Eosinophilic Globules in 3 Cases of Glomeruloid Hemangioma of the Head and Neck: A Characteristic Offering More Evidence for Thanatosomes With or Without POEMS

Abstract

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.

Anastomosing Hemangioma of the Genitourinary System

“…6,8 Of interest, in the context of the current report, Montgomery and Epstein 2 found hyaline globules of endothelial cells in 2 of their 6 cases. Such globules have been described in cutaneous and soft tissue vascular lesions such as glomeruloid or papillary hemangioma [16][17][18][19] and in Kaposi sarcoma, 20,21 angiosarcoma, 22 granulation tissue, 20 pyogenic granuloma, 20 and littoral cell angioma of the spleen, 23 but no globules of this sort were described in the more recent report of renal capillary hemangiomas by Brown et al 1 These globules are a common finding in anastomosing hemangioma, which may facilitate the diagnosis but cannot be used in the differential diagnosis of Kaposi sarcoma. We interpret these granules as thanatosomes (Greek "death bodies"), secondary lysosomes whose degradation has been arrested so that the lysosomes expand, overfilled by phagocytized proteinaceous material.…”

“…Our immunohistochemical panel did not identify the nature of the protein in the thanatosomes and failed to support the previously stated theories that globules may represent phagocytized immunoglobulins or RBCs. 18,21,24,25 In terms of differential diagnosis, Kaposi sarcoma and well-differentiated angiosarcoma also contain hyaline globules. [20][21][22] No predisposing factors associated with Kaposi sarcoma or angiosarcoma were seen in our cases.…”

A case report of a renal anastomosing hemangioma and a literature review: an unusual variant histologically mimicking angiosarcoma

“…Extramedullary hematopoiesis and intracytoplasmic hyaline globules have been reported in some cases, but not in all [2,3]. It is worth mentioning that intracytoplasmic hyaline globules may facilitate but not confirm a diagnosis of anastomosing hemangioma, nor can it be a mark for differentiating benign or malignant tumors, for it can be observed in many other vascular lesions, including benign and malignant tumors such as papillary hemangiomas [15], pyogenic graulomas [16], Kaposi sarcomas [17], angiosarcomsa [18], and others. It has been interpreted as thanatosomes (secondary lysosomes), which show a positive PAS-D stain in all cases [2,17,18].…”

Reactive angioendotheliomatosis of the intestine in Crohn’s disease: A second case report with 10-year follow up

“…In brief, spindle cell hemangioma shows solid spindle cell proliferation and cavernous vascular spaces with plump, sometimes vacuolated endothelial cells [1]. Glomeruloid hemangioma shows capillaries forming renal glomeruli-like tuft and PAS positive eosinophilic hyaline globules in the cytoplasm of endothelial cells [11]. Epithelioid hemangioma is characterized by lobular arrangement of vascular channels lined by epithelioid endothelium and prominent eosinophilic/ lymphocytic infiltrate [1].…”