Morphologic, immunphenotypic and clinical discriminators between T-cell / histiocyte-rich large B-cell lymphoma and lymphocyte-predominant Hodgkin lymphoma

Features of T-cell/histiocyte rich large B-cell lymphoma [THRLBCL] overlap with those of lymphocyte predominant Hodgkin lymphoma [LPHL]. The two lymphomas may represent a spectrum of the same disease, and differentiation between the two can sometimes be difficult. We looked at histomorphologic, immunophenotypic and clinical information that may help differentiate the two entities. Cases of THRLBCL and LPHL were blindly reviewed and studied for histological pattern [nodular vs. diffuse], nuclear features and pattern of expression of CD20, CD30, CD57, epithelial membrane antigen [EMA] and Epstein-Barr virus [EBV]. A score encompassing diffuse histology, high nuclear grade, CD20 single-cell pattern, CD30+, CD57-, EMA-, and EBV+ was estimated for the diagnosis of TCHRLBCL. There were 58 cases, including 30 cases of TCHRLBL and 28 cases of LPHL. The median age was 36 years for TCHRLBCL and 21 years for LPHL [P=0.0001]. Three types of nuclei were identified [lymphocytic/histocytic, Reed-Sternberg and centroblast-like]. The latter two high-grade nuclei were suggestive of TCHRLBCL. TCHRLBCL and LPHL, respectively, showed diffuse histology, 90% vs. 4% [P=0.001], single CD20+ cells, 93% vs. 3.5% [P=0.00004], CD30+ cells, 30% vs. 0% [P=0.01], CD57+ cells, 41% vs. 93% [P=0.008], EMA+ cells, 27% vs. 60% [P=0.113], EBV+ cells, 24% vs. 0% [P=0.117], high nuclear grade, 70% vs. 0% [P=0.001], total score 2-7 [mean 4.68] vs. 0-2 [mean 0.72] [P=0.001], high stage, 86% vs. 7% [P=0.0001]. Our findings indicate that a combination of multiple parameters can help differentiate between the two diseases. Two cases originally diagnosed as LPHL were re-assigned the diagnosis of THRLBCL

Grading of follicular lymphoma using flow cytometry

The treatment and prognosis of follicular lymphoma [FL] is dependant on the grade of the disease. In the World Health Organization classification of lymphoma, grading of FL into low grade [1 and 2] and high grade [3] is recommended. Grading of FL is possible in excision biopsy; histological grading is subjective and inconsistent Grading is extremely difficult in needle core biopsies and fine needle aspirates. We attempted to grade FL using flow cytometry [FCM] and CD 19/forward scatter. Cases of FL seen in our institution and submitted for FCM were evaluated for the percentage of cells detected beyond the 500-channel mark [on a 1024 scale] on a CD19/forward scatter dot plot. We hypothesized that these cells most likely represent centroblasts and their percentage would reflect the grade of the disease. Histological grading of the lymphoma on the open biopsies constituted the reference for FL grade. Thirty-six cases of FL, including 22 males and 14 females, ranging in age from 19 to 92 years [median, 42 years], were studied. There were 17 cases of low grade [grade 1; n=10 and grade 2; n=7] and 19 cases of high grade [grade 3] FL The percentage of cells identified beyond the 500-channel mark on CD19/forward scatter dot plot ranged from 0.12% to 12.55% [median, 4.9%] in low grade [grade 1 and 2] whereas the percentage of those cells in high grade FL ranged from 6.22% to 51.95% [median, 21%; p=0.00001]. Our findings suggest that using a CD19/forward scatter dot plot can help identify centroblasts in FL making grading possible on FCM, especially in small biopsies and fine needle aspirates

Biological markers in Helicobacter pylori-associated gastritis and carcinoma : the value of a scoring system

Background: Helicobacter pylori-associated gastritis has been linked to the pathogenesis of gastric adenocarcinoma [GA], especially when associated with intestinal metaplasia [IM] and atypia/dysplasia [A/D]. We examined p53 expression, ploidy and proliferative activity and assessed H. pylori infection in relationship to IM and/or A/D in cases of gastritis not associated with GA and in cases of GA

Methods: We examined 53 gastric biopsies from patients with gastritis not associated with GA, including patients with gastritis not associated with IM and/or A/D [n=35] and with gastritis associated with IM and/or A/D [n=21]. Thirty-six distal gastrectomy specimens from patients with GA constituted a third group of patients. A scoring system that encompassed the presence or absence of H. pylori, degree of gastritis, IM and/or A/D, p53, MIB-1 proliferative index [MPI] and ploidy was estimated in the cases of gastritis and in cancer-associated mucosa [CAM] and the adenocarcinoma from patients with GA

Results: Patients with GA had a higher median age than those with gastritis without IM and more were males [ratio, 2.2:1]. H. pylori was detected in 75% [40/53] of gastritis specimens and in 55% [20/36] of GA cases. There was a statistically significant difference between the incidence of gastritis without IM and/or A/D and CAM [P=0.01]. p53 expression was seen in 67% of cases [14/21] of gastritis with IM and/or A/D and in only 5% [2 cases] of gastritis without IM [P=0.0005]. A statistically significant difference in MPI was seen between CAM and GA [P=0.01] and gastritis without IM and/or A/D and gastritis with IM [P=0.004]. Cases of gastritis without IM and/or A/D had a median score of 8 while cases of gastritis with IM and/or A/D had a median score of 12 [P=0.0003]. CAM had a median score of 13, which was significantly different than gastritis without IM and/or A/D [P=0.0003]

Conclusion: The presence of IM and/or A/D can be used in H. pylori-associated gastritis as a starting point to further investigate high-risk lesions. Those showing p53 expression, high proliferative activity and aneuploidy require closer follow up and perhaps additional biopsies. Although aneuploidy is commonly seen in GA, its presence in cases of gastritis as an isolated finding should not indicate a high-risk lesion

Familial interstitial lung disease in five family members with different pathological staging

Reports on familial interstitial lung disease [ILD] are rare and all are indicative of high mortality. We report familial ILD in four siblings and their father. Lung biopsy on each patient revealed different stages of ILD in the form of usual interstitial pneumonia [UIP] in one child, desquamative interstitial pneumonia in 2 children, and non-specific interstitial pneumonitis with a predominance of inflammatory cells in another child. All four siblings presented with repeated chest infection, cyanosis and became oxygen dependent. Chloroquine was used in treating all 4 siblings with variable response. The child with UIP died from progressive disease while on treatment. The father was diagnosed at 40 years of age with ILD and extensive fibrosis, but did not respond to cyclophosphamide treatment. In conclusion, familial interstitial lung disease can present with different pathological stages in the same family members and the response to treatment depends on the degree of inflammation or fibrosis. The condition should be diagnosed early before it reaches an irreversible stage

B-and T-Lymphocyte distribution in benign and malignant lymphoepithelial lesions of the parotid gland: correlation with epstein-Barr virus expression and a proposed mechanism of malignant transformation

Epstein-Barr virus expression in malignant lympoepithelial lesions [LEL] of the parotid gland has been well established. The virus is occasionally expressed in benign, IEL, especially in immunocomprmised hosts. The pathogenesis of the disease as it related to virus expression and lymphocyte subsets has not been clearly defined. In this study, we attempted to identify B- and T-lymphocyte distribution in the lesions as it related to EBV expression in LEL[s] of the parotid gland. Formalin-fixed paraffin-embedded sections of 18 cases of LEL of the period gland were immunohistochemically tested for the distribution of B- and T-lymphocytes in the lesions, using the antibodies L-26 [CD 20] for B-lymphocytes and UCHL-1 [CD-45RO] for T-lymphocytes. The sections were also tested by in situ hybridization for EBV mRNA expression, using the EBER-1 probe specific for EBV-1 gene. The 18 lesions included seven malignant LEL, seven benign LEL and four benign lymphoepithelial cysts. All malignant LEL[s] showed a high and diffuse level of epithelial expression of EBV Mran. Of the 11 benign lesions, only one cases showed focal epithelial expression of EBV mRNA. This was a case of benign LEL in an HIV-positive male. All the benign lesions, except that expressing EBV mRNA, showed a T-/B-lympocyte ratio averaging 2:1. All cases expressing EBV mRNA, including the case of benign LEL in the HIV-positive patient, showed a T-/B-lymphocyte ratio averaging 1:3. Our findings suggest that a T-lymphocyte-mediated immune response may play an essential role in suppressing proliferation of EBV in benign LEL of the parotid gland. This immune mechanism may be significantly disturbed in the malignant lesions, leading to uncontrolled viral replication and carcinogenesis

Cell kinetics analysis of surgically resected non-small cell carcinoma of the lung using the AgNOR silver stain

Cell kinetics analysis of lung carcinoma using DNA flow cytometry has shown a significant correlation with the biological behavior of these neoplasms. Ploidy has shown a more significant association with aggressive behavior. The method may however not be available in all centers. Two counts of the A[g]NOR silver stain have been correlated with ploidy and proliferative activity [PA]. The first count, which is the mean number of A[g]NOR granules [mA[g]NOR], correlates with ploidy. The second count is the percentage of cells with >/= 5 A[g]NOR[s]/nucleus [pAGnor], reflects PA. We performed the A[g]NOR silver stain using the two abovementioned counts in 41 cases of surgically resected non-small cell carcinoma of the lung. The cases included 14 adenocarinomas, 24 squamous cell carcinoma, and three undifferentiated non-small cell carcinomas. Follow-up data were available on 36 of the patients, ranging from 10 to 31 months [median 18 months]. Thirteen of these patients [36%] developed progressive disease. Adenocarcinomas showed mA[g]NOR counts suggestive of aneuploidy [>/= 2.4] in nine of the 14 patents [64%] and 16 of the 24 squamous carcinomas [66%]. The adenocarciomas showed high pA[g]NOR counts [>/+8%] in eight of the 14 cases [57%], in contrast to 15 of the 24 squamous carcinomas [62%]. The A[g]NOR counts did not show any statistically significant correlation with tumor type, grade or stage of disease. The mA[g]NOR counts were aneuploid in all 13 progressive cases and in only 10 of the 23 stable cases [43%] [P=0.001]. The pA[g]NOR counts were high in 12 of the 13 cases that progressed [92%], in countrast to 10 of the 23 stable cases [43%] [P=0.01]. There is on significant evidence that squamous carcinoma of the lung may have a higher incidence of aneuploidy and high PA than adenocarcinoma. Our data also confirm previous data showing that aeuploid lung carcinomas have more aggressive behavior than diploid ones. This study also indicates that, despite the short-term follow-up data, the use of the A[g]NOR silver stain for cell kinetic analysis of non-small cell carcinoma of the lung may potentially provide useful predictive information on the biologic of lung carcinoma. Long-term follow-up may provide more significant information