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Plasmacellular Lymphadenitis in Neurodermitis
Path. Res. Pract. 178, 88-90 (1983)
Institute of Pathology, University of MiinsterlWestf., F.R.G.
Plasmacellular Lymphadenitis in Neurodermitis K.-M. MULLER
We examined a left inguinal lymph node from a 20-year-old female patient whose clinical diagnosis was given as "multiple lymphomas supraclavicular, axillary, inguinal".
Morphologic Findings. The structure of the lymph node with a maximum diameter of 4 ern is disintegrated by edema. Small follicles are increased in its cortical zone, there is a distinct hyperplasia of T regions. The most striking finding is a massive increase of mature and immature plasma cells (Fig. A-D). In addition, interdigitating reticulum cells and eosinophils are increasing in the course of pulpal hyperplasia. Capillary endothelia of dilated and numerically increased postcapillary venulesare swollen (Fig. B). In several parts even the node's capsule is populated with Iymphoplasmacytoid cells. Diagnosis and Differential Diagnosis. Severe plasmacytic lymphadenitis or Iympho-plasmacytic immunocytoma? The following anamnestic data were supplied for better interpretation and classification of the findings: The patient, now aged 20, had suffered since infancy from severe neurodermitis, asthma bronchiale, and allergy against antibiotics. Nodal swellings had increased recently. Sonography and computed tomography mdicated splenomegaly and lymphomas at the liver hilus. Among laboratory parameters BSR of 801120 mm and a broad-based peak of gamma globulins (34.4 relative %) With a total protein of 8 g % were the most striking features. Electrophoresis showed the following proportions: Albumins 44.5%, alpha-Lglobulin 4.5%, alpha-2-globulin 9.9%, betaglobulins 7.6%, and gamma globulins 34.4%. No paraproteins are identified in Immune electrophoresis, but the IgG fraction is increased, the Cj-fraction decreased. Bone marrow cytologyfails to show any sign of malignant lymphoma. Epicritical evaluation. Morphological findings can only be interpreted together with the clinical data. Accordingly, hyperplasia of the T-cellregions coinciding with activation of the B-cell system in this node have to be interpreted as an uncommonly strong dermopathic plasmacytic lymphadenitis associated with neurodermitis and atopy syndrome. The most relevant parameter for excluding malignant lymphoma is the absence of paraprotein observed by immune electrophoresis.
Comment and Survey of theLiterature about Plasmacellular Lymphadenitis with Neurodermitis Reactive inflammatory changes of lymph nodes, and their distinction from malignant lymphoma, present par-
ticular difficulties to the pathologist who has to examine an inguinal node without additional clinical dataI. With regard to the topographical area drained by the inguinal node, unspecific inflammatory changes of the node suggest primarily urogenital infections by gonococci, spirochaetes, viruses and mycoplasma. Reactive lymphoid hyperplasia is characterized by an increase in number and size of lmyph follicles with prominent germinal centers containing numerous mitoses and macrophages. Like in the present case, sinuses are usually prominent, their endothelia swollen. The node's pulpa shows a rather colorful hyperplasia of lively proliferating plasma cells together with macrophages and eosinophilic leukocytes. Relatively typical additional findings such as granulomas, abscesses, and small focal reactions of epitheloid cells will permit inferences from histomorphology alone, on potential agents such as tubercle bacilli, spirochaetes, clamydia, and viruses'. More frequently, however, the morphologic findings will merely allow for a diagnosis of lymphadenitis with some pointers to possibly systemic lymphadenopathy, as e.g. in rheumatoid disease, or in dermopathic lymphadenopathy in chronic skin affections. In addition to follicular hyperplasia in cortex and pulp of the node, this type of lymphadenitis is characterized by an uncommonly high content of plasma cells in the deeper regions of the cortex and in the pulpal region of the node. Binucleated plasma cells and Russell bodies are not infrequent, and plasma cells are also found occasionally within the germinal centers'. Massive and diffuse proliferation of plasma cells in some parts signals systemic rheumatoid or dermopathic lymphadenopathy. In severe chronic dermopathic affections such as psoriasis or neurodermitis, findings clinically and morphologically similar to those of our case were observed in 4.8%; men were more frequently affected than womerr'. Nodal findings are interpreted as a reaction to the draining of different skin antigens. On the other hand, the cause of atopic neurodermitis is seen in a defect of the cell-mediated immune system, as the peripheral blood of neurodermitis patients shows a reduction of the T lymphocyte compartrnent".
Plasmacellular Lymphadenitis
III
Neurodermitis . 89
Fig. A. Plasmacellular lymphadenitis in neurodermitis. Small recognizable lymph follicles, structure lossened by edema (x 140). Fig. B. Postcapillary venule with swollen endothelial cells (x 350).
Fig. C. Colorful hyperplasia of pulp with marked strong proliferation of plasma cells (x 350). Fig. D. Same picture in higher magnification (X 560).
Differential Diagnosis Differential diagnostic separation of plasmacellular follicular dermopathic lymphadenopathy in neurodermitis has to consider lymphogranulomatosis, mycosis fungoides, angioimmunoblastic lymphadenopathy, follicular malignant lymphoma, and atypical lymphoid hyperplasia. Mycosis may be associated with the features of dermopathic lymphadenopathy, and so the exclusion of mycosis cells with the typical cerebriform nuclei is needed.
Differentiation from malignant follicular lymphoma or lymphoplasmacytoid immunocytoma of low malignancy, requires the absence of transformation criteria and the immunohistochemical exclusion of monoclonal antibody formation in proliferating plasma cells. AIL is characterized, besides the proliferation of plasma cells, by a proliferation of postcapillary venules and of B-immunoblasts and by deposits of PAS-positive substances.
90 . Letters to the Case In atypical lymphoid hyperplasia, isolated or regional lymph node hyperplasia is found together with nodular or diffuse infiltration by a combined population of cells with many mitoses in the germinal centers. The terminology is based on the presence of cellular atypia with strong nuclear abnormality and many mitoses. Plasma cells and their precursors are polyclonal like in plasmacellular lymphadenitis, as evidenced by their surface markers. The essential criteria for the final classification of a plasmacellular lymphadenitis (plasmacytic dermopathic lymphadenopathy) however, are found in the clinical picture with its informations about the severity, duration and progress of the disease, and the laboratory data about absence of paraproteins.
References Dorfman RF, Warnke R (1974) Lymphadenopathy simulating the malignant lymphomas. Human Path 5: 519-550 I
2 Hurwitt E (1942) Dermopathic lymphadenitis: focal granulomatous lymphadenitis associated with chronic generalized skin disorders. J Invest Derm 5: 197-204 3 Ioachim HL (1982) Lymph Node Biopsy. J. B. Lippincott Comp., Philadelphia - Toronto 4 Luckasen JR, Sabad A, Goltz RW, Kersey JH (1974) T- and B-lymphocytes in neurodermitis atopica. Arch Derm 110: 375-377 5 Nosanchuk JS, Schnitzer B (1969) Follicular hyperplasia in lymph nodes from patients with rheumatoid arthritis. Cancer24: 343-354
Received December 2, 1982 . Accepted January 20, 1983
Key words: Plasmacellular lymphadenitis - Neurodermitis - Dermopatbic lymphadenopathy - Lymphoid hyperplasia - Immunocytoma Prof. Dr. K.-M. Muller, Institut fur Pathologie der Berufsgenossenschaftlichen Krankenanstalten "Bergmannsheil", Universitatsklinik, Hunscheidtstr. 1, D-4630 Bochum, FRG
Letters to the Case E. H. BETZ, Liege
The differential diagnosis between dermatopathic lymphadenitis and lymphoma is rendered more difficult by the not unusual association of the two lesions. Indeed an erythrodermia and an exfoliative generalized dermatitis are classically described as complications of various types of lymphomas (most frequently chronic lymphatic leukemia, lymphocytic lymphoma and Hodgkin's disease). It is widely accepted that the skin reaction is secondary to the tumor and is related to changes induced in the immunological status by the development of the lymphoma. These immunological changes are still largely unknown and vary probably from case to case. This could account for the diversity of the histological pictures which may be found in the literature for dermatopathic lymphadenitis. These variations themselves contribute to make the differential diagnosis more difficult. Foci of lymphomatous tissue and reactive areas of lymphadenopathic lymphadenitis may coexist in the same node, and it is sometimes difficult to distinguish them
from each other. Therefore, the correct diagnosis may require to examine several successive node biopsies and to take in account other clinical and biological data, as stressed by the author of the case report. When the lymphadenitis is characterized by an infiltration of numerous plasma cells, the differential diagnosis with lymphoplasmocytic immunocytoma must be evoked and confirmed by other biological tests. Finally as remembered in the report, dermatopathic lyrnphopathy may be associated with mycosis fungoides or the related Sezary's syndrome. Here the diagnosis requires an examination of the skin lesion although the histological pictures of mycosis fungoides at the erythematous stage may be quite unspecific. On the contrary, when an other type of lymphoma is suspected, an examination of the skin lesion is usually of no help, the skin tumor infiltration occurring much later than the dermatitis lesions. Prof. E. H. Betz, Universite de Liege, Anatomie Pathologique, Rue des Bonnes Villes, 1, B-4020 Liege, Belgium
Institute of Pathology, University of MiinsterlWestf., F.R.G.
Plasmacellular Lymphadenitis in Neurodermitis K.-M. MULLER
We examined a left inguinal lymph node from a 20-year-old female patient whose clinical diagnosis was given as "multiple lymphomas supraclavicular, axillary, inguinal".
Morphologic Findings. The structure of the lymph node with a maximum diameter of 4 ern is disintegrated by edema. Small follicles are increased in its cortical zone, there is a distinct hyperplasia of T regions. The most striking finding is a massive increase of mature and immature plasma cells (Fig. A-D). In addition, interdigitating reticulum cells and eosinophils are increasing in the course of pulpal hyperplasia. Capillary endothelia of dilated and numerically increased postcapillary venulesare swollen (Fig. B). In several parts even the node's capsule is populated with Iymphoplasmacytoid cells. Diagnosis and Differential Diagnosis. Severe plasmacytic lymphadenitis or Iympho-plasmacytic immunocytoma? The following anamnestic data were supplied for better interpretation and classification of the findings: The patient, now aged 20, had suffered since infancy from severe neurodermitis, asthma bronchiale, and allergy against antibiotics. Nodal swellings had increased recently. Sonography and computed tomography mdicated splenomegaly and lymphomas at the liver hilus. Among laboratory parameters BSR of 801120 mm and a broad-based peak of gamma globulins (34.4 relative %) With a total protein of 8 g % were the most striking features. Electrophoresis showed the following proportions: Albumins 44.5%, alpha-Lglobulin 4.5%, alpha-2-globulin 9.9%, betaglobulins 7.6%, and gamma globulins 34.4%. No paraproteins are identified in Immune electrophoresis, but the IgG fraction is increased, the Cj-fraction decreased. Bone marrow cytologyfails to show any sign of malignant lymphoma. Epicritical evaluation. Morphological findings can only be interpreted together with the clinical data. Accordingly, hyperplasia of the T-cellregions coinciding with activation of the B-cell system in this node have to be interpreted as an uncommonly strong dermopathic plasmacytic lymphadenitis associated with neurodermitis and atopy syndrome. The most relevant parameter for excluding malignant lymphoma is the absence of paraprotein observed by immune electrophoresis.
Comment and Survey of theLiterature about Plasmacellular Lymphadenitis with Neurodermitis Reactive inflammatory changes of lymph nodes, and their distinction from malignant lymphoma, present par-
ticular difficulties to the pathologist who has to examine an inguinal node without additional clinical dataI. With regard to the topographical area drained by the inguinal node, unspecific inflammatory changes of the node suggest primarily urogenital infections by gonococci, spirochaetes, viruses and mycoplasma. Reactive lymphoid hyperplasia is characterized by an increase in number and size of lmyph follicles with prominent germinal centers containing numerous mitoses and macrophages. Like in the present case, sinuses are usually prominent, their endothelia swollen. The node's pulpa shows a rather colorful hyperplasia of lively proliferating plasma cells together with macrophages and eosinophilic leukocytes. Relatively typical additional findings such as granulomas, abscesses, and small focal reactions of epitheloid cells will permit inferences from histomorphology alone, on potential agents such as tubercle bacilli, spirochaetes, clamydia, and viruses'. More frequently, however, the morphologic findings will merely allow for a diagnosis of lymphadenitis with some pointers to possibly systemic lymphadenopathy, as e.g. in rheumatoid disease, or in dermopathic lymphadenopathy in chronic skin affections. In addition to follicular hyperplasia in cortex and pulp of the node, this type of lymphadenitis is characterized by an uncommonly high content of plasma cells in the deeper regions of the cortex and in the pulpal region of the node. Binucleated plasma cells and Russell bodies are not infrequent, and plasma cells are also found occasionally within the germinal centers'. Massive and diffuse proliferation of plasma cells in some parts signals systemic rheumatoid or dermopathic lymphadenopathy. In severe chronic dermopathic affections such as psoriasis or neurodermitis, findings clinically and morphologically similar to those of our case were observed in 4.8%; men were more frequently affected than womerr'. Nodal findings are interpreted as a reaction to the draining of different skin antigens. On the other hand, the cause of atopic neurodermitis is seen in a defect of the cell-mediated immune system, as the peripheral blood of neurodermitis patients shows a reduction of the T lymphocyte compartrnent".
Plasmacellular Lymphadenitis
III
Neurodermitis . 89
Fig. A. Plasmacellular lymphadenitis in neurodermitis. Small recognizable lymph follicles, structure lossened by edema (x 140). Fig. B. Postcapillary venule with swollen endothelial cells (x 350).
Fig. C. Colorful hyperplasia of pulp with marked strong proliferation of plasma cells (x 350). Fig. D. Same picture in higher magnification (X 560).
Differential Diagnosis Differential diagnostic separation of plasmacellular follicular dermopathic lymphadenopathy in neurodermitis has to consider lymphogranulomatosis, mycosis fungoides, angioimmunoblastic lymphadenopathy, follicular malignant lymphoma, and atypical lymphoid hyperplasia. Mycosis may be associated with the features of dermopathic lymphadenopathy, and so the exclusion of mycosis cells with the typical cerebriform nuclei is needed.
Differentiation from malignant follicular lymphoma or lymphoplasmacytoid immunocytoma of low malignancy, requires the absence of transformation criteria and the immunohistochemical exclusion of monoclonal antibody formation in proliferating plasma cells. AIL is characterized, besides the proliferation of plasma cells, by a proliferation of postcapillary venules and of B-immunoblasts and by deposits of PAS-positive substances.
90 . Letters to the Case In atypical lymphoid hyperplasia, isolated or regional lymph node hyperplasia is found together with nodular or diffuse infiltration by a combined population of cells with many mitoses in the germinal centers. The terminology is based on the presence of cellular atypia with strong nuclear abnormality and many mitoses. Plasma cells and their precursors are polyclonal like in plasmacellular lymphadenitis, as evidenced by their surface markers. The essential criteria for the final classification of a plasmacellular lymphadenitis (plasmacytic dermopathic lymphadenopathy) however, are found in the clinical picture with its informations about the severity, duration and progress of the disease, and the laboratory data about absence of paraproteins.
References Dorfman RF, Warnke R (1974) Lymphadenopathy simulating the malignant lymphomas. Human Path 5: 519-550 I
2 Hurwitt E (1942) Dermopathic lymphadenitis: focal granulomatous lymphadenitis associated with chronic generalized skin disorders. J Invest Derm 5: 197-204 3 Ioachim HL (1982) Lymph Node Biopsy. J. B. Lippincott Comp., Philadelphia - Toronto 4 Luckasen JR, Sabad A, Goltz RW, Kersey JH (1974) T- and B-lymphocytes in neurodermitis atopica. Arch Derm 110: 375-377 5 Nosanchuk JS, Schnitzer B (1969) Follicular hyperplasia in lymph nodes from patients with rheumatoid arthritis. Cancer24: 343-354
Received December 2, 1982 . Accepted January 20, 1983
Key words: Plasmacellular lymphadenitis - Neurodermitis - Dermopatbic lymphadenopathy - Lymphoid hyperplasia - Immunocytoma Prof. Dr. K.-M. Muller, Institut fur Pathologie der Berufsgenossenschaftlichen Krankenanstalten "Bergmannsheil", Universitatsklinik, Hunscheidtstr. 1, D-4630 Bochum, FRG
Letters to the Case E. H. BETZ, Liege
The differential diagnosis between dermatopathic lymphadenitis and lymphoma is rendered more difficult by the not unusual association of the two lesions. Indeed an erythrodermia and an exfoliative generalized dermatitis are classically described as complications of various types of lymphomas (most frequently chronic lymphatic leukemia, lymphocytic lymphoma and Hodgkin's disease). It is widely accepted that the skin reaction is secondary to the tumor and is related to changes induced in the immunological status by the development of the lymphoma. These immunological changes are still largely unknown and vary probably from case to case. This could account for the diversity of the histological pictures which may be found in the literature for dermatopathic lymphadenitis. These variations themselves contribute to make the differential diagnosis more difficult. Foci of lymphomatous tissue and reactive areas of lymphadenopathic lymphadenitis may coexist in the same node, and it is sometimes difficult to distinguish them
from each other. Therefore, the correct diagnosis may require to examine several successive node biopsies and to take in account other clinical and biological data, as stressed by the author of the case report. When the lymphadenitis is characterized by an infiltration of numerous plasma cells, the differential diagnosis with lymphoplasmocytic immunocytoma must be evoked and confirmed by other biological tests. Finally as remembered in the report, dermatopathic lyrnphopathy may be associated with mycosis fungoides or the related Sezary's syndrome. Here the diagnosis requires an examination of the skin lesion although the histological pictures of mycosis fungoides at the erythematous stage may be quite unspecific. On the contrary, when an other type of lymphoma is suspected, an examination of the skin lesion is usually of no help, the skin tumor infiltration occurring much later than the dermatitis lesions. Prof. E. H. Betz, Universite de Liege, Anatomie Pathologique, Rue des Bonnes Villes, 1, B-4020 Liege, Belgium