Malignant proliferative angioendotheliomatosis or angiotropic lymphoma associated with a soft-tissue lymphoma.

We report a 63-year-old man with violaceous nummular patches on the trunk. Histopathologic studies were consistent with a diagnosis of malignant angioendotheliomatosis or angiotropic lymphoma. Immunohistochemical study of skin was positive for UCHL-1 antigen and leukocyte common antigen and negative for L-26, Ulex europaeus lectin I, vimentin, cytokeratin, and epithelial membrane antigen. Ultrastructural study ruled out an endothelial origin of the neoplastic cells. These data confirmed the diagnosis of malignant proliferative angioendotheliomatosis. Five years before, a soft tissue lymphoma had been excised. This is an unusual case of malignant angioendotheliomatosis for the following two reasons: (1) a previous association with a soft tissue lymphoma and (2) the rarely described T immunophenotype of neoplastic lymphoid cells.     

Reactive angioendotheliomatosis presenting as cellulitis

Reactive angioendotheliomatosis (RAE) is a diagnostically challenging condition characterized by multiple possible clinical presentations, which makes diagnosis challenging. We present a rare case of RAE mimicking cellulitis in a 74‐year‐old woman with a valvular disease and also end‐stage renal disease, for which she was being treated with haemodialysis.     

Intravascular and diffuse dermal reactive angioendotheliomatosis secondary to iatrogenic arteriovenous fistulas

Reactive angioendotheliomatosis is a rare benign process that has been mainly described in patients with systemic infections, such as subacute bacterial endocarditis or tuberculosis, and in association with intravascular deposition of cryoproteins. Histopathologically, it is characterized by a proliferation of endothelial cells within vascular lumina resulting in the obliteration of the involved vessels. Another rare variant of reactive angioendotheliomatosis has been described in the lower extremities of patients with severe peripheral vascular atherosclerotic disease. It consists of violaceous and purpuric plaques histopathologically characterized by diffuse proliferation of endothelial cells interstitially arranged between collagen bundles of the reticular dermis. This second variant has been named diffuse dermal reactive angioendotheliomatosis. We report two patients with reactive cutaneous angioendotheliomatosis appearing distally to arteriovenous fistulas used for hemodialysis because of chronic renal failure. The first patient showed intravascular reactive angioendotheliomatosis, while the second one had purpuric plaques that were characterized histopathologically by diffuse dermal angioendotheliomatosis. Both patients showed an arteriovenous "steal" syndrome with distal ischemia, and it is possible that a local increase of vascular endothelial growth factor, as is the case in hypoxia situations, induces the endothelial proliferation. To the best of our knowledge, cutaneous reactive angioendotheliomatosis has not been previously described in association with arteriovenous shunts.     

Malignant angioendotheliomatosis proliferans. Report of an autopsied case studied with immunoperoxidase

We report the autopsy findings in a case of malignant angioendotheliomatosis proliferans. Neoplastic cells stained positively for leukocyte common antigen, factor VII-related antigen, and IgG by the indirect peroxidase-antiperoxidase technique. The authors speculate that malignant angioendotheliomatosis proliferans represents a distinctive type of neoplasm that appears either to exhibit bidirectional lymphoid and endothelial differentiation or to consist of an heterogeneous population of cells.     

Angiotropic lymphoma: malignant angioendotheliomatosis.

Malignant angioendotheliomatosis is an angiotropic lymphoma that may present with clinical findings suggestive of thrombophlebitis or vasculitis. Examination of a biopsy specimen with special stains for leukocyte common antigen establishes the diagnosis. Although malignant angioendotheliomatosis is usually fatal, early treatment with chemotherapeutic agents is helpful. We review the characteristics and treatment of this uncommon disorder and present an illustrative case.     

Angioendotheliomatosis in a woman with rheumatoid arthritis

Reactive angioendotheliomatosis (RA) is a rare self-limited skin condition characterized histopathologically by a proliferation of endothelial cells within vascular lumina, usually as a result of different stimuli such as systemic infections, cryoproteinemias, monoclonal gammopathies, allergic conditions, severe peripheral vascular atherosclerotic disease, and iatrogenic arteriovenous fistulas. We report on a 67-year-old woman with a 20-year history of seropositive rheumatoid arthritis who presented with violaceous swelling of her left forearm. A skin biopsy revealed the histopathologic finding of RA with focal glomeruloid features and deposition of periodic acid-Schiff-positive material. In this systemic disorder, cutaneous manifestations may occur secondary to an immune complex-mediated vasculitic mechanism.     

Intralymphatic histiocytosis following placement of a metal implant

Intralymphatic histiocytosis (IH) is a rare condition first reported in 1994 by O’Grady et al. Less than 40 cases have been reported, with the majority occurring in patients with rheumatoid arthritis. We present a case of a 72‐year‐old man who developed an asymptomatic rash on his left upper arm 3 years after placement of a metal implant to stabilize a fractured humerus. Examinations revealed a poorly demarcated erythematous to brown indurated plaque with a pebbly surface overlying the inferior portion of the surgical scar. Biopsy revealed a mixed dermal infiltrate with a complex glomeruloid intravascular accumulation of histiocytes and neutrophils. Histiocytes were identified with immunostaining for CD68. Immunostains for CD31 and D2‐40 confirmed the intravascular location of the histiocytes. This reactive process is closely related to reactive angioendotheliomatosis, but is best classified as IH. This is the only case of IH reported in association with a metal implant of the upper arm and the fourth case reported in association with a metal implant. Although the pathogenesis of IH is unknown, a role for lymphatic stasis secondary to chronic inflammation or surgery has been suggested. This is a benign process with a chronic course, and there are no known efficacious treatments. Grekin S, Mesfin M, Kang S, Fullen DR. Intralymphatic histiocytosis following placement of a metal implant.     

Reactive angioendotheliomatosis: is it ‘intravascular histiocytosis’?

We report the case of a 68-year-old female with reactive angioendotheliomatosis (RAE). This case highlights the benign course of this condition and suggests that this entity might be an intravascular histiocytosis.     

Regression of cutaneous intravascular lymphoma with rituximab

Intravascular lymphoma, also known as malignant angioendotheliomatosis or angiotropic lymphoma, is a rare non-Hodgkin lymphoma that is usually fatal. It often presents with cutaneous and/or nervous system involvement, but the disease can involve any organ system. Clinical symptoms result from the occlusion of small vessels by tumor cells and fibrin. We present a case of cutaneous intravascular lymphoma successfully treated with rituximab, a recombinant antibody to CD20 antigen found on B lymphocytes.     

Angioendotheliomatosis associated with Castleman's lymphoma and POEMS syndrome

Castleman's lymphoma, a benign localized lymphoid hyperplasia, has been reported in association with POEMS syndrome, a multisystem reactive disorder that includes several skin manifestations. Benign reactive angioendotheliomatosis is a rare skin disorder that is associated with various systemic disorders. A patient with long-standing Castleman's lymphoma and POEMS syndrome also developed benign reactive angioendotheliomatosis.     

Reactive and malignant "angioendotheliomatosis": a discriminant clinicopathological study

In order to determine whether or not phenotypic differences existed between reactive angioendotheliomatosis (RAE) and malignant angioendotheliomatosis (MAE), we studied the histological and immunohistochemical features of 4 and 8 cases of these lesions, respectively. Antibodies to leukocyte common antigen (LCA), specialized B- and T-lymphocytic determinants, Factor VIII-related antigen (FVIIIRAG), blood group isoantigens A, B, and H (BGI), epithelial antigens, vimentin, and actin; and Ulex europaeus I lectin (UEL) were utilized. Cutaneous lesions in all cases of MAE were part of a disseminated, fatal, intravascular cellular proliferation, with highly atypical cytological features. Because one of the patients in this group had cardiac valvular vegetations at autopsy, this case had been reported previously as representative of RAE. However, the latter example, as well as all others of MAE, stained strongly for LCA, B-cell antigens, and vimentin in tumor cells. FVIIIRAG was seen focally in 6 cases, in cells entrapped in platelet-fibrin thrombi; however, UEL binding and reactivity for BGI were uniformly absent. Conversely, RAE was typified by a cytologically-bland intravascular proliferation, with actin-positive, perivascular, pericytic cuffs. All 4 patients in this group had cutaneous involvement only, and the lesions tended to be self-resolving. One had pulmonary tuberculosis, but evidence for an underlying infection was absent in the remainder of RAE cases. Immunohistologically, RAE displayed universal reactivity for FVIII-RAG, BGI, UEL, and vimentin, and negativity for LCA in intravascular cells. Neither MAE nor RAE showed the presence of epithelial determinants. These data indicate that MAE and RAE are clinicopathologically distinct entities, showing lymphoid and endothelial features, respectively. Because of the phenotypic properties of the former condition, it would appear advisable to substitute the term "intravascular lymphomatosis" for "malignant angioendotheliomatosis".     

Diffuse dermal angiomatosis: a variant of reactive cutaneous angioendotheliomatosis

Reactive angioendotheliomatosis (RA) is a rare, benign disease. Affected patients present with self-limited, erythematous to violaceous plaques. The clinical lesions are due to intravascular hyperplasia of cytologically banal endothelial cells in the dermis. We report 2 patients who presented with ulcerated, violaceous plaques on the lower extremities. Both had severe peripheral vascular atherosclerotic disease requiring bypass grafts. Unlike previously described cases of RA, our patient's lesions were due to a diffuse proliferation of endothelial cells in the reticular dermis with only minimal, focal intravascular proliferation of these cells. Positive immunostaining with antibodies to Factor VIII-related and CD34 antigens adds evidence that the proliferated cells in the dermis were endothelial cells.     

Reactive angioendotheliomatosis in the setting of antiphospholipid syndrome

A 31-year-old man with systemic lupus erythematosus and antiphospholipid syndrome developed erythematous purpuric plaques distributed over the lower chest, abdomen and upper thighs. Biopsy of lesional skin revealed intravascular proliferation of endothelial cells with associated microthrombi formation. The histological pattern was consistent with reactive angioendotheliomatosis, a rare reactive pattern seen associated with disparate medical conditions. The pathogenesis of the reactive angioendotheliomatosis in our patient was suspected to be related to his procoagulant state; thrombi formed despite a therapeutic international normalized ratio while on warfarin. His lesions began to resolve with the cessation of warfarin and commencement of subcutaneous enoxaparin, oral clopidogrel and oral aspirin. The skin biopsy findings were pivotal in influencing the change of therapy in this patient and decreasing his immunosuppression.     

Systemic proliferating angioendotheliomatosis

A 75-year-old female patient with neurological disturbances and numerous erythematous skin infiltrates is presented. Angioendotheliomatosis proliferans systematisata was diagnosed on histological detection of intravascular tumour cells in the cutaneous blood vessels. On immunohistochemistry and electron microscopy, the mononuclear tumour cells were identified as atypical B-lymphocytes. Our results provide further evidence that angioendotheliomatosis proliferans systematisata is a malignant angiotropic lymphoma with neurocutaneous manifestation.     

Pain reduction by dehydrated human amnion/chorion membrane allograft in nondiabetic leg ulcers might be an early indicator of good response: A case series

Dehydrated human amnion/chorion membrane allograft (dHACM) derived from placenta is increasingly used for skin and soft tissue repair in several medical specialties. Promising effects of dHACM were also reported in chronic venous and diabetic leg ulcers. However, dHACM is cost‐intensive and its effect on chronic leg ulcers of other etiologies and pain reduction is unknown. Clinical predictors of a favorable response to dHACM during the early treatment period could help to limit unnecessary costs. In our case series with six patients suffering from chronic lower leg ulcers of various etiology, the effect of dHACM once per week on reduction of pain and wound size during a 5‐week period was examined. dHACM resulted in effective pain reduction and improved wound healing in three patients with chronic leg ulcers due to calciphylaxis, chronic venous disease and reactive angioendotheliomatosis. Pain reduction after 1 to 2 applications of dHACM predicted a favorable healing response. Hence, our observation indicates that assessment of pain 3 weeks after initiation of dHACM may be a clinical predictor to justify dis‐/continuation of dHACM and thereby may help to limit costs.     

Angioendotheliomatosis proliferans systematisata

Angioendotheliomatosis proliferans systematisata comprises two different entities; a malignant and benign (reactive) form. The more common malignant form with a fatal prognosis should be termed intravascular or angiotropic lymphoma and is a multifocal systemic disease, which affects especially the small and middle-sized blood vessels of the skin and central nervous system. Reactive angioendotheliomatosis is a benign disease, often associated with an infectious disease (predominantly with subacute bacterial endocarditis). We report a 38-year-old woman with a reactive angioendotheliomatosis and a 68-year-old man diagnosed as having the rare T-cell type of intravascular lymphoma.     

Reactive angioendotheliomatosis in association with a well-differentiated angiosarcoma

A 55-year-old white female with a complex medical history including mixed connective tissue disease and peripheral vascular disease developed a group of red-purple papules on her proximal medial thigh that was followed, five months later, by the development of a large violaceous patch. She reported a history of radiation to this site (for melanoma) during her childhood. She was admitted to the hospital with a presumptive diagnosis of cellulitis, but failed to respond to antibiotics. A biopsy was performed and demonstrated a well-differentiated angiosarcoma arising in conjunction with reactive angioendotheliomatosis. Excision of the lesion was performed, and fifteen months of follow-up have shown no recurrence or metastasis.     

Localized reactive angioendotheliomatosis

We present a unique case of a woman with multiple painful dermal lesions localized to the left upper quadrant of the body. Histological investigation revealed microvascular thrombosis with capillary-wall proliferation. Further investigation revealed a very high anticardiolipin IgG titre and a left subclavian stenosis, presumably providing the reduced blood flow and relative hypoxia to allow microthromboses to occur in the presence of a thrombophilic tendency. Similar clinical and histological features have been reported in patients with the antiphospholipid syndrome and cases of reactive angioendotheliomatosis (RAE). This case represents a unique variant of RAE.     

Cutaneous reactive angiomatoses: patterns and classification of reactive vascular proliferation

New and relatively old types of vascular (capillary) proliferations in the skin have been described or better categorized in the last few years. They include reactive angioendotheliomatosis, acroangiodermatitis (pseudo-Kaposi sarcoma), diffuse dermal angiomatosis, intravascular histocytosis, glomeruloid angioendotheliomatosis, and angiopericytomatosis (angiomatosis with cryoproteins). Clinically, all of them present with multiple, erythematous-violaceous and purpuric patches and plaques, sometimes evolving toward necrosis and ulceration with a wide distribution but a propensity to involve limbs. Histologically, they are characterized by different patterns of intravascular or extravascular lobular or diffuse hyperplasia of endothelial cells, pericytes, and sometimes histiocytes. Although these angioproliferations can histologically mimic vascular tumors, they are reactive in that they seem to originate from the occlusion of vascular lumina by different localized or systemic disorders and the vascular proliferation stops after the inducing hypoxic stimulus has been withdrawn. In this article, the authors review all these forms of reactive angioproliferations in the skin, suggest a novel title, cutaneous reactive angiomatoses, and propose a unifying pathogenetic mechanism.     

Cutaneous collagenous vasculopathy associated with intravascular occlusive fibrin thrombi

Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that clinically resembles generalized essential telangiectasia with only 12 cases reported to date. The perivascular fibrosis is thought to be due to production of abnormal collagen by veil cells in the outer vessel walls as a result of unknown factors. This report is of an 84‐year‐old male with progressive telangiectasia. Biopsies showed characteristic features of CCV. In addition, there were multiple intravascular fibrin thrombi, some organizing and associated with endothelial cell hyperplasia with recanalization reminiscent of glomeruloid bodies and simulating reactive angioendotheliomatosis (RAE). Histochemically and ultrastructurally fibrin was noted within the vessel walls integrating into the fibrous tissue around the vessels; however, the patient had no evidence of coagulation disorder, cryoglobulinemia or cold agglutinemia. Immunofluorescence showed fibrinogen within the vessel walls but no immunoglobulins or C3. As well, there were minimal inflammatory cells. This suggests pauci‐inflammatory injury to the endothelial cells by unknown angiogenic factors causing local intravascular fibrin thrombi with fibrin leaking and incorporating into the vessel walls, eventually leading to reparative perivascular fibrosis. This case suggests that some cases of CCV are related to a primary local intravascular occlusive thrombotic microangiopathy. However, the primary triggering factor causing the endothelial cell damage has yet to be elucidated.