Flow cytometry of lesional skin enhances the evaluation of cutaneous B‐cell lymphomas

Abstract

Background Cutaneous B‐cell lymphoproliferative lesions can pose diagnostic challenges. This study investigates the utlility of flow cytometry in 42 cases of suspected cutaneous B‐cell lymphoma. Methods All available cases were reviewed [World Health Organization‐European Organization for Research and Treatment of Cancer (WHO‐EORTC) classification]. Flow cytometry, immunohistochemistry and polymerase chain reaction‐immunoglobulin H (PCR‐IgH) analysis of blood and/or lesional skin were performed on primary cutaneous B‐cell lymphoma (pcBCL, 17 cases), secondary cutaneous BCL (scBCL, 8 cases) and atypical lymphoid hyperplasia (ALH, 17 cases). Results Flow cytometry of skin detected a B‐cell clone in 3/13 cases of ALH, 8/8 cases of pcBCL and 4/4 cases of scBCL, while PCR detected a clone in 3/14 cases of ALH, 4/15 cases of pcBCL and 6/8 cases of scBCL. Of eight cases of pcBCL analyzed by both methods, all eight were positive by flow while only three were positive by PCR. All cases positive by PCR were also positive by flow. Of five cases with both flow and light chain immunohistochemistry, all five showed light chain restriction by flow, while only two were positive by immunohistochemistry. Conclusion Flow cytometry is more sensitive than PCR in detecting B‐cell lymphoproliferative disorders (12/12 cases, 100% vs. 10/23 cases, 43%; p < 0.001). Furthermore, flow cytometry complements immunohistochemistry in the detection of light chain restriction.

Primary Cutaneous Follicle Center Lymphoma

“…Flow cytometry is more likely to detect both CD10 and BCL2 expression and can assess light chain restriction in B cells. 14,25 Some studies have found flow cytometry to be a more-sensitive measure of clonality than immunoglobulin gene rearrangement studies by polymerase chain reaction. 14,25 Two important drawbacks in the application of flow cytometry to skin biopsies include small sample size limiting specimen adequacy 12,14 and laboratory inexperience with skin specimens; it may be technically difficult to obtain sufficient cells in small skin biopsies that are rich in stroma.…”

“…13,18 Most cases do not spread beyond the skin (90%), although local recurrences are not uncommon (20%-30%). 2,4,[10][11][12][13]25 When it occurs, extracutaneous spread most commonly involves regional lymph nodes and the bone marrow. An important exception to the favorable prognosis in PCFCL is for PCFCL occurring on the legs.…”

Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates

“…Sixty-three relevant articles assessing kappa and lambda IHC or ISH in the evaluation of an atypical cutaneous or mucosal lymphoid infiltrate were identified ( Table 1, Table S1). 5,[9][10][11][12][13][14][15][16][17][18] 44 papers evaluated IHC exclusively, 10,11,13,15,17,[22][23][24][25][26][27][28][29]31,32,34,35,37,40,42,45,46,[48][49][50][52][53][54][55][57][58][59][60][61][62][63][64][65][66]…”

“…Figure 1A-F). 5,9,11,13,14,[16][17][18][22][23][24][28][29][30][31][32][33]35,38,39,41,43,44,49,50,[52][53][54]58,[60][61][62][63][64]66,68,69,72,73 16 papers exclusively examined primary cutaneous marginal zone lymphoma with kappa and lambda IHC/ISH, including lesions termed immunocytomas, amyloidomas, primary cutaneous plasmacytomas, and cutaneous follicular lymphoid hyperplasia with monotypic plasma cells. 13,14,18,24,29,30,32,43,44,[52][53]…”

“…13,14,18,24,29,30,32,43,44,[52][53][54]66,68,69,73 Other papers focused on extranodal marginal zone secondarily involving the skin or mucosa and other sites, 9 or a combination of primary and secondary MZLs. 11,23,24,28,31,50,[62][63][64] The MZLs studied included plasma-cell-rich variants, in which plasma cells made up 50% or more of neoplastic cells. 11,18,23,24,28,31,35,41,43,50,52,54,62,63 Other lymphomas examined using kappa and lambda IHC or ISH included the relatively skin-specific entities follicle center lymphoma (FCL) 5,16,23,28,37,41,56,61,[64]…”