Mutinous Differentiation in Prostatic Adenocarcinoma JOHN E. McNEAL, MD, JOSEPH ALROY, DVM,” ARNAULD VILLERS, MD,t ELISE A. REDWINE, BS, FUAD S. FREIHA, MD, AND THOMAS A. STAMEY,
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among 2,800 prostatic resection specimens” confir-med the rarity of tumors meeting these histologic criteria. It is not clear from previous studies that this apparently rare combination of morphologic features and their unfavorable clinical implications constitutes a discrete biologic entity rather than the end of a continuum. Mucin secretion of lesser extent and in cancers of a variety of histologic patterns has been reported in at least one third of all prostatic adeno~carcinomas.‘~” Franks et al identified two mutinous adenocarcinomas (colloid cancers) in an autopsy series of 44 latent carcinomas and 50 clinical carcinomas: Histoc-hemically, they found the secretion of “colloid carcinoma” with mutinous lakes to be similar to that in mutinous cancel foci of lesser extent and other histologic patterns, and considered the designation of “colloid carcinoma” to be arbitrary. We have undertaken to document more thoroughly the full spectrum of histologic patterns associated with mucin secretion in prostatic carcinoma and to relate the volume and histologic features of the mutinous portion to the volume and histologic grade of the remainder of the tumor in a series of 100 radical prosta.tectomy specimens. Using histochemical, immunohistochemical, and lectin-binding stains, we have explored some of the biologic features of prostate cancer mucins and the cells that secrete them. Mucins are glycoproteins that are typically more than 50% carbohydrate, with a characteristic O-linkage of carbohydrate chains to a core protein that may COIItain up to 50% serine and threonine.7 They are highly viscous fluids and are secreted by epithelial cells to form a protective coating. Neutral mucins may jbe secreted in small amounts by prostate epithelial cells, whether benign or malignant, and are commonly present in cytoplasmic granules.‘,” They are variably eosinophilic and are stained by the periodic acid-Schiff tec‘hnique. which also stains most other types of carbohydrate-rich molecules of epithelial origin. ‘.’ Acidic mu&w are rare and scant in benign prostate gland lumens; their abundant secretion is specific for mutinous areas of prostate cancers.‘.’ They are variably (usually faintly) blasophilic with hematoxylin-eosin stain, but they are specifically identified by the alcian blue technique.“’ which does not stain neutral mucin or most other glycoproteins.’ Suifbmucins are acidic mucins that have terminal sulfate groups added to some of the carbohydralte chains and are alcian blue-positive at pH 2.5 or pH 1 .O. Sialomucins have terminal sialic acid groups added to at least some carbohydrate chains and are alcianophilic at pH 2.5, but not lower. Roth types of acidic mucins have been
Morphologic and histochemical analysis was performed on 33 carcinomas with mucin-secreting areas that were identified among 100 carcinomas from radical prostatectomy specimens. The most common mucin-secreting pattern was Gleason grade 3, which usually showed distinctive luminal distention, The “colloid carcinoma” pattern with mutinous lakes was the only histologic pattern that was unique to mutinous areas. Its frequent association with cribriform Gleason grade 4 carcinoma suggests that it is a variant of grade 4 cancer, whose deviant appearance is a consequence of mucus hypersecretion. Collagenous stromal micronodules, found in 13 cases, are a previously undescribed and distinctive pattern thought to be a stromal reaction to contact with acidic extraluminal mucin. In grade 3 carcinoma. glands that secreted into the stroma rather than the glansd lumen accounted for the stromal mucin, which appeared to lead to micronodule formation. In the grade 4 “colloid cancer” pattern, collagenous micronodules sometimes completely obliterated mutinous lakes, isolating residual cribriform glands in a “pseudo-grade 3” pattern. Lectin histochemical staining showed similar sialatcd and/or sulfated acidic mucin in all cases. Immunohistochemical staining showed downregulation of several differentiation antigens accompanying the alteration to mutinous differentiation. HLM PATHOI. 22:979-988. Copyright Q 1991 by W.B. Saunders Company
Mucincms adenocarcinoma of the prostate has generally been defined by the presence of lakes of extracellular mucin with embedded nests of neoplastic cells.‘” It has recently been proposed that this “colloid cancer” pattern should comprise at least 25% of the volume of anv cancer for it to be designated as “mutinous adenocarcinoma.“” In a recent study,? only six cases that fulfilled these criteria were identified in biopsy specimens from 1,600 prostatic carcinomas. All six were cancers of intermediate to high histologic grade; a cribriform pattern was dominant within the cellular islands embedded in the mutinous lakes in five of the six cancers. Clinically, these were all advanced tumors with a high rate of mortality; poor prognosis was also typical among 20
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among 2,800 prostatic resection specimens” confir-med the rarity of tumors meeting these histologic criteria. It is not clear from previous studies that this apparently rare combination of morphologic features and their unfavorable clinical implications constitutes a discrete biologic entity rather than the end of a continuum. Mucin secretion of lesser extent and in cancers of a variety of histologic patterns has been reported in at least one third of all prostatic adeno~carcinomas.‘~” Franks et al identified two mutinous adenocarcinomas (colloid cancers) in an autopsy series of 44 latent carcinomas and 50 clinical carcinomas: Histoc-hemically, they found the secretion of “colloid carcinoma” with mutinous lakes to be similar to that in mutinous cancel foci of lesser extent and other histologic patterns, and considered the designation of “colloid carcinoma” to be arbitrary. We have undertaken to document more thoroughly the full spectrum of histologic patterns associated with mucin secretion in prostatic carcinoma and to relate the volume and histologic features of the mutinous portion to the volume and histologic grade of the remainder of the tumor in a series of 100 radical prosta.tectomy specimens. Using histochemical, immunohistochemical, and lectin-binding stains, we have explored some of the biologic features of prostate cancer mucins and the cells that secrete them. Mucins are glycoproteins that are typically more than 50% carbohydrate, with a characteristic O-linkage of carbohydrate chains to a core protein that may COIItain up to 50% serine and threonine.7 They are highly viscous fluids and are secreted by epithelial cells to form a protective coating. Neutral mucins may jbe secreted in small amounts by prostate epithelial cells, whether benign or malignant, and are commonly present in cytoplasmic granules.‘,” They are variably eosinophilic and are stained by the periodic acid-Schiff tec‘hnique. which also stains most other types of carbohydrate-rich molecules of epithelial origin. ‘.’ Acidic mu&w are rare and scant in benign prostate gland lumens; their abundant secretion is specific for mutinous areas of prostate cancers.‘.’ They are variably (usually faintly) blasophilic with hematoxylin-eosin stain, but they are specifically identified by the alcian blue technique.“’ which does not stain neutral mucin or most other glycoproteins.’ Suifbmucins are acidic mucins that have terminal sulfate groups added to some of the carbohydralte chains and are alcian blue-positive at pH 2.5 or pH 1 .O. Sialomucins have terminal sialic acid groups added to at least some carbohydrate chains and are alcianophilic at pH 2.5, but not lower. Roth types of acidic mucins have been
Morphologic and histochemical analysis was performed on 33 carcinomas with mucin-secreting areas that were identified among 100 carcinomas from radical prostatectomy specimens. The most common mucin-secreting pattern was Gleason grade 3, which usually showed distinctive luminal distention, The “colloid carcinoma” pattern with mutinous lakes was the only histologic pattern that was unique to mutinous areas. Its frequent association with cribriform Gleason grade 4 carcinoma suggests that it is a variant of grade 4 cancer, whose deviant appearance is a consequence of mucus hypersecretion. Collagenous stromal micronodules, found in 13 cases, are a previously undescribed and distinctive pattern thought to be a stromal reaction to contact with acidic extraluminal mucin. In grade 3 carcinoma. glands that secreted into the stroma rather than the glansd lumen accounted for the stromal mucin, which appeared to lead to micronodule formation. In the grade 4 “colloid cancer” pattern, collagenous micronodules sometimes completely obliterated mutinous lakes, isolating residual cribriform glands in a “pseudo-grade 3” pattern. Lectin histochemical staining showed similar sialatcd and/or sulfated acidic mucin in all cases. Immunohistochemical staining showed downregulation of several differentiation antigens accompanying the alteration to mutinous differentiation. HLM PATHOI. 22:979-988. Copyright Q 1991 by W.B. Saunders Company
Mucincms adenocarcinoma of the prostate has generally been defined by the presence of lakes of extracellular mucin with embedded nests of neoplastic cells.‘” It has recently been proposed that this “colloid cancer” pattern should comprise at least 25% of the volume of anv cancer for it to be designated as “mutinous adenocarcinoma.“” In a recent study,? only six cases that fulfilled these criteria were identified in biopsy specimens from 1,600 prostatic carcinomas. All six were cancers of intermediate to high histologic grade; a cribriform pattern was dominant within the cellular islands embedded in the mutinous lakes in five of the six cancers. Clinically, these were all advanced tumors with a high rate of mortality; poor prognosis was also typical among 20
