Critical commentary.
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Carcinoma, Squamous Cell↗
Biomedical subjects
J G Strickler
Publications and source records attributed to J G Strickler.
Pretransplantation assessment of the risk of lymphoproliferative disorder.
Posttransplantation lymphoproliferative disorder (PTLD) is an uncommon but often fatal complication of solid organ transplantation that occurs in approximately 3% of patients. To determine the relative importance and relationship of potential risk factors for PTLD before transplantation (i.e., Epstein-Barr virus [EBV] serostatus of the recipient and the cytomegalovirus [CMV] sero-status of the recipient and the potential donor) and the principal risk factor after transplantation (immunosuppression with antilymphocyte antibody), we analyzed the findings for the first 381 consecutive adult nonrenal transplant recipients seen at Mayo Clinic. In the absence of the other risk factors, the incidence rate of PTLD for EBV-seronegative recipients was 24 times higher (95% confidence interval [CI]: 6.2, 89) than that for EBV-seropositive recipients. The additional risk factors of therapy with OKT3 for rejection and CMV seromismatch (i.e., a negative recipient and a positive donor) each further amplified this risk four- to sixfold. Together, all three risk factors acted synergistically to increase the incidence rate of fatal and/or CNS PTLD by a factor of 654 (CI: 368, 1,162) compared with the low incidence rate (.458 cases per 100 person years) when none of these risk factors were present. Pretransplantation determination of recipient EBV and CMV serostatus can identify a subgroup of patients whose risk for severe PTLD may preclude transplantation.
Adult↗
Management of stage IE primary gastric lymphoma.
From 1975 to 1991, stage IE gastric lymphoma was diagnosed or treated in 40 patients at our institution. Thirty-five evaluable patients were the subject of this analysis (median age, 63 years). All histologic specimens were reviewed and classified according to the working formulation. Immunohistochemical stains were performed in 33 of 35 cases. The following histologic subtypes were identified: 26 patients had diffuse large cell, 2 had diffuse mixed cell, and 7 had mucosa-associated lymphocytic lymphoma (small lymphocytic lymphoma with features of MALT lymphoma). Of the 35 patients, 30 (86%) underwent laparotomy, with subtotal or total gastrectomy performed in 29. After gastrectomy, 17 patients had radiation therapy, 3 had chemotherapy, 2 had radiation plus chemotherapy, and 7 had no further treatment. Five patients were diagnosed with endoscopic biopsy and had radiation therapy, chemotherapy, or both without further surgical treatment. The median follow-up period was 69.2 months. The commonest presenting symptom was pain. The 5-year disease-free survival was 90% for the entire group and 88% for the 28 patients with working formulation intermediate histology. For patients with MALT lymphoma, the 5-year disease-free survival was 100%. The prognosis for patients with stage IE working formulation intermediate-histology gastric lymphoma is good and for those with stage IE MALT lymphoma, excellent.
Adult↗
Somatic mitochondrial mutation in gastric cancer.
Likely hot spots for mutations are mitochondrial sequences as there is less repair and more damage by carcinogens compared with nuclear sequences. A somatic 50-bp mitochondrial D-loop deletion was detected in four gastric adenocarcinomas. The deletion included the CSB2 region and was flanked by 9-bp direct repeats. The deletion was more frequent in adenocarcinomas arising from the gastroesophageal junction (4/32, 12.5%) compared with more distal tumors (0/45). Topographical analysis revealed the absence of the deletion from normal tissues except in focal portions of smooth muscle in one case. In two cases, apparent mutant homoplasmy was present throughout two tumors, including their metastases. In the two other cases, the mutation was present in only minor focal portions ( < 5%) of their primary tumors. These findings document the presence of somatic mitochondrial alterations in gastric cancer, which may reflect the environmental and genetic influences operative during tumor progression.
Adenocarcinoma↗
Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection.
We studied open-lung biopsies from 17 patients with pulmonary lymphomatoid granulomatosis (LYG) using paraffin-section immunostains and Epstein-Barr virus (EBV) RNA in situ hybridization to assess the phenotype of these unique tumors and to clarify the role of EBV infection. Histologically, all cases demonstrated the characteristic mixed mononuclear cell infiltrate of lymphomatoid granulomatosis with variable numbers of cytologically atypical large lymphoid cells in a background of small lymphocytes. Paraffin-section immunostains in all cases showed a predominance of T lymphocytes. A minor population of CD20-positive large B lymphocytes was identified in 11 cases; immunoglobulin light-chain restriction was demonstrated in four of these and immunoglobulin gene rearrangements in another case. Nuclear labelling for EBV RNA was detected in 10 of these 11 cases and was confined to the population of large B lymphocytes. Staining for CD20 was absent in the remaining six cases, as was nuclear labeling for EBV RNA. However, the large atypical lymphoid cells stained for T-cell-lineage-specific antibodies in three of these cases. We conclude that some cases of lymphomatoid granulomatosis are B-cell lymphoma associated with EBV infection, whereas others are of T-cell origin and are probably unrelated to EBV infection.
Adult↗
p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail.
Genetic instability may underlie the etiology of multistep gastric carcinogenesis. The altered microsatellites observed in tumors with the ubiquitous somatic mutation (USM) phenotype may represent the expression of such instability. Similarly, p53 mutations may allow the accumulation of genetic alterations caused by multiple mechanisms. In 40 sporadic gastric adenocarcinomas, nine tumors (22.5%) with p53 mutations in exons 5-8, and six tumors (15%) with the USM+ phenotype, were detected. None of the tumors had both alterations. The tumors with p53 mutations were predominantly in the proximal stomach whereas the USM+ tumors were predominantly in the distal stomach. The mutant p53 alleles were homogeneously distributed throughout the primary tumors, but usually absent from adjacent normal or dysplastic epithelium, indicating that p53 mutations are typically acquired before the bulk of clonal expansion. The loss of mutant p53 alleles during progression was also rarely observed in metastatic foci. Altered microsatellites were homogeneously present in the USM+ primary and metastatic tumors and one synchronous tubular adenoma, but were not detected in adjacent normal and metaplastic epithelium. These findings also demonstrate that the USM+ phenotype is expressed before the bulk of clonal expansion. In most (5 of 6) USM+ tumors, the sizes of the altered microsatellites differed between regions, indicating that the instability usually persists during clonal expansion. These findings indicate that both p53 mutations and the USM+ phenotype are present prior to the bulk of tumor growth and therefore may contribute to, rather than be a late consequence of, malignant transformation.
Aged↗
Activation of c-erbB-2 and prognosis in ovarian carcinoma. Comparison with histologic type, grade, and stage.
BACKGROUND: Prior reports suggested that measuring c-erbB-2 activation in ovarian carcinomas might be valuable in predicting prognosis. The authors attempted to confirm these studies while specifically excluding tumors of low malignant potential. METHODS: The clinical and pathologic significance of c-erbB-2 oncogene activation was assessed in 56 ovarian carcinomas, none of which met histologic criteria for tumor of low malignant potential. RESULTS: By using an immunohistochemical technique previously validated in molecular studies, c-erbB-2 oncogene overexpression was identified in 10 of the 56 carcinomas but did not correlate with histologic type, histologic grade, International Federation of Gynecology and Obstetrics (FIGO) stage, or prognosis. Adverse prognostic factors included histologic type (serous carcinoma), high grade, and high stage (FIGO Stages III and IV). Grade and stage were highly correlated with each other and were more important prognostic indicators than histologic type. CONCLUSION: Measuring c-erbB-2 activation in ovarian carcinomas may not be of practical value in predicting prognosis when tumors of low malignant potential are excluded.
Adenocarcinoma, Clear Cell↗
Treatment of stage IE primary lymphoma of bone.
PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.
Adolescent↗
Polymorphic reticulosis: a reappraisal.
We studied 18 patients (15 men and three women) evaluated for a destructive sinonasal lesion that had been diagnosed as "polymorphic reticulosis." The histologic features of each lesion were those of angiocentric immunoproliferative lesions," characterized by atypical lymphoid infiltrates with polymorphous, angiocentric, and necrotic features; 13 were grade 2 and five were grade 3. The neoplastic cells in each patient had a T-cell phenotype. Epstein-Barr virus RNA was detected in the neoplastic cells of 17 of the 18 T-cell lesions. Initial treatment consisted of local radiation therapy in each patient, chemotherapy in two patients, and prednisone in another patient. Two patients were lost to follow-up and the other 16 had a median follow-up of 14 years, 2 months (range, 4 months to 32 years, 5 months). Four patients are alive and disease free, four patients died not of disease or complication of therapy, and eight patients died of disease. The Kaplan-Meier estimate of survival was 63% at 5 years and 50% at 15 years. Histologic progression of angiocentric immunoproliferative lesions from grade 2 to grade 3 was observed in two patients, and a correlation between angiocentric immunoproliferative grade and survival could not be detected. These data suggest that polymorphic reticulosis is an Epstein-Barr virus-related angiocentric T-cell lymphoma.
Adult↗
Herpes simplex infection causing acute necrotizing tonsillitis.
OBJECTIVE: To describe the clinical and pathologic features of acute herpetic tonsillitis and to compare the histologic findings with those of herpetic lymphadenitis. DESIGN: We present a case report of a 22-year-old woman with bilateral cervical adenopathy, acute tonsillitis, and suspected peritonsillar abscess. MATERIAL AND METHODS: Histologic examination of the excised tonsils demonstrated discrete necrotic areas that contained cells with intranuclear viral inclusions. RESULTS: The diagnosis of herpetic tonsillitis was confirmed by demonstrating herpes simplex virus (HSV)-infected cells on paraffin section immunostains and by positive HSV cultures of the tonsillar tissue. CONCLUSION: HSV infection is an uncommon cause of acute tonsillitis; the histologic findings are similar to those seen in herpes simplex lymphadenitis.
Acute Disease↗
Granuloma annulare in patients with malignant lymphoma: clinicopathologic study of thirteen new cases.
BACKGROUND: Reports of necrobiotic granulomas or granuloma annulare in patients with malignant lymphoma are rare. OBJECTIVE: Our intent was to determine any unique clinical or histopathologic features in patients with granuloma annulare and lymphoma. METHODS: We reviewed the medical records and biopsy material from 13 patients with granuloma annulare and lymphoma. RESULTS: Three patients had Hodgkin's disease and 10 had non-Hodgkin's lymphoma. The granuloma annulare lesions showed typical histopathologic features. However, the clinical pattern was frequently atypical, with painful lesions in unusual locations including the palms and soles. Three patients displayed granulomatous inflammation in noncutaneous sites, either within the malignant lymphoma or in uninvolved tissues, and all three had atypical clinical presentations of granuloma annulare. CONCLUSION: Granuloma annulare with atypical clinical presentations may be associated with an underlying hematopoietic malignancy and may be part of a generalized granulomatous reaction to malignant lymphoma.
Adult↗
Nasal T-cell lymphoma.
Nasal T-cell lymphomas represent a controversial subset of malignant lymphomas and include lesions previously termed midline malignant reticulosis, lymphomatoid granulomatosis, and polymorphic reticulosis. Nasal T-cell lymphomas are rare in Western populations and much more prevalent in Asian countries. Clinically, adult males are most often affected. Histologically, an angiocentric infiltrate composed of a spectrum of atypical cells is usually present. Phenotypically, the neoplastic cells lack expression of B-lineage markers, and usually express the T-lineage-associated markers CD2, CD45RO, and CD43; however, they often lack other pan-T-lineage markers. They often express the natural killer marker CD56, but usually lack the natural killer markers CD16 and CD57. Gene rearrangement studies have shown a germline configuration for the antigen receptor genes in the majority of cases. To date, evidence of Epstein-Barr virus has been consistently demonstrated, regardless of the geographic region studied. In situ hybridization studies have localized the Epstein-Barr virus to the atypical cells.
Female↗
Pancreatic lymphoma: is it a surgical disease?
Primary pancreatic lymphoma is a rare neoplasm that reportedly regresses promptly with aggressive chemotherapy. Recently, the role of surgical management has been relegated to biopsy alone. The aim of this study was to review our experience with primary pancreatic lymphoma and to determine the outcome of patients managed by radiation therapy and/or chemotherapy. From 1952 to 1991, 107 patients with non-Hodgkin's lymphoma involving the pancreas were identified. Twelve patients (11%) had primary pancreatic lymphoma. The presenting symptoms and signs were nonspecific: abdominal pain (83%), weight loss (50%), and a palpable mass (58%). Six of the 12 patients (50%) undergoing celiotomy had a preoperative diagnosis of pancreatic carcinoma. These lymphomas were large (x = 8 +/- 2 cm) and deemed unresectable because of size, alleged mesenteric vessel encroachment, regional lymph node metastasis, or because of an intraoperative diagnosis of lymphoma. Biopsy alone was performed in 50% of patients and biliary bypass and/or gastroenterostomy was performed in 25% of patients. A single resection (pancreatoduodenectomy) was performed 1 year after a full course of chemotherapy had failed. Ten patients, all of whom died of progressive lymphoma, received primary postoperative radiation therapy and/or chemotherapy, and no patient was disease-free at follow-up. Mean survival was 13 months for patients who received chemotherapy alone (n = 2), 22 months for those treated with radiation therapy only (n = 5), and 26 months for those receiving combined radiation therapy and chemotherapy (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Combined histochemical stains in the differential diagnosis of Cryptococcus neoformans.
Three combinations of histochemical stains were used to study 69 routinely processed tissues containing various "yeast-like" fungal organisms (Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Candida albicans). Fontana-Masson stain combined either with mucicarmine or Alcian blue produced distinctive staining of C. neoformans (Fontana-Masson-positive wall and mucin-positive capsule) that was not identified in other fungi. The Alcian blue stain combined with periodic acid-Schiff reaction also was useful for fungal classification, because the Alcian blue component reacted with only C. neoformans (capsule) and B. dermatitidis (wall) and the periodic acid-Schiff reaction reacted with the cell wall and body of each fungus. We concluded that the combined histochemical stains used in conjunction with morphologic study of hematoxylin and eosin- and Gomori methenamine silver-stained sections are helpful in the differential diagnosis of yeast-like fungal organisms.
Alcian Blue↗
Infectious mononucleosis in lymphoid tissue. Histopathology, in situ hybridization, and differential diagnosis.
The histopathologic features of tissue specimens from 16 patients with acute Epstein-Barr virus-induced infectious mononucleosis, which was confirmed by clinical and serologic methods, are described. The clinical course was usually self-limited (14 patients), but it resulted in the death of two patients, one of whom (patient with renal transplantation) was immunosuppressed. Each lymphoid tissue specimen, including those obtained from the lymph nodes (n = 9), tonsils (n = 5), spleen (n = 1), and appendix (n = 1), showed a nonuniform expansion of nonfollicular areas by a polymorphous population of lymphocytes, including transformed lymphocytes and immunoblasts. In situ hybridization demonstrated Epstein-Barr virus-infected lymphocytes in four of eight tissue specimens that were studied. Other histologic features included Reed-Sternberg-like cells, plasma cells, histiocytes, frequent mitoses, abundance of postcapillary venules, and necrosis. These histologic features should suggest a diagnosis of infectious mononucleosis rather than other processes, either benign or malignant, that can mimic it.
Adolescent↗
Detection of Epstein-Barr virus by in situ hybridization with a commercially available biotinylated oligonucleotide probe.
Epstein-Barr virus (EBV) nucleotide sequences can be detected in routinely processed tissues by in situ hybridization (ISH) with either radiolabeled or nonisotopic EBV probes. In this paper, we describe our nonisotopic ISH protocol for EBV detection with use of a triple-biotinylated oligonucleotide NotI/PstI EBV probe. We compared this technique with our radioisotopic ISH technique that uses a 35S-labeled EBV probe and found that the nonisotopic technique was as sensitive as the radioisotopic technique for detecting EBV-infected cells in tissues from patients with posttransplantation lymphoproliferative disorders. Furthermore, use of the biotinylated probe has several advantages over the 35S-labeled probe, including commercial availability of labeled probe, increased probe stability, decreased technical and development time, and ease of interpretation. We conclude that the nonisotopic ISH procedure is practical for use in diagnostic surgical pathology.
Biotin↗
Tryptophan-induced lung disease: an immunophenotypic, immunofluorescent, and electron microscopic study.
L-tryptophan (LT) has been implicated as a causal agent in the recently recognized eosinophilia-myalgia syndrome (EMS). Pulmonary complications occur in up to 60% of patients. Lung biopsies have shown chronic interstitial pneumonia, mild eosinophilia, vasculitis and perivasculitis, and hypertensive pulmonary arteriopathy. Open lung biopsies from two women who developed respiratory symptoms associated with LT EMS were studied with a panel of antibodies to lymphoid cells, by transmission electron microscopy and by direct immunofluorescence for immunoglobulin and complement. The majority of the cells infiltrating the interstitium and around vessels were T-cells, with a predominance of CD8+ cells. Numerous alveolar macrophages were also identified. Rare polyclonal B-cells were also present. Ultrastructural studies confirmed the presence of interstitial and perivascular lymphocytes as well as occasional eosinophils. The inflammatory cells were also present in vessel cells. Fibrointimal thickening was not observed in the sections studied ultrastructurally. Immunofluorescent staining for IgG, IgA, C3, C4, albumin, kappa, and lambda was negative. There was scattered staining for fibrinogen in alveolar spaces. The etiology of LT EMS is still under investigation, although a contaminant acting in conjunction with host factors is the favored hypothesis. The results of this study indicate that T cytotoxic/suppressor cells may be intimately involved in the pathogenesis of the lung injury.
Adult↗
Detection of c-erbB-2 activation in paraffin-embedded tissue by immunohistochemistry.
Commercially available monoclonal antibodies were tested for their ability to detect increased levels of c-erbB-2 protein in formalin-fixed, paraffin-embedded breast carcinomas. Of five antibodies studied, four (TAB-250, CB11, 3B5, and N3/D10) showed strong cytoplasmic membrane reactivity in 23% (11 of 47) of routinely processed tumors, although interpretation of the immunoreactivity with 3B5 and N3/D10 occasionally was difficult due to cytoplasmic granular staining. Since the c-erbB-2 oncogene is activated by DNA amplification and overexpression of mRNA and protein, the same tumors were analyzed for c-erbB-2 activation by other techniques. c-erbB-2 activation in these 11 tumors was confirmed by immunohistochemistry of frozen tissue (nine of nine tumors), in situ hybridization (nine of 11 tumors), and Southern blot analysis (five of eight tumors). In some of these tumors the failure to demonstrate c-erbB-2 DNA amplification may be due to the small percentage of malignant cells. One additional tumor showed probable c-erbB-2 protein overproduction based on strong immunoreactivity with two antibodies (TAB-250 and CB11), although no definite activation could be demonstrated by additional techniques. Three other tumors (6%) showed equivocal c-erbB-2 protein overproduction based on weak immunoreactivity only with TAB-250, although unequivocal activation could not be demonstrated by additional techniques. The 32 carcinomas (68%) that showed no significant immunoreactivity with any antibodies in routinely processed tissue also showed no detectable c-erbB-2 activation by additional techniques. We conclude that TAB-250 and CB11 are reliable antibodies for detecting c-erbB-2 protein overproduction in routinely processed tissue. TAB-250 also weakly stains a few tumors showing no definite c-erbB-2 activation by other techniques. Two additional antibodies (3B5 and N3/D10) detect c-erbB-2 protein overproduction in paraffin-embedded tissue, but are more difficult to interpret. A fifth antibody, TA-1, is an excellent reagent for use on frozen tissue, but prolonged formalin fixation may impair recognition of its antigenic epitope.
Adenocarcinoma↗