Schizencephaly in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs. MATERIALS AND METHODS: A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities. RESULTS: Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs. CONCLUSIONS: To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.

Rhinosporidiosis: three domestic cases.

Three cases of rhinosporidiosis in Americans who had not traveled abroad are reported. We believe this is the largest cluster of indigenous cases reported in the United States. The three patients had lived in rural northeast Georgia all of their lives. One had a polypoid conjunctival lesion, and the two others had nasal polyps. In each case, the diagnosis was made by demonstrating morphologically distinctive fungal elements in histopathologic sections. Clinically, rhinosporidiosis had not been suspected.

The pathology of alkaptonuric ochronosis.

The gross and microscopic pathology of alkaptonuric ochronosis is presented from a study of pathologic specimens from six cases in our files and from a review of the literature. Emphasis is placed on the most clinically relevant organ systems involved by ochronosis: musculoskeletal, cardiovascular, genitourinary, eye, and skin. Recent electron microscopic discoveries from several affected organs, including the synovium, articular cartilage, cardiovascular system, eye, and skin, are included in this report. In addition, the molecular pathology of alkaptonuria is briefly discussed. The pathologic literature regarding alkaptonurin ochronosis is fragmented, as most cases of this rare entity are reported individually or as small series of cases. A comprehensive review of alkaptonuria has not appeared since the clinicopathologic review of the world literature by O'Brien et al in 1963. The purpose of this report is to present an updated and unified pathologic study of alkaptonuric ochronosis.

An ultrastructural and light microscopic study of the synovium in ochronotic arthropathy.

The synovium in two well-documented cases of alkaptonuric ochronosis was studied by transmission electron and light microscopy. A feature of alkaptonuria previously unreported in the English-language literature was the presence of phagocytosis of large collagen fibrils by synovial macrophages in both cases. The origin of these fibrils appeared to have been shards of ochronotic cartilage and areas of metaplastic cartilage. This finding suggests that active remodeling of the synovial tissues occurs in advanced ochronotic arthropathy. Numerous shards of ochronotic cartilage were embedded in the synovium. In addition, small aggregates of large collagen fibrils encrusted with apparent ochronotic pigment were occasionally noted in the interstitium. These aggregates of ochronotic collagen are best described as microshards, and they have not generally been recognized in the literature. What appeared by light microscopy to represent ochronotic pigment deposition in interstitial collagen actually represented embedded microshards of ochronotic cartilage in the interstitium. Slender and elongated microshards were most likely to be confused by light microscopy as ochronotic interstitial collagen.

Cardiovascular ochronosis.

A 64-year-old man with alkaptonuric ochronosis required aortic valve replacement for severe aortic stenosis and single-vessel aortocoronary artery bypass grafting for a subtotally occluded obtuse marginal branch of the circumflex coronary artery. Operative findings included ochronosis of a partly calcified aortic valve and the aortic intima. The aortic valve and a punch biopsy specimen of the ascending aorta were removed at surgery and were studied with transmission electron microscopy and light microscopy. The ultrastructural studies of the aortic valve revealed intracellular and extracellular deposits of ochronotic pigment. A portion of the extracellular ochronotic pigment represented degenerated cells. Large deposits of extracellular ochronotic pigment were associated with areas of valvular calcification. Electron microscopic study of the aorta disclosed ochronotic pigment in macrophages and smooth-muscle cells. Aggregates of extracellular ochronotic pigment in the intima and media appeared to be in locations of necrotic cells. Light microscopy also showed intracellular and extracellular deposits of ochronotic pigment. Our study suggests that extensive extracellular deposits of ochronotic pigment in the aortic valve may serve as a stimulus for dystrophic calcification. This may play a role in the development of aortic valve calcification and aortic stenosis associated with alkaptonuric ochronosis. To our knowledge, this is the first ultrastructural study of the aortic valve and aorta in alkaptonuric ochronosis.

Ochronotic arthropathy. A comparative scanning electron microscopic and light microscopic study of the synovium in ochronosis.

The synovium in two cases of ochronosis was studied by scanning electron microscopy and light microscopy. Several features not yet described were seen by scanning electron microscopic examination and correlated with the light microscopic findings. This is the first report in the English language literature comparing scanning electron microscopic findings with the light microscopic findings in ochronosis.

Diagnosis of thoracic splenosis by tru-cut needle biopsy.

We present a case of thoracic splenosis diagnosed by tru-cut needle biopsy, which yielded histologically normal splenic tissue. This is the first report of a diagnosis of thoracic splenosis by needle biopsy. The patient had a history characteristic of thoracic splenosis. Autotransplanted splenic tissue functions and may provide some defense against serious infections. A conservative approach to diagnosis offers the advantages of preserving splenic tissue and avoiding thoracotomy.

Closure of membranous ventricular septal defect of heart by septal leaflet of tricuspid valve.

A case of spontaneous closure of a membranous ventricular septal defect by adhesion of the septal leaflet of the tricuspid valve is reported. There was evidence to suggest that thrombi developed in a pouch formed by the adherent leaflet, giving rise to emboli producing remote and recent infarcts in the brain.