Synchronous malignant B-cell lymphoma and gastric tubular adenocarcinoma associated with paraneoplastic cutaneous vasculitis: hypereosinophilic syndrome with mixed cryoglobulinemia is an important sign of paraneoplastic syndrome

Abstract

Gastric adenocarcinoma developing concomitantly with a lymphoma is rare. Furthermore, B-cell lymphoma, originating from lymph nodes, with eosinophilia is extremely rare. We report here a case with a synchronous diffuse large B-cell lymphoma (DLBCL) and an early adenocarcinoma of the stomach. In addition, this case seemed to be associated with paraneoplastic cutaneous vasculitis caused by hypereosinophilic syndrome (HES) with mixed cryoglobulinemia (MC). Many neoplastic diseases that affect internal organs display cutaneous manifestations, which may be the presenting signs and symptoms of the underlying malignancy. In particular, the association between cutaneous vasculitis and malignancy has been widely reviewed, and recently neoplasms have been suggested to produce antigens and the resultant immune complex formations, activating the serum complement, thus cause paraneoplastic vasculitis. In this case, severe eosinophilia and cryoglobulinemia with low complements were observed in a laboratory test. A biopsy specimen from a skin lesion revealed leukocytoclastic vasculitis with severe perivascular infiltration of eosinophils. The cutaneous vasuculitis was considered to be a manifestation of HES with MC, although there were no etiological factors of HES and MC. Therefore, the vasculitis seems to be a symptom of paraneoplastic syndrome in this case. Our finding suggests that the potential presence of malignancies should be kept in mind as a possible underlying disorder especially in the presence of HES with MC; this possibility is interesting also as regards at least part of the pathogenesis for paraneplastic syndrome.

Keywords: cryoglobulinemia; malignant lymphoma; paraneoplastic vasculitis; tubular adenocarcinoma..

Figure 1

Skin lesions. (A) The gross appearance of purpura on the lower legs; (B, C) the histological findings of the purpura, showing massive infiltration of neutrophils and lymphocytes with deposits of fibrin on the vessel wall. Marked eosinophil and red blood cell infiltration is observed in the perivascular region. The cutaneous lesion was diagnosed as leukocytoclastic vasculitis with severe perivascular eosinophil infiltration. (Hematoxylineosin stain; magnification: B, 100× and C, 400×.)

Figure 2

Biopsy specimens from lymph node (A-C) and stomach (D-E), showing anti-CD20 antibody immunohistochemical staining (A) and anti-BCL2 antibody immunohistochemical staining of the lymph node specimen (B), magnification: 40−; hematoxylineosin staining of the lymph node specimen (C), magnification: 12.5−; and (D) the macroscopic finding of a biopsy specimen from the gastric lesion (indicated by arrow), and (E) hematoxylineosin staining, magnification: 10×. The specimen from the lymph node was strongly positive for CD20 and BCL2. Hematoxylineosin and BCL-2 staining showed some follicular formations and diffuse proliferation of the cells concomitantly. The patient was diagnosed with DLBCL transformed from follicular B-cell lymphoma. The gastroscopy specimen revealed irregular atypical cell proliferation in the mucosa, and the patient was diagnosed with early gastric cancer (tubular adenocarcinoma).

Figure 3

A schematic figure illustrating the hypothesis for paraneoplastic vasculitis with hypereosinophilic syndrome and mixed cryoglobulinemia. IC: immune complexes, APC: antigen-presenting cells, T: T-lymphocytes, B: B-lymphocytes, Eo: eosinophilia, MC: mixed cryoglobulinemia, HES: hypereosinophilic syndrome.