Biomedical subjects

John-Paul Bouffard

Publications and source records attributed to John-Paul Bouffard.

7 recordsLinked to original sources

PubMed2005

Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway.

Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR.

Adolescent↗

PubMed2004

Erdheim-Chester disease of the brain: cytological features and differential diagnosis of a challenging case.

Erdheim-Chester disease (ECD) is an uncommon, systemic xanthogranulomatous disorder, with distinct clinicopathological features, that is rarely expected preoperatively. We describe a case that presented in the brain of a 26-yr-old male patient and clinically mimicked the appearance of a neoplasm. The final diagnosis was a surprise. In retrospect, the diagnosis was suggested by the intraoperative "squash" preparations, which demonstrated a mixed cellular proliferation of lymphohistiocytic elements and large, multinucleated cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm. To the best of our knowledge, this is the first report detailing the cytopathological features of ECD.

Adult↗

PubMed2004

Basic pathology of the peripheral nerve.

Peripheral nerve pathology encompasses a complex array of disease processes that are poorly understood. This article provides a substrate for communication between pathologists and radiologists who are involved in the diagnosis and treatment of patients with peripheral neuropathy. The article is organized into sections on normal histology, routine morphologic techniques used in the study of peripheral nerve, and the basic disease patterns, followed by a brief discussion of selected neuropathies.

Axons↗

PubMed2004

Double immunolabeling of central nervous system atypical teratoid/rhabdoid tumors.

The central nervous system atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant tumor with a heterogeneous immunohistochemical profile and with some morphologic similarity to central nervous system primitive neuroectodermal tumors (PNET). Although several studies have investigated double immunolabeling in PNET, we are aware of no studies of double labeling of ATRT. A total of 10 ATRT from surgical and consultation materials at the Children's Hospital of Philadelphia were selected and stained for a variety of antigens using indirect immunofluorescence to detect single and double labeling. Most tumor cells showed only single labeling; rare cells showed double labeling as follows: 70% of tumors coexpressed (VIM) and glial fibrillary acidic protein (GFAP), 30% smooth muscle actin and GFAP, 20% epithelial membrane antigen (EMA) and VIM, 20% EMA/GFAP, and 20% EMA/SMA. These results are discussed in view of current debates over the histogenesis of CNS PNET and ATRT, and in reference to the classification of rhabdoid tumors as an entity or phenotype.

Actins↗

PubMed2003

Mesencephalic cryptococcal abscesses presenting with parkinsonism as an initial manifestation of AIDS.

Parkinsonism has been associated with HIV/AIDS and cerebral cryptococcal disease, but to date there has been no report of histological cryptococcal lesions in the substantia nigra (SN) in a patient with parkinsonism. We report on a case of a 63-year-old man who presented with tremor, gait disturbance, and mask-like facies, and showed cryptococcal meningoencephalitis with cryptococcal abscesses in the SN at autopsy, without Lewy bodies or significant degeneration of the SN neurons. Parkinsonism also represented the first manifestation of AIDS in this previously undiagnosed patient. This case highlights the importance of considering infectious etiologies in patients presenting with parkinsonism, and underscores the need for autopsy in evaluation of patients with new or unexplained movement disorders. Movement disorders in association with AIDS and mesencephalic mass lesions are discussed.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Primary ear and temporal bone meningiomas: a clinicopathologic study of 36 cases with a review of the literature.

"Primary" ear and temporal bone meningiomas are tumors that are frequently misdiagnosed and unrecognized, resulting in inappropriate clinical management. To date, a large clinicopathologic study of meningiomas in this anatomic site has not been reported. Thirty-six cases of ear and temporal bone meningiomas diagnosed between 1970 and 1996 were retrieved from our files. Histologic features were reviewed, immunohistochemical analysis was performed (n = 19), and patient follow-up was obtained (n = 35). The patients included 24 females and 12 males, aged 10-80 years (mean, 49.6 years), with female patients presenting at an older age (mean, 52.0 years) than male patients (mean, 44.8 years). Patients presented clinically with hearing changes (n = 20), otitis (n = 7), pain (n = 5), and/or dizziness/vertigo (n = 3). Symptoms were present for an average of 24.6 months. The tumors affected the middle ear (n = 25), external auditory canal (n = 4), or a combination of temporal bone and middle ear (n = 7). The tumors ranged in size from 0.5 to 4.5 cm in greatest dimension (mean, 1.2 cm). Radiographic studies demonstrated a central nervous system connection in 2 patients. Histologically, the tumors demonstrated features similar to those of intracranial meningiomas, including meningothelial (n = 33), psammomatous (n = 2), and atypical (n = 1). An associated cholesteatoma was identified in 9 cases. Immunohistochemical studies confirmed the diagnosis of meningioma with positive reactions for epithelial membrane antigen (79%) and vimentin (100%). The differential diagnosis includes paraganglioma, schwannoma, carcinoma, melanoma, and middle ear adenoma. Surgical excision was used in all patients. Ten patients developed a recurrence from 5 months to 2 years later. Five patients died with recurrent disease (mean, 3.5 years), and the remaining 30 patients were alive (n = 25, mean: 19.0 years) or had died (n = 5, mean: 9.5 years) of unrelated causes without evidence of disease. We conclude that extracranial ear and temporal bone meningiomas are rare tumors histologically similar to their intracranial counterparts. They behave as slow-growing neoplasms with a good overall prognosis (raw 5-y survival, 83%). Extent of surgical excision is probably the most important factor in determining outlook because recurrences develop in 28% of cases.

Adenoma↗

PubMed2002

Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 locus.

Cree leukoencephalopathy is a rapidly fatal infantile autosomal recessive leukodystrophy of unknown cause observed in the native North American Cree and Chippewayan indigenous population. We found in the brain of affected individuals the typical foamy cells with the oligodendroglial phenotype described in central hypomyelination syndrome/vanishing white matter, a syndrome related to mutations in the genes encoding the five subunits of the eucaryotic translation initiation factor eIF2B. In three patients of two Cree families, we found a homozygous missense mutation resulting in a histidine substitution at arginine 195 of epsilon-eIF2B.

Alleles↗