Glomeruloid hemangioma in normal individuals.

Glomeruloid hemangioma is a rare, histologically distinctive, cutaneous, benign vascular tumor, originally described by Chan et al. Glomeruloid hemangioma appears specific to polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), and is usually, but not always, related to Castleman's disease. We herein report two cases with glomeruloid hemangioma, without any features of the POEMS syndrome. Glomeruloid hemangioma requires a high index of suspicion for diagnosis. It could rarely present as a solitary finding, without any evidence of an underlying POEMS syndrome.

What was known?

Glomeruloid hemangioma is a specific marker for POEMS syndrome.

Few cases of glomeruloid hemangioma without POEMS syndrome have been reported in the literature.

Introduction

Chan et al.[1] has coined the term ‘glomeruloid hemangioma’ for a histologically distinctive, cutaneous, benign vascular tumor, which is considered to be a specific marker for the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS) syndrome. Clinically, it is characterized by a solitary or multiple blue-red papules and histologically it resembles renal glomeruli. The POEMS syndrome is a multisystem disease comprising of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy (M-protein), and skin changes. Contrary to what has been previously believed, glomeruloid hemangioma has recently been reported without any evidence of the POEMS syndrome.[2345] We support the observation with two similar cases.

Case Reports

Two young men, of age 18 and 22 years, presented with asymptomatic papulonodules of six months' and ten years' duration, respectively. One case had slowly progessing, multiple, pale, skin-colored papules and nodules present over the chin [Figure 1]. They were firm in consistency, varying in size from 1-2 cm. Few of the papular lesions were translucent in appearance and one of the papules had a ‘nipple-like’ projection. The lesions were non-compressible and non-tender. The second case had multiple, skin-colored, dome-shaped papules and nodules, present over the anterior and lateral aspect of neck, varying in size from 2 mm to 2 cm [Figure 2]. Systemic examination, including a neurological examination, did not reveal any abnormality.

Figure 1

Skin-colored papules and nodules on the chin, with a ‘nipple-like’ projection

Figure 2

Skin-colored, dome-shaped papules and nodules on the neck

Both underwent routine laboratory tests, which revealed no abnormality. No Bence–Jones proteinuria was detected in a sample from a 24-hour urine collection. Serum protein electrophoresis was normal. Abdominal ultrasound was normal and endocrinological evaluation, comprising of thyroid function tests, serum estradiol, serum testosterone, serum prolactin, and serum cortisol were all within normal range. A nerve-conduction velocity study and a total body skeletal survey were normal. Both cases had no abnormal findings on chest X-ray or computed tomography (CT) scans.

The histopathalogical examination revealed numerous dermal ectatic vascular spaces lined by flat endothelial cells. Inside these dilated vascular spaces, a conglomeration of capillaries lined by plump, swollen endothelial cells, filled with red blood cells, resembling renal glomeruli, were seen [Figures 3 and 4]. Variable-sized, homogeneous, eosinophilic, periodic acid-Schiff (PAS)-positive, diastase-resistant globules were present in the endothelial and stromal cells. The endothelial cells were positive for CD31 and CD34.

Figure 3

Photomicrograph showing glomeruloid aggregates of vascular structures in the dermis, resembling renal glomeruli (H and E, ×40)

Figure 4

Photomicrograph showing a glomeruloid structure with dilated capillaries lined by plump endothelial cells, filled with red blood cells (H and E, ×400)

Discussion

Glomeruloid hemangiomas represent vascular tumors, which present as small, firm, red-to-violaceous, dome-shaped papules, papulonodules, subcutaneous bluish compressible tumors, wine-red sessile or pedunculated papules, or lesions with cerebriform morphology. They range in size, measuring few millimeters to few centimeters in diameter, and are located mainly on the trunk and proximal limbs.[67] Rarely, glomeruloid hemangioma involving the face has also been reported.[89] Eruptive angiomatous lesions, similar to eruptive histiocytoma, have also been described.[10]

Histogenesis of glomeruloid hemangioma is still obscure. It probably represents a reactive endothelial proliferation, wherein, the overproduction of the vascular endothelial growth factor (VEGF), IL-6, IL-1β, tumour necrosis factor-α, and estrogens are believed to be responsible for angioma formation.[1] Hemangiomas in the POEMS syndrome fall into four histopathological categories: Microvenular hemangiomas, cherry hemangiomas,[11] multinucleated cell angiohistiocytomas,[12] and glomeruloid hemangiomas.[1] These histopathological features may be seen in different areas of the same biopsy specimen. They have been considered by some authors, to represent different stages in the development of the same lesion, which exhibit different degrees of endothelial proliferation, in response to angiogenic stimuli.[813] Tufted angioma is stated to be the most immature form of angiomatous lesions in the POEMS syndrome.[14]

A vascular lesion may appear well before the full blown POEMS syndrome develops, and therefore, a thorough evaluation and follow-up of patients with glomeruloid hemangioma, for potential development of this syndrome, is still recommended. The first case that was followed up for one year did not show any features of the POEMS syndrome and the other case was lost to follow-up.

What is new?

Glomeruloid hemangioma may have a varied clinical presentation, as seen in our cases.

Glomeruloid hemangioma presenting with a ‘nipple-like’ projection has not been reported to our knowledge.

Clinicians require a high index of suspicion to dignose glomeruloid hemangioma without the POEMS syndrome.