PMC4718299_01
(A) The spleen shows atypical histiocytes with nuclear polylobulation and anaplasia and erythrophagocytosis (H&E stain, 400x). (B) The bone marrow after 4 cycles of thalidomide/CHOP chemotherapy reveals many atypical multinucleated histiocytes (H&E stain, 400x). The atypical histiocytes (arrow) are immunohistochemically (C) negative for factor VIII and (D) positive for CD68. In contrast, megakaryocytes (arrowhead) are positive for factor VIII (C) and negative for CD68 (D).
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F1
B, respectively). By immunohistochemical staining, the atypical histiocytes were negative for CD1a, CD2, CD3, TIA-1, CD20, CD21, CD35, cytokeratin (AE1/AE3), HMB45, and factor VIII (Figure 1C), but positive for CD45, CD68 (Figure 1D), S-100 (focal), lysozyme (focal), CD52, CD30, and CD4 (weak).
The serial positron emission tomography-computed tomography scans (A) before and (B) after thalidomide/chemotherapy; (C) day +65 and (D) day +300 posttransplant show decreasing [18F]fluorodeoxyglucose (FDG) uptake within lymph nodes in the upper abdominal, paraaortic regions, and also in skull, clivus, left mandible, cervical, thoracic and lumbar spines, pelvic bones, sacrum, sternum, ribs, clavicles, right scapula, bilateral humeri, and bilateral femora. Arrows point at the newly increased FDG-avid lesions in the upper back, right lung, and several bones on day +300 (D) compared with those on day +65 (C) posttransplant.
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F2
A PET-CT scan on October 12, 2012 revealed extensive [18F] fluorodeoxyglucose (FDG)-avid lesions (Figure 2A). However, a follow-up PET-CT scan revealed decreased but still extensive skeletal and lymph node lesions (Figure 2B) on January 14, 2013. Follow-up PET-CT scans on days +65 and +300 revealed marked improvement of FDG-avid lesions compared to pretransplant findings (Figure 2C and D, respectively), although new lesions were noted on day +300.
H&E (400x, A, C, and E) and CD68 immunohistochemical (200x, B, D, and F) staining of serial bone marrow biopsies obtained before transplant, but after thalidomide/chemotherapy (A and B), day +301 (C and D), and day +366 after transplant (E and F). As highlighted by CD68 immunohistochemical staining, atypical histiocytes were markedly decreased on day +301 (note the active trilineage hematopoiesis by H&E stain) (D) compared with pretransplant findings (B). In contrast, extensive proliferation of atypical histiocytes with reduced hematopoietic activity was present on day +366 posttransplant (E, H&E stain, 400x; F, CD68, 200x).
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F3
Bone marrow studies on March 14, 2013 revealed recovery of normal hematopoietic elements, but presence of multinucleated cells and bizarre atypical histiocytes (Figure 3A), which stained positive for CD52, CD68 (Figure 3B), S-100, and lysozyme. A decrease of abnormal histiocytic proliferation was also documented in bone marrow aspirates on days +61 (data not shown) and +301 (Figure 3C and D). Fulminant recurrence of MNSGCT-associated histiocytic proliferation and HPS were documented with prominent bone marrow hemophagocytosis and extensive abnormal CD68+ histiocytic proliferation (Figure 3E and F).