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Cyclin D1

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 15 July 2013, last major update March 2013
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.


● Also called bcl1 - b cell lymphoma #1
● Coded by BCL1 / PRAD1 (parathyroid adenoma 1) gene on #11q13
● Responsible for transition to S phase by phosphorylating the retinoblastoma gene product, which releases transcription factors to initiate DNA replication
● Overexpression promotes transformation to a malignant phenotype; overexpressed in many tumors
● Cyclin D1 genotypes may be associated with nasopharyngeal carcinoma risk (Anticancer Res 2012;32:1093)

Uses by pathologists

Interpretation: nuclear stain
Mantle cell lymphoma: characterized by t(11;14) translocation, which places the cyclin D1 gene next to an immunoglobulin heavy chain enhancer gene; among lymphomas, cyclin D1 expression is very specific for mantle cell lymphoma; however, blastoid cases may be negative (Am J Surg Pathol 2012;36:214)
Parathyroid: overexpressed in 40% of parathyroid adenomas, strong staining in carcinomas

Micro images

Ampulla of Vater-carcinoma

Bone: giant cell tumor

Breast: MALT lymphoma is cyclin D1 negative

Breast: papilloma and papillary carcinoma

Cervix: various benign and malignant lesions

Mantle cell lympoma (small bowel)

Mantle cell lympoma (axillary lymph node)

Skin: normal

Skin: compound Spitz nevus and melanoma

Squamous cell carcinoma

Stomach: gastric or gastroesophageal junction adenocarcinoma

Uterus: normal, complex hyperplasia and carcinoma

Various images

Virtual slides

Breast: papilloma and papillary carcinoma

Mantle cell lymphoma

Molecular images

FISH in mantle cell lymphoma: cyclin D1/IgH single and double-fusion-positive cells in peripheral blood sample showing mantle cell lymphoma involvement

FISH in mantle cell lymphoma - blastoid variant

Positive staining - normal

● Endocervix (Mod Pathol 2010;23:611)
● Uterus: cycling endometrium

Positive staining - disease

Positive staining is nuclear staining:
● B-CLL (13%, Am J Surg Pathol 2004;28:801)
● Diffuse large B cell lymphoma (rare, Hum Pathol 2011;42:1204)
● Soft tissue: chondroid lipoma, Gardner type fibroma
Hairy cell leukemia (25%)
Inflammatory fibroid polyp
● Liver: Hepatoblastoma (some)
Mantle cell lymphoma
Myeloma (40%)
Pancreas: solid pseudopapillary tumor
Parathyroid adenoma (40%) and carcinoma (90%)
● Salivary gland: adenoid cystic carcinoma
● Splenic lymphoma with villous lymphocytes (10%)
● Uterus: endometrial stromal sarcoma-undifferentiated (Mod Pathol 2010;23:225, Am J Surg Pathol 2012;36:1562)
● Various carcinomas (Hum Pathol 2012;43:1386, Hum Pathol 2012;43:1044) and melanoma

Negative staining

Follicular lymphoma, marginal zone / MALT lymphoma
● Salivary gland: polymorphous low grade adenocarcinoma

End of Stains > Cyclin D1

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