AJCP / Case Report
Multifocal Mantle Cell Lymphoma In Situ in the Setting of a Composite Lymphoma Caroline Sloan,1 Qun-Bin Xiong, MD,1 Anne Crivaro, PhD,1 Sharon Steinman, MD,2 and Adam Bagg, MD1 From the 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, and 2St Luke’s Hospital at St Luke’s University Health Network, Allentown, PA. Key Words: Composite lymphoma; Mantle cell lymphoma in situ; Marginal zone lymphoma Am J Clin Pathol February 2015;143:274-282 DOI: 10.1309/AJCP06VIKFMTRCXD
ABSTRACT Objectives: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically defined but histologically inapparent neoplastic cells restricted to narrow mantle zones, without expansion or invasion beyond the mantle zone. We report a unique case of MCLIS associated with a much more manifest nodal marginal zone lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone marrow. Methods: Biopsies from all three locations were evaluated using standard H&E-stained sections, immunohistochemistry, flow cytometry, metaphase cytogenetics, and/or fluorescence in situ hybridization (FISH). Results: This case is unique for three reasons. First, the histologically covert mantle cell lymphoma was multifocal, detected in all three locations using one or more of flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS was always accompanied by a more histologically dominant MZL. Third, where evaluable, it did not grow in an appreciable mantle zone distribution, presumably due to destruction of the normal nodal architecture by the neoplastic MZL cells and the resulting absence of recognizable follicles and mantle zones. Conclusions: This unique case provides new insight into the pathogenesis of MCLIS.
274 Am J Clin Pathol 2015;143:274-282 DOI: 10.1309/AJCP06VIKFMTRCXD
Upon completion of this activity you will be able to: • describe the immunophenotype and hallmark translocation associated with mantle cell lymphoma. • define the features of mantle cell lymphoma in situ (MCLIS). • discuss the clinical implications of a diagnosis of MCLIS. • define potential early precursors of lymphoid neoplasms. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 307. Exam is located at www.ascp.org/ajcpcme.
In the past two decades, a number of case reports and case series have been published describing follicular lymphomas (FLs) and mantle cell lymphomas (MCLs) with “in situ” growth patterns.1 In 2008, the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues recognized these lesions as containing neoplastic cells that accumulate in the location normally occupied by their benign counterparts but are histologically and morphologically inapparent.1 In FL in situ (FLIS), also referred to as in situ FL-like B cells of uncertain significance, neoplastic cells accumulate within the germinal centers of secondary lymphoid follicles of otherwise reactive lymph nodes.2 In MCL in situ (MCLIS), also termed in situ MCL-like B cells of uncertain significance, neoplastic cells are almost exclusively restricted to the inner mantle zone or narrow mantles, without expansion of the mantle zone or invasion beyond the mantle zone.3 Occasionally, it may be difficult to distinguish between MCLIS and early involvement of overt MCL, in which the lesion causes minimal expansion of the mantle © American Society for Clinical Pathology
AJCP / Case Report
❚Table 1❚ Findings in Inguinal Node, Porta Hepatis Node, and Bone Marrow Biopsy Specimens B-Cell Immunohistochemistry Biopsy Site
Timing
Morphology
Inguinal LN
Index specimen
Bone marrow
3 mo prior to index specimen
Effaced by vaguely nodular to diffuse infiltrate of monotonous small/ medium cells Aggregates of small mature lymphocytes
Porta hepatis 1 mo prior LN to index specimen
B-Cell Flow Cytometry
Dominant Population
Minor Population
Dominant Population
Minor Population
CCND1-IGH Cytogenetics FISH
>95% cells: CCND1–
Multifocal Mantle Cell Lymphoma In Situ in the Setting of a Composite Lymphoma Caroline Sloan,1 Qun-Bin Xiong, MD,1 Anne Crivaro, PhD,1 Sharon Steinman, MD,2 and Adam Bagg, MD1 From the 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, and 2St Luke’s Hospital at St Luke’s University Health Network, Allentown, PA. Key Words: Composite lymphoma; Mantle cell lymphoma in situ; Marginal zone lymphoma Am J Clin Pathol February 2015;143:274-282 DOI: 10.1309/AJCP06VIKFMTRCXD
ABSTRACT Objectives: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically defined but histologically inapparent neoplastic cells restricted to narrow mantle zones, without expansion or invasion beyond the mantle zone. We report a unique case of MCLIS associated with a much more manifest nodal marginal zone lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone marrow. Methods: Biopsies from all three locations were evaluated using standard H&E-stained sections, immunohistochemistry, flow cytometry, metaphase cytogenetics, and/or fluorescence in situ hybridization (FISH). Results: This case is unique for three reasons. First, the histologically covert mantle cell lymphoma was multifocal, detected in all three locations using one or more of flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS was always accompanied by a more histologically dominant MZL. Third, where evaluable, it did not grow in an appreciable mantle zone distribution, presumably due to destruction of the normal nodal architecture by the neoplastic MZL cells and the resulting absence of recognizable follicles and mantle zones. Conclusions: This unique case provides new insight into the pathogenesis of MCLIS.
274 Am J Clin Pathol 2015;143:274-282 DOI: 10.1309/AJCP06VIKFMTRCXD
Upon completion of this activity you will be able to: • describe the immunophenotype and hallmark translocation associated with mantle cell lymphoma. • define the features of mantle cell lymphoma in situ (MCLIS). • discuss the clinical implications of a diagnosis of MCLIS. • define potential early precursors of lymphoid neoplasms. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 307. Exam is located at www.ascp.org/ajcpcme.
In the past two decades, a number of case reports and case series have been published describing follicular lymphomas (FLs) and mantle cell lymphomas (MCLs) with “in situ” growth patterns.1 In 2008, the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues recognized these lesions as containing neoplastic cells that accumulate in the location normally occupied by their benign counterparts but are histologically and morphologically inapparent.1 In FL in situ (FLIS), also referred to as in situ FL-like B cells of uncertain significance, neoplastic cells accumulate within the germinal centers of secondary lymphoid follicles of otherwise reactive lymph nodes.2 In MCL in situ (MCLIS), also termed in situ MCL-like B cells of uncertain significance, neoplastic cells are almost exclusively restricted to the inner mantle zone or narrow mantles, without expansion of the mantle zone or invasion beyond the mantle zone.3 Occasionally, it may be difficult to distinguish between MCLIS and early involvement of overt MCL, in which the lesion causes minimal expansion of the mantle © American Society for Clinical Pathology
AJCP / Case Report
❚Table 1❚ Findings in Inguinal Node, Porta Hepatis Node, and Bone Marrow Biopsy Specimens B-Cell Immunohistochemistry Biopsy Site
Timing
Morphology
Inguinal LN
Index specimen
Bone marrow
3 mo prior to index specimen
Effaced by vaguely nodular to diffuse infiltrate of monotonous small/ medium cells Aggregates of small mature lymphocytes
Porta hepatis 1 mo prior LN to index specimen
B-Cell Flow Cytometry
Dominant Population
Minor Population
Dominant Population
Minor Population
CCND1-IGH Cytogenetics FISH
>95% cells: CCND1–
