME, Cordon-Cardo C, Shaha AR, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol 2003;34:54-64. [3] Alwaheeb S, Rambaldini G, Boerner S, Coire' C, Fiser J, Asa SL. Worrisome histologic alterations following fine-needle aspiration of the parathyroid. J Clin Pathol 2006;59:1094-6. [4] Wieneke JA, Smith A. Parathyroid adenoma. Head Neck Pathol 2008;2: 305-8. [5] Ghandur- Mnaymneh L, Kimura N. The parathyroid adenoma. A histopathologic definition with a study of 172 cases of primary hyperparathyroidism. Am J Pathol 1984;115:70-83. [6] Anderson TJ, Ewen SWB. Amyloid in normal and pathological parathyroid glands. J Clin Pathol 1974;27:656-63. [7] Villamil CF, Massimi G, D'Avella J, Cole SR. Amyloid goiter with parathyroid involvement: case report and review of the literature. Arch Pathol Lab Med 2000;124:281-3. [8] Abdou AG, Kandil MA. A case of amyloid goiter associated with intrathyroid parathyroid and lymphoepithelial cyst. Endocr Pathol 2009;20:243-8. [9] Plaza JA, Wakely Jr PE, Moran C, Fletcher CD, Suster S. Sclerosing paraganglioma: report of 19 cases of an unusual variant of neuroendocrine tumor that may be mistaken for an aggressive malignant neoplasm. Am J Surg Pathol 2006;30:7-12.