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M J Gaffey

Publications and source records attributed to M J Gaffey.

At least 19 recordsLinked to original sources
PubMed1992

Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.

Adrenal Cortex Neoplasms↗
PubMed1992

Lobular capillary hemangioma. An immunohistochemical study including steroid hormone receptor status.

Twenty-one lobular capillary hemangiomas (LCH), including lesions from six pregnant patients, were examined by immunohistochemical analysis. Antibodies to estrogen and progesterone receptor proteins were used to determine whether these steroid hormones play a direct role in LCH development and growth. All 21 LCHs were negative for both receptor proteins. Contrary to the association of LCH with pregnancy and oral contraceptive use, the absence of these steroid receptors strongly suggests that estrogen or progesterone are not directly involved in the formation of these lesions. All 21 LCHs were stained with Ulex europaeus lectin and with a panel of antibodies directed against cytokeratin, vimentin, Factor VIII, collagen Type IV, and muscle-specific actin. Endothelial cells in LCH, both in cellular proliferations with poorly formed lumens and in well-formed capillaries, were labeled by Factor VIII, Ulex europaeus lectin, and vimentin. A population of concentrically arranged, perivascular spindle-shaped cells was highlighted by positive staining for muscle-specific actin, collagen Type IV, and vimentin. The spindled cells were associated with both well-developed and immature vessels in all lesions. The appearance, immunophenotype, and location of these cells is consistent with a pericytic origin. Although the intimate association of both endothelial cells and pericytes suggests a reactive, as opposed to neoplastic, origin, other benign vascular tumors traditionally considered neoplastic have a similar bicellular composition. Accordingly, the findings neither support nor refute a neoplastic origin for LCH.

Adolescent↗
PubMed1992

Frequency of Epstein-Barr viral DNA in "Western" sinonasal and Waldeyer's ring non-Hodgkin's lymphomas.

Sinonasal non-Hodgkin's lymphomas (SNHL) of B- or T-cell immunophenotype have been associated with the Epstein-Barr virus (EBV) in Asian patients. We investigated eight sinonasal and 10 Waldeyer's ring NHL from Western patients for evidence of EBV genomes using a sensitive in situ hybridization technique. EBV DNA was detected in each of three sinonasal NHL with a T-cell immunophenotype and two of five cases with a B-cell immunophenotype. Two of 10 B-cell Waldeyer's ring NHL were positive for EBV genomes. In each positive case, EBV genomes were evenly distributed among the neoplastic cells, whereas no evidence of EBV in associated nonneoplastic lymphocytes or epithelium was seen. The results indicate that B-cell and T-cell sinonasal NHL are associated with EBV in Western as well as in Asian patients, and that EBV may have a role in oncogenesis in NHL of the upper aerodigestive tract. The strong association of EBV with nasopharyngeal carcinoma suggests that the anatomic site is important in the development of EBV-related neoplasms.

Adolescent↗
PubMed1992

Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas.

Ber-EP4 is a recently characterized monoclonal antibody directed against a cell surface glycoprotein that is putatively present on human epithelial cells but lacking on the mesothelium. To investigate the diagnostic efficacy of Ber-EP4 in distinguishing adenocarcinoma from mesothelioma, we studied formalin-fixed, paraffin-embedded sections from well-documented cases of adenocarcinoma (120 cases), adenomatoid tumor (nine cases), and malignant mesothelioma (49 cases). Of the 120 adenocarcinomas, 103 (86%) showed membranous Ber-EP4 positivity, with diffuse reactivity noted in 82 cases and focal staining in 21 cases. Reactivity with Ber-EP4 was also observed in two of nine adenomatoid tumors (22%) and 10 of 49 mesotheliomas (20%). Staining in the mesotheliomas was restricted to epithelioid areas and generally focal. In one mesothelioma, however, Ber-EP4 stained the majority of neoplastic cells. In contrast to previous reports, we conclude that positivity with Ber-EP4 does not exclude the diagnosis of mesothelioma. Nonetheless, most Ber-EP4-positive mesotheliomas exhibit only focal positivity, as opposed to the extensive staining commonly observed in adenocarcinomas. Ber-EP4 has diagnostic utility in the discrimination of mesothelioma from adenocarcinoma, but it is best utilized in an antibody panel that includes other markers of carcinomatous differentiation.

Adenocarcinoma↗
PubMed1991

Carcinomas with metaplasia and sarcomas of the breast.

The clinicopathologic, immunohistochemical, and flow cytometric characteristics of 34 cases of mammary carcinoma with metaplasia were compared with those of 20 cases of pure sarcoma of the breast. All 20 of the latter tumors showed the pattern of malignant fibrous histiocytoma. There were 20 cases of carcinoma with mesenchymal metaplasia, 7 cases of carcinoma with mixed epithelial (squamous) and mesenchymal metaplasia, and 7 cases of carcinoma with epithelial metaplasia (four mixed ductal/squamous and three pure squamous cell carcinomas). No patient with pure sarcoma had lymph node metastases develop; all nodal metastases were found in patients who had carcinoma with metaplasia, although in one case the carcinomatous component was seen only within a lymph node metastasis. Epithelial antigens were found not only within the epithelial elements of all cases of carcinoma, but also within the apparent mesenchymal elements of 44% of the carcinomas showing divergent differentiation. Flow cytometric analysis of eight cases of carcinoma with mesenchymal metaplasia showed aneuploidy/tetraploidy in six neoplasms. For patient management purposes, the distinction of pure sarcoma from carcinoma with metaplasia is important, but additional subclassification of carcinoma with metaplasia is of greater biologic than clinical interest.

Adult↗
PubMed1991

Herpes simplex lymphadenitis.

Localized herpetic lymphadenitis is an extremely uncommon complication of herpes simplex virus (HSV) infection. The authors report two cases of localized herpetic lymphadenitis, both showing well-circumscribed areas of necrosis containing cells with diagnostic intranuclear inclusions. Electron microscopic studies in both cases revealed characteristic viral particles, and in situ hybridization studies using a herpes simplex genomic probe demonstrated HSV DNA in both specimens. Immunohistochemical studies demonstrated that the cells containing the inclusions were stromal, not lymphoid, cells. Combining the current two cases with the six well-documented cases previously reported in the literature, seven of the eight cases of HSV lymphadenitis have developed in inguinal lymph nodes, with four occurring in patients with previously or subsequently diagnosed hematopoietic malignancies, including both patients in the current series.

Adult↗
PubMed1991

Anaplastic thyroid carcinoma with osteoclast-like giant cells. A clinicopathologic, immunohistochemical, and ultrastructural study.

Two anaplastic thyroid carcinomas with osteoclast-like giant cells (OCL-GC) are reported. Light microscopically, one case resembled an aneurysmal bone cyst with cellular connective-tissue septae separating cavernous, blood-filled sinuses. The second case had sheets of anaplastic cells and a separate focus of papillary carcinoma without areas of transition. Multinucleate OCL-GC, pleomorphic mononuclear cells, and histiocytoid mononuclear cells with nuclei similar to those within the OCL-GC were seen in each case. With formalin-fixed, paraffin-embedded tissue, the majority of OCL-GC and histiocytoid mononuclear cells in both cases showed immunoreactivity using monoclonal antibodies to vimentin and KP-1, with the latter preparation directed against cells of monocytic/histiocytic lineage. Staining for keratin, epithelial membrane antigen, neuron-specific enolase, chromogranin, calcitonin, and thyroglobulin was negative in all cell types. Ultrastructural examination of one case showed two distinct types of mononuclear cells--one with morphologic characteristics similar to those of the OCL-GC, and another with pleomorphic nuclei and short cytoplasmic extensions joined by poorly formed desmosomes. The findings indicate that the anaplastic thyroid carcinomas studied represent poorly differentiated epithelial tumors infiltrated by reactive OCL-GC of monocytic/histiocytic lineage apparently derived from histiocytoid mononuclear cells via cellular fusion.

Carcinoma↗
PubMed1991

Clear cell tumor of the lung. Immunohistochemical and ultrastructural evidence of melanogenesis.

Clear cell tumors of the lung (CCTL) are rare neoplasms of uncertain differentiation. A previous study of eight CCTL demonstrated a lack of epithelial features, but their exact nature remained unknown. In the current study of nine CCTL, immunohistochemistry using preliminary enzymatic digestion showed strong reactivity with the antimelanocytic markers HMB-45 (seven cases) and HMB-50 (six cases) and focal positivity for S-100 (nine cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu-7 (one case). Staining for cytokeratin, epithelial membrane antigen, chromogranin, and glial fibrillary acid protein was uniformly negative. Frozen-section immunoreactivity for vimentin and the antimelanocytic monoclonal preparation NKI/BETEB was noted in the one CCTL for which snap-frozen tissue was available. Ultrastructural examination of three glutaraldehyde-fixed CCTL showed rare neoplastic cells containing the full spectrum of melanosomes in two, one of which also contained neurosecretory-type granules. Aberrant melanosomal forms were identified in the third case. Melanosomes were not identified in the remaining five CCTL studied from formalin- or paraffin-retrieved material. The findings indicate that CCTL exhibits melanocytic differentiation. This feature may be of considerable value in distinguishing CCTL from other clear cell neoplasms.

Antibodies, Monoclonal↗
PubMed1991

Immunocytochemical characterization of a monoclonal antibody directed against mitochondria reactive in paraffin-embedded sections.

The monoclonal antibody mES 13 was previously produced against bacterially expressed BALB ras p21 and was reported to have both membrane and cytoplasmic reactivity in formalin-fixed, paraffin-embedded tissue sections. In the current study, the cytoplasmic reactivity of mES 13 is investigated and demonstrated to be mitochondrial. Immunoelectron microscopic studies showed specific labeling of mitochondria without labeling of other organelles. In normal tissues, the antibody strongly labeled tissues known to have large amounts of mitochondria such as renal tubules, hepatocytes, and myocardium. The pattern of reactivity of tumors generally mimicked that of normal tissues, with carcinomas and melanomas usually showing stronger staining than sarcomas and lymphomas. Two granular cell tumors were negative. Among renal neoplasms, mES 13 strongly labeled renal oncocytomas and granular cell renal cell carcinomas and showed weaker staining of clear cell and chromophobe cell tumors. The mES 13 antibody should be useful in the characterization and diagnosis of tumors in which oncocytoma is in the differential diagnosis, especially when only paraffin-embedded tissue is available for study.

Adenoma↗
PubMed1990

Spontaneous regression of hepatocellular carcinoma.

A surgically unresectable, biopsy-proven hepatocellular carcinoma (HCC) developed in a 63-year-old man with cirrhosis. He survived 24 months without treatment. During that time the tumor burden decreased as demonstrated both radiologically and by the normalization of alpha-fetoprotein levels. The patient died of complications secondary to repeated esophageal variceal hemorrhage. Necropsy demonstrated prominent, ulcerated esophageal varices and liver cirrhosis without evidence of neoplasia either grossly or on a subsequent thorough microscopic examination. This case represents the first confirmation of HCC spontaneous regression in which a primary histologic diagnosis was confirmed by immunohistochemical and flow cytometric DNA analysis, and where tumor regression was proven by a thorough necropsy examination.

Carcinoma, Hepatocellular↗
PubMed1990

Unusual variants of adrenal pseudocysts with intracystic fat, myelolipomatous metaplasia, and metastatic carcinoma.

Five previously unreported cases of adrenal pseudocysts are described that demonstrate a wider range of histologic appearances than has been previously recognized in these lesions. One pseudocyst removed from an asymptomatic 59-year-old female contained intracystic nests of cytologically malignant cells of unknown origin. Workup revealed a left breast mass, which on biopsy showed an infiltrating ductal carcinoma with neoplastic cells that were cytologically similar to those found within the cyst contents. Four other pseudocysts are described with variable numbers of intracystic vascular structures and benign adrenal cortical cells. In addition, intracystic mature adipose tissue was observed in all four cases, with myelolipomatous metaplasia found in one. Awareness of the wide histologic variability of these lesions should improve diagnostic accuracy and allow distinction from adrenocortical neoplasia and myelolipoma.

Adipose Tissue↗
PubMed1990

Clear cell tumor of the lung. A clinicopathologic, immunohistochemical, and ultrastructural study of eight cases.

We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eighth patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumor's histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered benign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially malignant neoplasms.

Adenocarcinoma↗
PubMed1990

Neuroendocrine carcinoma of the colon and rectum. A clinicopathologic, ultrastructural, and immunohistochemical study of 24 cases.

To further characterize the clinicopathologic spectrum of colorectal neuroendocrine neoplasia, 24 carcinomas with neuroendocrine differentiation were subtyped as either small cell neuroendocrine, oat cell variant (six cases), small cell neuroendocrine, intermediate variant (16 cases), or moderately differentiated neuroendocrine carcinoma (two cases). Five oat cell variants, 14 intermediate variants, and two moderately differentiated tumors were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen (EMA), neuron-specific enolase (NSE), chromogranin (CRG), synaptophysin (SYN), neurofilament, S-100 protein, carcinoembryonic antigen (CEA), and Leu-7. All tumors were immunoreactive for cytokeratin and the majority were also positive for EMA and NSE. Positivity for specific neuroendocrine markers was uncommon, with SYN reactivity noted in one oat cell variant and four intermediate variants, and CRG positivity observed in four intermediate variants and one moderately differentiated tumor. Ultrastructural analysis of four oat cell, eight intermediate, and one moderately differentiated tumor revealed neurosecretory-type, dense-core granules in all lesions, except two oat cell variants studied from paraffin-retrieved material. Hepatic and regional lymph node metastases were noted in five of six oat cell, eight of 16 intermediate, and two of two moderately differentiated tumors. Of 17 patients with follow-up (four oat cell, 11 intermediate, and two moderately differentiated tumors), only two individuals were alive after 1 year. There were no detectable differences in survival or response to treatment between morphologic subtypes. The prognosis of colorectal neuroendocrine carcinoma appears worse than for adenocarcinoma of comparable stage. Their distinction is thus warranted, especially in regard to the intermediate variant and moderately differentiated tumors, which may be potentially misinterpreted as forms of adenocarcinoma.

Adult↗
PubMed1989

The seroprevalence of cytomegalovirus among Virginia State prisoners.

A prevalence serosurvey of adult male prisoners entering the Virginia State Prison was conducted to evaluate the epidemiology of cytomegalovirus within this population. Four hundred and forty-five (97%) of 459 male inmates provided serum for analysis and 427 completed a detailed demographic questionnaire. Sera were tested for cytomegalovirus by passive latex agglutination and 64% were reactive. Multivariate discriminant analysis showed an independent association of seropositivity with age, non-white race, and a history of gonorrhea. There was no apparent contribution from admitted homosexual contact though this may have been under-reported. There was no correlation of seropositivity with intravenous drug use or with the length or number of prior incarcerations. Prisoners possess the same correlates for cytomegalovirus seropositivity as the general adult population; past imprisonment did not independently contribute to cytomegalovirus seropositivity.

Adult↗
PubMed1989

Vascular adrenal cysts. A clinicopathologic and immunohistochemical study of endothelial and hemorrhagic (pseudocystic) variants.

Three endothelial cysts and five hemorrhagic cysts (pseudocysts) arose in the adrenal glands of seven patients aged 23-73 years. Four patients were male and three were female. Five were symptomatic and gave abdominal pain as their chief complaint. Endothelial cysts were collapsed or filled with serous fluid, multiloculated, had an endothelial lining, and often contained adrenal cortex in their outer walls. The endothelial lining reacted only weakly for Factor VIII-related antigen (FVII-RAg), but it stained strongly for collagen type IV (C-IV). The lack of hemorrhage and the FVIII-RAg/C-IV staining pattern in endothelial cysts suggest lymphatic differentiation. Hemorrhagic cysts were spherical, firm masses containing clotted blood and hyalinized thrombus with attenuated adrenal cortex in the outer fibrous wall. Islands of intact cortical cells were present deep within the thrombi of four hemorrhagic cysts. Three of five hemorrhagic cysts stained strongly for FVIII-RAg and C-IV in irregular vascular channels of the attenuated cortex and within the cyst contents. These channels suggest that at least some hemorrhagic cysts arise when hemorrhage occurs in a preexisting blood vascular anomaly. Entrapment of cortical islands by extravasated blood in hemorrhagic cysts may be misdiagnosed as necrotic cortical neoplasm. To avoid confusion, one must recognize the normality of the entrapped cortical cells, identify an intrinsic vascular anomaly, and distinguish thrombus from necrotic tumor.

Adrenal Gland Diseases↗