Glomeruloid hemangioma - a specific cutaneous marker of POEMS syndrome

In December 1998, a 49-year-old woman was referred by the Department of Neurology to the Dermatology Clinic for evaluation of multiple, bright red papules on her face and trunk of 6 months' duration. Two years prior to the appearance of the cutaneous eruption she was, seen for intermittent numbness and burning sensation of both hands of several months' duration and was found to have decreased sensory and motor nerve conduction velocities. Electromyography suggested axongenic demyelinating polyneuropathy. On admission for further studies in April 1996, she was noted to have generalized skin hyperpigmentation and mild splenomegaly. Laboratory studies at that time revealed anemia [hemoglobin, 9.6 g/dL (normal male, 13.5-17.5 g/dL; normal female, 12.0-16.0 g/dL)], hypothyroidism [thyroxine, 3.86 ng/dL (normal, 5.0-12.4 ng/dL); triiodothyronine, 35.4 ng/dL (normal, 62-168 ng/dL); thyroid-stimulating hormone, 12.3 mIU/L (normal, 0.4-4.5 mIU/L)], and lambda-type immunoglobulin A (IgA) paraprotein in the serum. A bone marrow biopsy showed marked plasma cell infiltration. POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome was diagnosed at that time and she was treated with prednisolone (15-30 mg/day) and melphalan (75 mg/day). In 1997, she developed pulsatile headache and blurred vision. Increased intracranial pressure and hydrocephalus were found. Increased intracranial pressure was relieved by placement of a lumbar peritoneal shunt. In January 1998, she suffered from recurrent pleural effusion and ascites, which were treated by intermittent pleurocentesis and ascites tapping, respectively. Physical examination revealed generalized, diffuse, brown pigmentation of the skin. Multiple erythematous papules of 4-7 mm were noted on the face and trunk (Fig. 1). The skin on the hands, wrists, feet, and lower legs was taut, swollen, shiny, and sclerodermatous, Ascites and pitting edema of the lower legs, toes, and fingers were noted. A skin biopsy of a chest papule showed dilated dermal vascular spaces containing groups of vessels resembling renal glomeruli. The vessels were congested and hyaline globules were seen within the cytoplasm of the endothelial cells. Some endothelial cells were vacuolated (Fig. 2a,b). The eosinophilic hyaline globules were weakly positive to periodic acid-Schiff (PAS) stain after diastase digestion, but were negative for immunoglobulin staining (including IgA, IgG, IgM, and kappa, lambda light chain). The endothelial cells lining the capillary loops showed positive immunostaining for factor VIII-related antigen, CD34, and Ulex europaeus agglutinin (UEA)-1. These findings were consistent with glomeruloid hemangioma, as described by Chan et al. in 1990 (Chan JKC, Fletcher CDM, Hicklin GA, et al. Glomeruloid hemangioma. A distinctive cutaneous lesion of multicentric Castleman's disease associated with POEMS syndrome. Am J Surg Pathol 1990; 14: 1036-1046), except for negative immunoglobulin staining.