Search PubMed⌕ Search

Biomedical subjects

H Lumerman

Publications and source records attributed to H Lumerman.

At least 19 recordsLinked to original sources

Immunohistochemical detection of GLUT1, p63 and phosphorylated histone H1 in head and neck squamous intraepithelial neoplasia: evidence for aberrations in hypoxia-related, cell cycle- and stem-cell-regulatory pathways.

AIM: Most epithelial malignancies are characterized by multistep progression from preinvasive/intraepithelial neoplasia to invasive malignancy. Detection and grading of early squamous intraepithelial neoplasia may at times be problematic. The aim of this study was to examine the ability of immunomarkers GLUT1, phospho-histone H1 and p63 to detect such early lesions. METHODS: Sections of formalin-fixed paraffin-embedded tissue from 27 cases of squamous intraepithelial neoplasia, 26 associated with invasive carcinoma, were immunostained with anti-p63 (4A4; Santa Cruz), anti-GLUT1 (Chemicon) and anti-phospho-histone H1 (monoclonal 12D11) and compared with normal, hyperplastic and immature squamous metaplastic epithelium. RESULTS: Normal epithelium displayed phospho-histone H1 in scattered parabasal cells; p63 in the basal one-quarter to one-half of epithelium; and GLUT1 negativity or weak/equivocal mid-epithelial GLUT1+ foci. In hyperplasia phospho-histone H1+ cells were also limited to the parabasal layer; p63 positivity was essentially identical to that in normal epithelium; GLUT1 characteristically stained basal cells in rete-like areas. p63 staining in squamous intraepithelial neoplasia (grade 1) was indistinguishable from normal epithelial staining; in contrast, squamous intraepithelial neoplasia (grade 3) was readily apparent, with up to full-thickness p63 positivity. Squamous intraepithelial neoplasia (grade 1) was readily distinguishable from normal epithelium with both phospho-histone H1 and GLUT1 immunostaining; both markers were detected in cell layers above the parabasal layer. With both, progressively higher cell layers stained in proportion to the severity of the intraepithelial neoplasia, up to full thickness positivity in grade 3 squamous intraepithelial neoplasia. Squamous metaplasia and grade 3 squamous intraepithelial neoplasia were not distinguishable with p63 (both showed full-thickness staining) but were readily distinguishable with GLUT1 and phospho-histone H1 stains. GLUT1 appeared to be the most sensitive marker for all grades of intraepithelial neoplasia. CONCLUSION: Altered expression of all three markers was a common finding in squamous intraepithelial neoplasia, hence, dysregulation of cell cycle-promoting cyclin-dependent kinases (phospho-histone H1), altered stem cell regulatory pathways (p63) and enhancement of hypoxia-sensing pathways (GLUT1) are all early alterations in the progression of squamous malignancy of head and neck origin. A panel of all three may be a useful means of detecting squamous intraepithelial neoplasia.

Biomarkers, Tumor↗

Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

Adolescent↗

Epithelioid hemangioendothelioma of the maxilla: case report and review of literature.

Epithelioid Hemangioendothelioma (EH) is a rare, low-grade malignant vascular tumor, first defined as a soft tissue tumor by Enzinger and Weiss in 1982. The tumor was later reported in virtually all sites, including liver, lung, brain, and bone. The epithelioid neoplastic cells are of endothelial origin, staining positive for Factor VIII and CD-34. In our review of EH of bone medline literature, and including the present case report, a total of 73 cases were found. Forty-one (56%) patients had multifocal bone involvement and thirty-two (44%) patients had solitary EH of bone. Resection was the primary recommended treatment. Visceral involvement appears to affect prognosis and survival adversely. We report a case of EH of the maxilla, which occurred in a 32-year-old male.

Adult↗

Submandibular gland mucocele: diagnosis and management.

Mucoceles originating from the submandibular gland are extremely rare. A review of the English literature resulted in identification of only 5 such cases. We have diagnosed and treated 2 submandibular mucoceles. Both lesions were removed in continuity with the submandibular and sublingual glands. No complications and no recurrences have occurred to date. The diagnosis of these lesions is complicated because of the lack of specific clinical diagnostic criteria and the similarity between submandibular mucoceles and plunging or cervical ranulas. Computerized tomography and specifically the presence of a so-called "tail" sign is pathognomonic for plunging ranula. This sign is absent in mucoceles originating in the submandibular glands. The treatment strategies vary as well. A diagnostic algorithm and a surgical rationale for treatment of submandibular mucoceles are presented.

Adolescent↗

Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: identification and expression of a novel acid beta-glucosidase mutation.

The finding of extensive lytic lesions in the mandible of a 19-year-old Ashkenazi Jewish woman led to the diagnosis of Type 1 Gaucher disease. She had extensive skeletal involvement, marked hepatosplenomegaly, and deficient acid beta-glucosidase activity. Mutation analysis identified heteroallelism for acid beta-glucosidase mutations N370S and P401L, the latter being a novel missense mutation in exon 9. Expression of the P401L allele resulted in an enzyme with a reduced catalytic activity (specific activity based on cross-reacting immunological material approximately 0.21), which was similar to that of the mild N370S mutant enzyme. The expression studies predicted a mild phenotype for the proposita's N370S/P401L genotype which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mandibular lesions may be complicated by osteomyelitis, pathologic fracture, and tooth loss, regular dental assessments in Type 1 Gaucher patients should be performed.

Child↗

Graft-versus-host disease. Case report and discussion.

The graft-versus-host disease reaction is an immunologic consequence resulting from the grafting of immunocompetent cells from one individual to an immunocompromised host. The oral manifestations of this disease process include severe oral pain, xerostemia, ulcerative lesions, and mucositis. With appropriate history and diagnostic testing, these lesions can be differentiated from other oral diseases having similar clinical appearance.

Adult↗

Synchronous lingual granular cell tumor and squamous carcinoma. A case report and review of the literature.

Granular cell tumor (GCT) is a benign lesion with a preference for subcutaneous sites. Marked pseudoepitheliomatous hyperplasia, seen in 10% of GCTs, might be misdiagnosed as squamous cell carcinoma (SCC), and GCT in the oral tissues has been referred to as a medical curiosity in the literature. We report the clinicopathologic, immunohistochemical, and ultrastructural findings in a case of coexistent SCC and GCT in the tongue. There is no evidence in this case that suggests malignant transition of the GCT to carcinoma. To the best of our knowledge, this is the first report of synchronous GCT and SCC in the oral cavity.

Adult↗

Keratoameloblastoma of the maxilla. A case report and review of the literature.

The keratoameloblastoma is a rare histologic variant of the ameloblastoma. Review of the English language literature revealed five case reports of keratoameloblastoma. We report the sixth case of this tumor. The tumor developed in the right posterior maxilla of a 26-year-old African-American man and demonstrated aggressive clinical behavior, analogous to conventional ameloblastoma. The initial biopsy specimen showed extensive cyst formation, which histologically resembled odontogenic keratocyst. However, the lining epithelium varied in thickness and there was separation and edema between the basal cells and the rest of the epithelium. The basal cells were strongly adherent to the underlying stroma unlike the basal layer of the odontogenic keratocyst, where cleavage often occurs in this area. Additionally, although the basal cells were palisaded and demonstrated nuclear polarization in areas, they were cuboidal rather than columnar. The excision specimen revealed more of a solid ameloblastic component in addition to the cystic component seen on the initial biopsy. Nevertheless, it is possible that the ameloblastoma had developed in an odontogenic keratocyst. Alternatively, it can be postulated that the keratoameloblastoma consists of both cystic and solid components, the former being analogous to the cysts of the conventional ameloblastoma.

Adult↗

Glandular odontogenic cyst: report of a case and review of the literature.

The glandular odontogenic cyst is a rare jawbone cyst of odontogenic origin, first described in 1988 by Gardner et al. We describe a previously unreported case of a combined cyst composed of glandular odontogenic cyst and ghost cell keratinization that was present for 33 years. We also reviewed the published 38 cases of glandular odontogenic cyst found in the world literature and add this additional case.

Age Distribution↗

Oral epithelial dysplasia and the development of invasive squamous cell carcinoma.

Oral epithelial dysplasia, the histopathologic marker of a premalignant disorder of the mouth mucosa, may present clinically as leukoplakia, erythroplakia, or leukoerythroplakia. Its presence in lesions of the oral mucosa is predictive by a variable rate (6.6% to 36%) of transformation to invasive squamous cell carcinoma. We studied the clinical features and microscopic slides of 308 case of oral epithelial dysplasia in our biopsy service and retrospectively evaluated 44 of these with follow-up data for transformation to invasive squamous cell carcinoma. Forty-four patients had follow-up of more than 6 months with a mean follow-up time of 18.4 months. Twenty (45%) were clinically free of disease and 15 (34%) had recurrence of the dysplasia. An additional two cases of lower grades of the disease recurred as carcinoma in situ. Invasive squamous cell carcinoma developed in seven (16%) in a mean transformation time of 33.6 months.

Adult↗

Benign fibrous histiocytoma of the maxilla.

Benign fibrous histiocytomas of bone are unusual neoplasms that often are confused with metaphyseal fibrous defects. Although the two lesions have overlapping microscopic characteristics, they differ in their clinicopathologic presentations. This report describes the clinicopathologic features of the first reported case of benign fibrous histiocytoma involving the maxilla and the fourth description of this tumor in the jawbones. In addition, the concept of fibrohistiocytic lesions of bone is discussed with consideration of their pathologic classification and their clinical, radiographic, and microscopic differential diagnosis.

Adolescent↗

Oral Kaposi's sarcoma: a clinicopathologic study of 23 homosexual and bisexual men from the New York metropolitan area.

A total of 3970 cases of Kaposi's sarcoma (KS) associated with the acquired immunodeficiency syndrome had been reported to the Centers for Disease Control by the end of 1986. The prevalence of oral KS in patients with KS of the skin varies, reaching a maximum of 44% in one published study. We present a retrospective clinicopathologic analysis of 23 previously unreported cases of oral KS in male homosexual and bisexual patients from the New York metropolitan area. Our data reveal that 21 of the patients had KS confined to the oral cavity and that, in 16 cases, the oral KS was the first presenting sign of the acquired immunodeficiency syndrome. Sixteen of the 23 patients had solitary oral lesions. Nineteen of the tumors showed prominent endothelium-lined capillaries resembling lymphatics, 16 exhibited a prominent spindle cell component, and 17 demonstrated areas of fibrosis. Of the 13 patients for whom there was adequate follow-up information, five were dead within 6 to 15 months. All five deaths were due to Pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗

Recurrent botryoid odontogenic cyst (lateral periodontal cyst).

The terms botryoid odontogenic cyst and lateral periodontal cyst have both been used to describe a histologically distinct type of cyst characterized by a thin epithelial lining exhibiting focal thickenings or plaques. The cyst reported herein is a well-documented example of this type of cyst, which exhibited persistent and recurrent behavior.

Adult↗

Acute promyelocytic leukemia appearing as spontaneous oral hemorrhage: report of case.

Oral signs and symptoms may often signify a serious underlying systemic disease. This case report describes a 45-year-old Oriental male with spontaneous oral hemorrhage and submucosal bullae of 4 days' duration. These oral findings represent the initial manifestations of acute promyelocytic leukemia. An aggressive postdiagnostic course was taken; however, the patient died 8 days after the diagnosis was established.

Diagnosis, Differential↗

Pigmentation of the jawbones and teeth secondary to minocycline hydrochloride therapy.

Oral pigmentation due to minocycline hydrochloride (Minocin) therapy is an unusual and infrequently reported side effect of the drug. This report describes a patient on long-term minocycline therapy who presented with gingival pigmentation. Upon surgical exploration, the gingiva was noted to be normal in color, but the underlying bone was deeply pigmented. Via fluorescent microscopy, minocycline deposition within the alveolar bone was demonstrated.

Adult↗