PMC5614916_01
(A) Hematoxylin and eosin stain of a surgically removed axillary lymph node consistent with idiopathic multicentric Castleman's disease (iMCD). Low magnification highlighting a prominent paracortex encircling atrophic secondary follicles (original magnification, x10). (B) Hematoxylin and eosin stain focusing on an atrophic germinal center which is partially lymphocyte depleted and which is penetrated by a prominent, hyalinized blood vessel lined by plump endothelial cells with enlarged nuclei, giving the appearance of a lollipop. Note the marked vascular proliferation in the interfollicular areas (original magnification, x40). (C) CD138 staining of sparsely scattered plasma cells in the interfollicular areas, less abundant compared to what is observed in the plasmacytic histopathological variant of iMCD (original magnification, x10). (D) CD21 stain displaying a prominent network of follicular dendritic cells (FDCs) in an abnormal follicle with a concentric arrangement of the small lymphocytes of the mantle zone along with FDC nuclei (original magnification, x40). (E) Hematoxylin and eosin stain of bone marrow showing megakaryocytic hyperplasia with a mixture of small hypolobated megakaryocytes and others having a multi-separated nucleus (original magnification, x40). (F) Reticulin stain on the bone marrow trephine biopsy highlighting mild myelofibrosis (original magnification, x40).
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F1
Interfollicular areas showed a marked vascular proliferation and contained a small number of CD138-positive plasma cells (Figures 1A-D). A bone marrow trephine biopsy revealed megakaryocytic hyperplasia and mild reticulin myelofibrosis without abnormal lymphocytic infiltration (Figures 1E,F).
(A) Hematoxylin and eosin stain. Colon biopsy showing irregular thickening of the subepithelial basement membrane, encircling some capillaries, indicating a collagenous colitis (original magnification, x20). (B) Hematoxylin and eosin stain. Glandular atrophy in the gastric body with foci of intestinal metaplasia and deep lymphoplasmacytic infiltrates, suggestive of an autoimune gastritis (original magnification, x20). (C) Hematoxylin and eosin stain. Reactive periglandular chronic inflammation in the prostate (original magnification, x10). (D) Hematoxylin and eosin stain. Rare lobular non-necrotizing epithelioid granulomas with peripheral lymphoid ring are found in addition to unspecific portal inflammation (original magnification, x40). (E) Hematoxylin and eosin staining of a liver biopsy showing mild sinusoidal distension in the liver biopsy (original magnification, x20). (F) Hematoxylin and eosin stain. Bronchial wall containing lymphoplasmocytic aggregates of variable densities with crush artifacts (original magnification, x10).
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Colon biopsies showed a collagenous colitis rich in eosinophils (Figure 2A). Gastric biopsies revealed chronic inflammation and glandular atrophia with intestinal metaplasia of the fundus suggestive of an atrophic gastritis (Figure 2B). Prostatic biopsies showed mild chronic inflammation without neoplasia (Figure 2C). Liver biopsy showed mild sinusoidal distension, unspecific portal and lobular inflammation, and rare epithelioid granulomas without necrosis (Figures 2D,E). Finally, the patient underwent a bronchial biopsy showing unspecific chronic inflammation without granuloma, which was not suspicious for sarcoidosis (Figure 2F).
(A) Time course of the serum CRP (mg/l) and IL-6 (pg/ml) levels, and the different immunosuppressive drugs (corticosteroids, tocilizumab, and rituximab) administered to the patient. High values of IL-6 early after tocilizumab were excluded. (B,C) PET-CT scans showing pulmonary and mediastinal lymphadenopathies before (B) and after treatment with rituximab (C).
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Thus, treatment was initiated with high dose methylprednisolone (1 g/day for 3 days) transitioned to prednisone 1 mg/kg for several weeks, one single infusion of tocilizumab (8 mg/kg), and 1 week later rituximab 375 mg/m2 (total 4 weekly doses) (Figure 3A). In the following 5 years, the patient relapsed twice, each time about 1 year after rituximab was discontinued (Figure 3A). Five years after the diagnosis was made (before the second relapse), the PET-CT showed reduction of the lymphadenopathies (Figures 3B,C).