Physiologic versus neoplastic C-cell hyperplasia of the thyroid: Separation of distinct histologic and biologic entities

Arrie Perry, Kyle Molberg, Jorge Albores-Saavedra

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

BACKGROUND. Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together trader the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS. In order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100x). Hematoxylin and eosin (H and E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS. Physiologic or reactive CCH was not recognized with certainty on H and E stains in any of the cases due to morphologic similarities between C- cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H and E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET protooncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS. Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can he identified with H and E stained sections. Consequently, the number of C cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor [medullary carcinoma in situ) of invasive medullary carcinoma.

Original languageEnglish (US)
Pages (from-to)750-756
Number of pages7
JournalCancer
Volume77
Issue number4
DOIs
StatePublished - Feb 15 1996

Fingerprint

Hyperplasia
Thyroid Gland
Hematoxylin
Eosine Yellowish-(YS)
Calcitonin
Coloring Agents
Medullary Carcinoma
Carcinoma in Situ
Thyroidectomy
Basement Membrane

Keywords

  • familial medullary carcinoma
  • immunohistochemistry
  • medullary carcinoma in situ
  • MEN IIa
  • MEN IIb
  • physiologic C-cell hyperplasia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Physiologic versus neoplastic C-cell hyperplasia of the thyroid : Separation of distinct histologic and biologic entities. / Perry, Arrie; Molberg, Kyle; Albores-Saavedra, Jorge.

In: Cancer, Vol. 77, No. 4, 15.02.1996, p. 750-756.

Research output: Contribution to journalArticle

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title = "Physiologic versus neoplastic C-cell hyperplasia of the thyroid: Separation of distinct histologic and biologic entities",
abstract = "BACKGROUND. Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together trader the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS. In order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100x). Hematoxylin and eosin (H and E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS. Physiologic or reactive CCH was not recognized with certainty on H and E stains in any of the cases due to morphologic similarities between C- cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H and E stains at the periphery of 11/12 (92{\%}) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET protooncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS. Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can he identified with H and E stained sections. Consequently, the number of C cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor [medullary carcinoma in situ) of invasive medullary carcinoma.",
keywords = "familial medullary carcinoma, immunohistochemistry, medullary carcinoma in situ, MEN IIa, MEN IIb, physiologic C-cell hyperplasia",
author = "Arrie Perry and Kyle Molberg and Jorge Albores-Saavedra",
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T2 - Separation of distinct histologic and biologic entities

AU - Perry, Arrie

AU - Molberg, Kyle

AU - Albores-Saavedra, Jorge

PY - 1996/2/15

Y1 - 1996/2/15

N2 - BACKGROUND. Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together trader the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS. In order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100x). Hematoxylin and eosin (H and E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS. Physiologic or reactive CCH was not recognized with certainty on H and E stains in any of the cases due to morphologic similarities between C- cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H and E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET protooncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS. Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can he identified with H and E stained sections. Consequently, the number of C cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor [medullary carcinoma in situ) of invasive medullary carcinoma.

AB - BACKGROUND. Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together trader the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists. METHODS. In order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100x). Hematoxylin and eosin (H and E) stained sections and immunohistochemical stains for calcitonin were assessed in each case. RESULTS. Physiologic or reactive CCH was not recognized with certainty on H and E stains in any of the cases due to morphologic similarities between C- cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H and E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET protooncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells. CONCLUSIONS. Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can he identified with H and E stained sections. Consequently, the number of C cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor [medullary carcinoma in situ) of invasive medullary carcinoma.

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KW - MEN IIb

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