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Blue Rubber Bleb Nevus Syndrome is a rare, primarily sporadic condition characterized by vascular lesions principally involving the skin and gastrointestinal tract. Although considered a venous malformation, telangiectatic capillaries, arteriovenous malformations, and lymphangiomas have been reported, but a lymphangiomatosis-like growth pattern has not been described. This case of Blue Rubber Bleb Nevus Syndrome demonstrated a labyrinth of variably sized vascular spaces lined by an attenuated layer of bland endothelial cells, dissecting uterine tissues and sequestering remaining myometrium. Immunohistochemical profile of lesional endothelial cells from the myometrium included strong, diffuse CD31; variable CD34; strong, patchy D2-40; weak, patchy factor VIII-related antigen; focal linear subendothelial collagen type IV; Ki-67 in 1% of cells; and no GLUT-1 or WT1 expression. This report expands the morphological spectrum of vascular lesions in Blue Rubber Bleb Nevus Syndrome to include a lymphangiomatosis-like growth pattern and the immunohistochemistry suggests dual vascular and lymphatic differentiation, supporting the current belief that these lesions are malformations.

Angiomatous lesions of the lung are uncommon and not well characterized. We describe nine cases of a distinct lymphatic vascular lesion that we have termed "diffuse pulmonary lymphangiomatosis." Extrathoracic lymphangiomatous lesions were not identified. The patients comprised seven males and two females with a mean age at presentation of 10 years (age range, 1 month to 33 years). Six patients were younger than 10 years of age. Symptoms included "wheezing" or "asthma" (44%) and dyspnea (22%) present for 3 months to 20 years. Chest radiographs showed bilateral interstitial infiltrates, often greatest in the lower lobes. Pleural or pericardial effusions were present or developed in six patients. Pulmonary function tests showed in two patients and mixed obstruction and restriction in five patients. Open lung biopsies (nine patients) and autopsy (one patient) showed anastomosing endothelial lined spaces along pulmonary lymphatic routes (especially pleural and interlobular septal) accompanied by asymmetrically spaced bundles of spindle cells, which were prominent in six cases. Hemosiderin deposition often was present in the spindle cell areas and in the adjacent lung. The lining cells were positive for factor VIII-related antigen (eight cases) and Ulex europaeus I agglutinin (four cases). The spindle cells were reactive with antibodies to vimentin (nine cases), desmin (six cases), actin (seven cases), progesterone receptor (seven cases), and proliferating cell nuclear antigen (one case); they were negative for estrogen receptor (seven cases), keratin, (eight cases), and HMB-45 (eight cases). Diffuse pulmonary lymphangiomatosis was progressive in eight cases and was most aggressive in the youngest children. Two of the children have died, one of pulmonary hemorrhage and the other after heart-lung transplantation. Diffuse pulmonary lymphangiomatosis is distinct from lymphangiectasis, lymphangioleiomyomatosis, pulmonary capillary hemangiomatosis, Kaposi's sarcoma, and kaposiform hemangioendothelioma. Due to its distribution and histology, a lymphatic origin of the lesion is favored.