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Follicular lymphoma presenting follicular papules in the skin: A case report

ularly shaped blood vessels proliferating mainly in the dermis, with an infiltrate of lymphocytes and eosinophils in the dermal stroma (Fig. 1b). A high-power view revealed the aberrant vessels lined by plump, epithelioid endothelial cells (Fig. 1c). The deep subcutaneous nodule consisted of a well-circumscribed but non-encapsulated proliferation of dilated blood vessels of various sizes (Fig. 1b). These proliferating blood vessels consisted of intermingled thick-walled and thin-walled vessels (Fig. 1d). Elastica van Gieson staining showed internal elastic lamina in very few vessels, indicating that most of the blood vessels were veins (Fig. 1e). An obvious arteriovenous shunt was not identified. These clinical and histopathological findings led to the diagnosis of angiolymphoid hyperplasia with eosinophilia (ALHE) associated with underlying arteriovenous hemangioma (AVH). The endothelial cells in ALHE were immunoreactive to hypoxia-inducible factor (HIF)-1a, and rarely in AVH (Figs 1f,g). No recurrence was seen during a 3-year follow up. Angiolymphoid hyperplasia with eosinophilia, also known as epithelioid hemangioma, is an uncommon benign vascular lesion with distinct clinicopathological characteristics. Its etiology and pathogenesis are still uncertain. There is considerable controversy whether ALHE is a reactive lesion or a true neoplasm. Olsen and Helwig found arteriovenous malformation (AVM) in 42% of ALHE, and regard AVM as a possible cause of ALHE. Other authors also reported cases associated with arteritis, thrombus and AVM, mentioning the causal relationship of arterial lesions to ALHE. Sun et al. postulated that local hypoxia may play a role in the pathogenesis of ALHE. Our patient had underlying AVH in combination with ALHE. AVH is a rare, benign, acquired vascular lesion of unknown pathogenesis. To our knowledge, AVH, which is a type of hemangioma, not malformation, has never been described as a comorbidity of ALHE. We hypothesized that our patient had local hypoxia due to underlying AVH and the hypoxic condition led to endothelial cell proliferation, causing ALHE. In this case, diffuse cytoplasmic and moderate nuclear immunoreactivity of the endothelial cells for HIF-1a was observed in ALHE. HIF-1 is an oxygen-dependent transcription factor, which plays a crucial role in the angiogenesis of tumors. If hypoxia occurs, the HIF-1a subunit becomes stable and interacts with co-activators to modulate its transcriptional activity. Overexpression of HIF-1a can lead to the production of various hypoxia-inducible mRNA, including the mRNA encoding vascular endothelial growth factor, platelet-derived growth factor B, erythropoietin, galectin-3, WT-1 protein and transforming growth factor-a, which are confirmed stimulators of endothelial cell proliferation. Hypoxia may also promote endothelial cell proliferation though the renin–angiotensin–aldosterone system. Coexistence of ALHE with underlying deep type AVH and the immunohistochemical results in our case favor the hypothesis that ALHE is a reactive lesion triggered by hypoxia.