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The lymphoid follicle variant of dermatomyositis.

Radke J, Pehl D, Aronica E, Schonenberg-Meinema D, Schneider U, Heppner FL, de Visser M, Goebel HH, Stenzel W - Neurol Neuroimmunol Neuroinflamm (2014)

Bottom Line: Electron microscopy was used to confirm the light microscopic diagnosis of DM.Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy.The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neuropathology (J.R., D.P., F.L.H., H.H.G., W.S.) and Rheumatology and Clinical Immunology (U.S.), Charité Universitätsmedizin Berlin, Germany; and Departments of (Neuro) Pathology (E.A.), Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children's Hospital (D.S.-M.), and Neurology and Neurophysiology (M.d.V.), Academic Medical Centre, University of Amsterdam, the Netherlands.

ABSTRACT

Objective: To investigate the clinical and morphologic spectrum of early adult-onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin.

Methods: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed.

Results: Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy.

Conclusions: The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis.

No MeSH data available.


Related in: MedlinePlus

Histologic presentation and immunohistochemical patterns of muscle biopsiesSerial sections of muscle biopsy stained with hematoxylin & eosin revealed ectopic lymphoid follicle-like structures (patient 1: A and B; patient 2: C and D). Sections were stained with an antibody against CD45+ leukocytes (E) to highlight the follicle-like inflammatory infiltrate. CD68+ macrophages (F) were diffusely distributed throughout the perimysium. C5b-9 was mainly found in walls of small capillaries and on the sarcolemma of single muscle fibers (G, arrowhead). Electron microscopy revealed ultrastructural evidence of undulating tubules (patient 1: H, arrowheads, 50,000×; patient 2: not shown). Major histocompatibility complex (MHC) class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (I). Sarcolemmal MHC class I expression was detected on all muscle fibers (J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase staining revealed blue-stained fibers indicating reduced COX activity (K). The lymphoid follicle-like structures consisted of CD123+ dendritic cells (L), CD138+ plasma cells (M), and CD8+ (N) and CD4+ (O) T cells that were distributed around CD79a+ (P) B cells. Expression patterns of Bcl-2 (Q), Bcl-6 (R), and BOB.1 (S) illustrate lymphoid follicle-like structures with increased proliferative activity in the B-cell areas as indicated by Ki67/Mib-1 immunostaining (T). Scale bars: A, D, E, F, K: 200 µm; B, C, G, S: 50 µm; I, J, L–R, T: 100 µm.
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Figure 2: Histologic presentation and immunohistochemical patterns of muscle biopsiesSerial sections of muscle biopsy stained with hematoxylin & eosin revealed ectopic lymphoid follicle-like structures (patient 1: A and B; patient 2: C and D). Sections were stained with an antibody against CD45+ leukocytes (E) to highlight the follicle-like inflammatory infiltrate. CD68+ macrophages (F) were diffusely distributed throughout the perimysium. C5b-9 was mainly found in walls of small capillaries and on the sarcolemma of single muscle fibers (G, arrowhead). Electron microscopy revealed ultrastructural evidence of undulating tubules (patient 1: H, arrowheads, 50,000×; patient 2: not shown). Major histocompatibility complex (MHC) class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (I). Sarcolemmal MHC class I expression was detected on all muscle fibers (J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase staining revealed blue-stained fibers indicating reduced COX activity (K). The lymphoid follicle-like structures consisted of CD123+ dendritic cells (L), CD138+ plasma cells (M), and CD8+ (N) and CD4+ (O) T cells that were distributed around CD79a+ (P) B cells. Expression patterns of Bcl-2 (Q), Bcl-6 (R), and BOB.1 (S) illustrate lymphoid follicle-like structures with increased proliferative activity in the B-cell areas as indicated by Ki67/Mib-1 immunostaining (T). Scale bars: A, D, E, F, K: 200 µm; B, C, G, S: 50 µm; I, J, L–R, T: 100 µm.

Mentions: Muscle biopsies of both patients revealed extensive infiltration by inflammatory cells mainly in the perimysium and endomysium (figure 2, A–D). In addition, the infiltrates were located at perivascular sites. CD68+ macrophages (figure 2F) were diffusely distributed throughout the perimysium. MAC (C5b-9) deposition was mainly found on small capillaries and on the sarcolemma of single muscle fibers (figure 2G, arrowhead). MHC class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (figure 2I). Sarcolemmal MHC class I expression was detected on all muscle fibers with perifascicular enhancement (figure 2J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase histochemistry revealed scattered COX-negative fibers as a sign of accompanying mitochondrial dysfunction (figure 2K). CD123+ dendritic cells (figure 2L) and CD138+ plasma cells (figure 2M) were found in close proximity to T- and B-cell areas. The lymphoid follicle-like structures (LFLS) were mainly composed of CD45+ leukocytes (figure 2E) with CD8+ (figure 2N) and CD4+ (figure 2O) T cells distributed around CD79+ B cells (figure 2P). Expression patterns of peripheral Bcl-2 (figure 2Q), central Bcl-6 (figure 2R), and BOB.1 (figure 2S) paralleled the specific lymphoid follicle-like B-cell pattern. The Ki67/Mib-1 proliferation index was increased within the center of the follicle-like structures (figure 2T).


The lymphoid follicle variant of dermatomyositis.

Radke J, Pehl D, Aronica E, Schonenberg-Meinema D, Schneider U, Heppner FL, de Visser M, Goebel HH, Stenzel W - Neurol Neuroimmunol Neuroinflamm (2014)

Histologic presentation and immunohistochemical patterns of muscle biopsiesSerial sections of muscle biopsy stained with hematoxylin & eosin revealed ectopic lymphoid follicle-like structures (patient 1: A and B; patient 2: C and D). Sections were stained with an antibody against CD45+ leukocytes (E) to highlight the follicle-like inflammatory infiltrate. CD68+ macrophages (F) were diffusely distributed throughout the perimysium. C5b-9 was mainly found in walls of small capillaries and on the sarcolemma of single muscle fibers (G, arrowhead). Electron microscopy revealed ultrastructural evidence of undulating tubules (patient 1: H, arrowheads, 50,000×; patient 2: not shown). Major histocompatibility complex (MHC) class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (I). Sarcolemmal MHC class I expression was detected on all muscle fibers (J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase staining revealed blue-stained fibers indicating reduced COX activity (K). The lymphoid follicle-like structures consisted of CD123+ dendritic cells (L), CD138+ plasma cells (M), and CD8+ (N) and CD4+ (O) T cells that were distributed around CD79a+ (P) B cells. Expression patterns of Bcl-2 (Q), Bcl-6 (R), and BOB.1 (S) illustrate lymphoid follicle-like structures with increased proliferative activity in the B-cell areas as indicated by Ki67/Mib-1 immunostaining (T). Scale bars: A, D, E, F, K: 200 µm; B, C, G, S: 50 µm; I, J, L–R, T: 100 µm.
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Related In: Results  -  Collection

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Figure 2: Histologic presentation and immunohistochemical patterns of muscle biopsiesSerial sections of muscle biopsy stained with hematoxylin & eosin revealed ectopic lymphoid follicle-like structures (patient 1: A and B; patient 2: C and D). Sections were stained with an antibody against CD45+ leukocytes (E) to highlight the follicle-like inflammatory infiltrate. CD68+ macrophages (F) were diffusely distributed throughout the perimysium. C5b-9 was mainly found in walls of small capillaries and on the sarcolemma of single muscle fibers (G, arrowhead). Electron microscopy revealed ultrastructural evidence of undulating tubules (patient 1: H, arrowheads, 50,000×; patient 2: not shown). Major histocompatibility complex (MHC) class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (I). Sarcolemmal MHC class I expression was detected on all muscle fibers (J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase staining revealed blue-stained fibers indicating reduced COX activity (K). The lymphoid follicle-like structures consisted of CD123+ dendritic cells (L), CD138+ plasma cells (M), and CD8+ (N) and CD4+ (O) T cells that were distributed around CD79a+ (P) B cells. Expression patterns of Bcl-2 (Q), Bcl-6 (R), and BOB.1 (S) illustrate lymphoid follicle-like structures with increased proliferative activity in the B-cell areas as indicated by Ki67/Mib-1 immunostaining (T). Scale bars: A, D, E, F, K: 200 µm; B, C, G, S: 50 µm; I, J, L–R, T: 100 µm.
Mentions: Muscle biopsies of both patients revealed extensive infiltration by inflammatory cells mainly in the perimysium and endomysium (figure 2, A–D). In addition, the infiltrates were located at perivascular sites. CD68+ macrophages (figure 2F) were diffusely distributed throughout the perimysium. MAC (C5b-9) deposition was mainly found on small capillaries and on the sarcolemma of single muscle fibers (figure 2G, arrowhead). MHC class II was expressed by the lymphoid cells and was found on numerous muscle fibers, predominantly in the perifascicular area (figure 2I). Sarcolemmal MHC class I expression was detected on all muscle fibers with perifascicular enhancement (figure 2J). Combined cytochrome c oxidase (COX)/succinate dehydrogenase histochemistry revealed scattered COX-negative fibers as a sign of accompanying mitochondrial dysfunction (figure 2K). CD123+ dendritic cells (figure 2L) and CD138+ plasma cells (figure 2M) were found in close proximity to T- and B-cell areas. The lymphoid follicle-like structures (LFLS) were mainly composed of CD45+ leukocytes (figure 2E) with CD8+ (figure 2N) and CD4+ (figure 2O) T cells distributed around CD79+ B cells (figure 2P). Expression patterns of peripheral Bcl-2 (figure 2Q), central Bcl-6 (figure 2R), and BOB.1 (figure 2S) paralleled the specific lymphoid follicle-like B-cell pattern. The Ki67/Mib-1 proliferation index was increased within the center of the follicle-like structures (figure 2T).

Bottom Line: Electron microscopy was used to confirm the light microscopic diagnosis of DM.Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy.The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neuropathology (J.R., D.P., F.L.H., H.H.G., W.S.) and Rheumatology and Clinical Immunology (U.S.), Charité Universitätsmedizin Berlin, Germany; and Departments of (Neuro) Pathology (E.A.), Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children's Hospital (D.S.-M.), and Neurology and Neurophysiology (M.d.V.), Academic Medical Centre, University of Amsterdam, the Netherlands.

ABSTRACT

Objective: To investigate the clinical and morphologic spectrum of early adult-onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin.

Methods: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed.

Results: Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy.

Conclusions: The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis.

No MeSH data available.


Related in: MedlinePlus