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B M Osborne

Publications and source records attributed to B M Osborne.

At least 19 recordsLinked to original sources

Practicality of molecular studies to evaluate small lymphocytic proliferations in endoscopic gastric biopsies.

Fifteen endoscopic gastric biopsies (GBx) from 12 patients with small lymphocytic infiltrates morphologically raising a differential of indeterminate lymphocytic infiltrate versus mucosa-associated lymphoid tissue (MALT) lymphoma were analyzed genotypically after frozen-section identification of the abnormal lymphocytic infiltrate. Frozen-section immunoperoxidase immunophenotyping was equivocal in each case. All patients had abdominal pain attributable to superficial gastric ulceration, most often antral, without peripheral lymphadenopathy or hepatosplenomegaly. Rearrangement of the immunoglobulin heavy-chain gene (JH-R, seven patients) or kappa light-chain gene (JK-R, eight patients), was found in eight GBx from eight (seven stage IAE; one stage IBE) of 12 patients, establishing, in conjunction with the histologic features, a diagnosis of low-grade B-cell lymphoma. This diagnosis had not been tenable on multiple prior GBx, ranging from one to five per patient, over intervals of 1 month to 6.5 years (median 4.5 months). The T-cell receptor beta-chain gene retained germline configuration in all cases. Insufficient DNA for molecular studies was extracted from the GBx of two patients, one with JK-R (JH-G) on subsequent GBx and one without further GBx. One patient had two GBx, each demonstrating a single additional band in HindIII digests hybridized with the JH probe. No rearrangements were detected in either the BamHI or the EcoRI digests. Uninvolved tissue from this patient was not available for the exclusion of restriction fragment length polymorphism. Three GBx (two patients) showed germline JH genes (JH-G). One had a partial gastrectomy (histology: MALT lymphoma) in 1981 followed by GBx in 1983 (histologically benign) and in 1990 (JH-G), and negative esophagogastroduodenoscopy (EGD) in 1991 without biopsy. The other patient (two GBx with JH-G) had multiple subsequent abnormal EGD, but no biopsies since December 18, 1990. Adequate DNA for gene rearrangement studies can be extracted from GBx samples weighing as little as 20 mg. The two samples with insufficient DNA weighed 1 and 16 mg, respectively. Practically speaking, the remainder of a frozen block from a single GBx is adequate, thus allowing the screening of multiple endoscopic GBx by sequential frozen sections to determine which one contains the most extensive lymphocytic infiltrate for molecular study. Consistent results are obtained on samples weighing 40 to 60 mg. This method is a suitable alternative to kappa/lambda frozen-section immunoperoxidase immunostaining, which can be uninterpretable on endoscopic biopsies or small biopsies from other sites.

Adult

Progressive transformation of germinal centers: comparison of 23 pediatric patients to the adult population.

Approximately 10% of enlarged lymph nodes showing reactive follicular hyperplasia (RFH) will contain one or more progressively transformed germinal centers (PTGC). Comparison of 23 patients 16 yr old and younger (the pediatric group) of age to the adult population (greater than 16 yr old) indicates that most of the patients in each category present with a solitary asymptomatic enlarged lymph node (63% each group), usually cervical, and, while there may be recurrent lymphadenopathy showing RFH with PTGC (RFH/PTGC), evolution to Hodgkin's disease (HD) or other lymphomas is rare. Cases of PTGC unassociated with HD comprise the largest group: 70% (16/23 patients) of pediatric group; 60% (52/87 patients) of adult group. Five pediatric patients (22%) had antecedent HD (four males with lymphocytic predominance-nodular, NL&H HD; one female with nodular sclerosis, NSHD); this group is too small for comparison with adults. One patient (4%) subsequently developed NL&H HD; one patient had concurrent PTGC in the lymphoid rim surrounding NL&H HD. The 23 pediatric patients ranged from 4 to 16 yr (median 11, mean 11.3) with a male predominance (18 M, 5 F) similar to the adult population. Three differences occur comparing PTGC patients without associated HD from the two age groups. The less than or equal to 16 age group has a higher recurrence rate of PTGC (50 versus 23%); two or more biopsies showing PTGC after the initial biopsy was common, 19 versus 0%; and, morphologically, the pediatric cases unassociated with HD more often contain epithelioid histiocytic clusters (44 versus 0%), which may rim the PTGC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Adolescent

Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with enlarged lymph nodes.

In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Differentiation of T-cell lymphoma from Hodgkin's disease. Mitotic rate and S-phase analysis.

Flow cytometric DNA and proliferative compartment (S + G2M) analysis was performed on lymph nodes from 37 patients with Hodgkin's disease (HD) and on 16 lymph nodes plus 6 extranodal biopsies from 22 patients with peripheral T-cell lymphomas (PTCLs). The mitotic rate per 20 high-power fields (HPFs) was also determined for each case. The PTCLs showed significantly higher proliferative activity than the HD cases, as evidenced by a mean S + G2M of 12.0% versus 5.0% for HD and a median mitotic rate of 27 versus 5 mitoses per 20 HPFs in the HD cases. Because morphologic distinction, particularly of mixed cellularity HD (HDMC), from the diffuse small cleaved cell (DSCCL) or mixed cell (DMCL) pattern of PTCL may at times be difficult, these subgroups were compared separately. The 2 cases of DSCCL plus 12 of DMCL yielded a higher proportion of S-phase cells than the 9 HDMC cases with S + G2M means of 9.9% versus 3.3% and a higher mitotic rate, median 21 versus 7 per 20 HPFs. These findings suggest that S-phase determination and mitotic rate provide additional parameters in discriminating PTCL from HD in the most histologically similar cases.

Adolescent

Cat-scratch disease presenting as abdominal visceral granulomas.

Three cases of atypical, clinically unsuspected cat-scratch disease (CSD), diagnosed by demonstration of the CSD bacillus in an abdominal visceral organ, are presented. In two cases CSD bacilli were demonstrated for the first time in splenic granulomas in a child and in an adult with acquired immunodeficiency syndrome (AIDS)-related complex. In both cases, there was granulomatous hepatitis as well as splenitis. In the third case, the CSD bacillus was present in hepatic granulomas in an adult with granulomatous hepatitis. In all cases, granulomatous inflammation with suppuration in the viscera was identical to that previously described for lymph nodes in CSD. All patients eventually recovered completely. Clinical awareness of the broad spectrum of CSD should avoid the cost and morbidity of prolonged hospitalization, medications, and invasive surgery for a disease that is self-limited and not clearly responsive to antibiotics and that can usually be diagnosed by noninvasive means.

Adult

The value of immunophenotyping on paraffin sections in the identification of T-cell rich B-cell large-cell lymphomas: lineage confirmed by JH rearrangement.

Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

Adult

Contextual diagnosis of Hodgkin's disease and non-Hodgkin's lymphoma.

The pathologic evaluation of microscopic slides from patients with possible HD or NHL must be performed in the context of complete chronology of the patient's history. Advances in flow cytometry (S-phase analysis), immunophenotyping, and molecular genetics may be of value in diagnosis, classification, and prognostication. The Rye modification of the Lukes-Butler classification of HD has been stable since 1966 and is widely accepted because of its proven reliability. By contrast, the proliferation of classifications of NHL since 1966 speaks for imperfection, partially due to the still incomplete understanding of this diverse group of lymphoreticular malignancies. Successive classifications have incorporated immunologic relationships and concepts and added a clinically significant grading system. A goal of the working formulation was to allow translatability between classifications in the interest of comparison and communication of clinical and research results. Knowledge of the patterns of involvement and spread by HD and by the different categories of NHL helps to narrow the differential diagnosis of radiologic findings. An awareness of the benign, reactive processes and nonlymphoreticular malignant neoplasms that mimic HD and NHL is essential to avoiding misdiagnosis.

Diagnosis, Differential

Lymphoreticular disease masquerading as or associated with an inguinal or femoral hernia.

Twelve patients (eight men and four women) had previously undiagnosed lymphoreticular disease associated with or simulating an inguinal (nine) or femoral (three) hernia. The disease was present on the left side in eight. Four patients (three women and one man) did not have an actual hernia. Two of these women had a preoperative diagnosis of femoral hernia. Seven of the patients, including all of the women, had non-Hodgkin's lymphoma (three diffuse large cell, two follicular mixed cell and two follicular small cleaved cell) and one patient had lymphocytic predominance (nodular lymphocytic and histiocytic) Hodgkin's disease. No stage predominated. Inguinal lymph nodes from two patients showed, histologically, Kaposi's sarcoma and type I human immunodeficiency virus (HIV) associated disease. Each patient was homosexual and HIV seropositive. Changes suggestive of viral cause were present in the lymph node of one patient. The enlarged lymph nodes of the 12th patient showed stellate suppurative granulomas containing cat-scratch bacilli demonstrated by Warthin-Starry stain. Because of the special processing needs for lymphoreticular diseases and potential for misdiagnosis, surgeons, clinicians and pathologists should be aware of the spectrum of lymphoreticular processes occurring in lymph nodes associated with or masquerading as a hernia, particularly in women.

Adult

Small cell tumor of cervix with neuroepithelial features: ultrastructural observations in two cases.

Two cases of small cell tumor of the uterine cervix are reported in which electron microscopic studies indicated that the tumor cells were of neural crest origin. Both tumors behaved aggressively, and metastatic involvement of pancreas was demonstrated in one patient, while the second patient developed liver metastasis. The need to distinguish these neoplasms from squamous cell carcinoma of the cervix is stressed. The tumors are compared with small cell neuroepithelial neoplasms previously reported as adult neuroblastomas.

Carcinoma, Squamous Cell

Proteinaceous lymphadenopathy with hypergammaglobulinemia.

Three cases of a morphologically distinctive "sclerosis" of lymph nodes are presented. Two patients experienced recurring lymph node enlargement with associated mild malaise over an extended period. The first patient had unilateral axillary lymph node enlargement, but was asymptomatic and died of chronic obstructive pulmonary disease 17 years later with no evidence of lymph node enlargement at autopsy. Each patient had at least transient hypergammaglobulinemia, one with elevated IgM and IgA, one with elevated IgM, and one (from 1958) not further analyzed. Lymph node biopsies revealed extensive deposition of eosinophilic material in all three patients. Identical changes in lymph nodes have been described in chronic diseases. The eosinophilic material may be related to amyloid, but differs from it histochemically and ultrastructurally. The relationship of this lesion to the few cases reported as amyloidosis presenting as lymph node enlargement is discussed. Malignant lymphoma with sclerosis is the most important consideration in the differential diagnosis.

Adult

The opossum as an animal model for studying radiation esophagitis.

Six opossums were evaluated as a possible animal model of radiation esophagitis. In a single exposure to the esophagus, four animals received 60Co radiation of various doses; two served as controls. Pre- and postirradiation evaluations using fiberoptic endoscopy, mucosal biopsy, barium esophagography, and manometry were performed. Esophagitis developed at one week in irradiated animals. Opossums receiving 17.5, 20, and 22.5 Gy (1,750; 2,000; and 2,250 rad) became anorexic one week postirradiation, and abnormal motility subsequently developed. The controls and the animal receiving 15 Gy (1,500 rad) remained normal. Histological changes in the irradiated opossum esophagus resembled those found in humans.

Animals

Risk of radiation-related subsequent malignant tumors in survivors of Ewing's sarcoma.

Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 years, 4 new bone tumors were observed, whereas 1.2 x 10(-3) were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors.

Adolescent

Lymphangiographic changes after radiation therapy.

Lymphangiographic appearance following radiotherapy is described in 21 patients with pre- and posttherapy lymphangiograms. Following radiotherapy to normal lymphatics, decrease in nodal size and lymph vessel caliber is noted uniformly after 12 months. Before 12 months the development of these changes is variable and may not be seen, especially during the first several months. Following irradiation of abnormal lymph nodes, dilatation of the lymph vessels distal to the abnormal nodes may occur. These lymphangiographic findings can be related to histologic changes seen in lymph nodes after radiation therapy.

Adolescent

Radiographic findings of immunoblastic lymphadenopathy and related immunoblastic proliferations.

Immunoblastic lymphadenopathy is a recently recognized disorder of unknown etiology accompanied by clinical manifestations similar to lymphoma. Radiographic examinations of nine patients revealed multisystemic involvement and findings similar to those of lymphomatous processes. The diagnosis of immunoblastic lymphadenopathy should be considered when lung involvement accompanies mediastinal adenopathy and when the anterior mediastinal nodes are spared. One of the patients developed allergic pneumonitis which is interesting in light of recognition of immunoblastic lymphadenopathy as a hyperimmune phenomenon.

Humans