T-cell/histiocyte-rich B-cell lymphoma: Clinical presentation, management and prognostic factors: report on 61 patients and review of literature.

T-cell/histiocyte-rich B-cell lymphoma (TC/HRBCL) is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with characteristic morphologic and immunophenotypic features, often misdiagnosed as Hodgkin's lymphoma and peripheral T-cell lymphoma. Few and conflicting clinical data are available in the literature addressing optimal treatment, prognosis and outcome. We retrospectively reviewed all patients diagnosed and managed at our institution between 1995 and 2004 diagnosed with T-cell-rich-B-cell lymphoma by WHO criteria. Sixty-one patients were identified. Initial pathology was incorrect in 82% of referred cases. The median age was 30 years. Seventy-one patients were males. Stage distribution was I - II in 21 patients, and III - IV in 40. Fifty-two percent of patients (32) had splenic involvement and thirty-seven patients (61%) presented with extranodal disease (22 >or= 2 sites). The International Prognostic Index (IPI) score was >or=2 in 62% of patients. All 59 newly diagnosed TC/HRBCL patients were treated with CHOP or R-CHOP combination chemotherapy +/- radiation therapy. The overall response rate was 85% and nine patients progressed on therapy. Fourteen patients relapsed with a median time of relapse of 6 months (range, 2 - 28). At a median follow-up of 22 months (range 1 - 132); 32 patients (52%) are alive with no evidence of disease. The 5-year overall survival and event free survival rates were 46% and 39% respectively. To conclude, TC/HRBCL is difficult to recognize without immunohistochemistry. It has an aggressive course and poor outcome; with most of patients presenting with advanced disease stage together with high IPI score. Treatment outcome seems to be similar to IPI matched DLBCL counterpart.

Grading of follicular lymphoma using flow cytometry.

BACKGROUND: 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 CD19/ forward scatter. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Cytomorphologic differentiation of Hodgkin's lymphoma and Ki-1+ anaplastic large cell lymphoma in fine needle aspirates.

OBJECTIVE: To cytomorphologically differentiate Hodgkin's lymphoma (HL) from Ki-1+ anaplastic large cell lymphoma (ALCL) in fine needle aspirates. STUDY DESIGN: We blindly reviewed 63 fine needle aspiration (FNA) smears from histologically and immunophenotypically proven cases of ALCL (n = 15) and HL (n = 48). The smears were reviewed for the following criteria: (1) estimated percentages of abnormal cells, (2) pattern of the smears (polymorphous vs. dimorphous), and (3) presence or absence of multilobated cells. RESULTS: All cases were phenotyped by immunohistochemistry for CD3, CD15, CD20, CD30 and CD45, with flow cytometric immunophenotpyping in 41 cases. Flow cytometric phenotyping was not successful in any of the cases. The smears were polymorphous in all 15 cases of ALCL and in 1 case of HL (2%). The percentage of abnormal cells ranged from 10% to 90% in cases of ALCL (median, 30%) whereas it ranged from 1% to 25% in HL (median 3%; P = .0003). Three cases of HL showed abnormal cells constituting > or = 20% of the smears. They were all grade 2 disease. Multilobated cells were identified in 14 of the 15 cases of ALCL (93%) and in 3 of the 48 cases of HL (6.25%; P = .0008). CONCLUSION: Our findings indicate that the differentiation of ALCL from HL can be achieved in FNA smears through identification of abnormal cells representing > 30% of the population, a spectrum of abnormal cells and the presence of multilobated nuclei. Rare cases of grade 2 HL may be difficult to differentiate from ALCL.

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). CONCLUSIONS: 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms.

OBJECTIVES: To evaluate the changing management of sporadic renal angiomyolipoma and renal angiomyolipoma associated with the tuberous sclerosis complex (TSC) during the past 16 years. METHODS: We retrospectively reviewed the charts of 60 patients with angiomyolipoma seen at our institutions. RESULTS: The median age at presentation was 45 years (range 7-78). The presentation was pain in 30 patients and hematuria in 13; it was incidentally discovered in 17 patients. Of the 60 patients, 43 were females. TSC was present in 14 patients. The median tumor size was 4 cm (range 0.3-40, mean 6.5 +/- 1.1). Of the 60 patients, 31 were followed up expectantly. Surgery or intervention was needed for 29 patients to control hemorrhage or relieve pain or because of the suspicion of malignancy. Of these 29 patients, 12 underwent nephrectomy, 11 partial nephrectomy, and 6 embolization. The patients treated for hemorrhage had a median tumor diameter of 11 cm (range 2-21). Patients were followed up for a mean of 39.3 +/- 5.4 months. The lesions grew an average of 4.7 +/- 3.4 cm for TSC tumors and 0.6 +/- 0.2 cm for sporadic angiomyolipoma tumors. None of the patients developed renal impairment. Patients with TSC presented at a younger age, had larger and bilateral lesions, and were more symptomatic during follow-up. In the past 6 years, a significant trend was seen toward finding tumors in asymptomatic patients and toward the use of conservative or interventional (embolization) treatment. CONCLUSIONS: Renal angiomyolipoma has a slow growth rate. The preservation of renal function was noted in all our patients. A recent shift was noted toward finding smaller tumors in asymptomatic patients and the use of conservative and interventional treatment.

Crural tunica albuginea autograft for corporoplasty: an experimental animal study of hemodynamic, histopathological, and molecular effects in the long term.

INTRODUCTION: Correction of penile deformity caused by Peyronie's disease by a variety of grafts varies in success. A long-term follow-up shows a significant number of graft scarring and erectile dysfunction. The clinical success of autologous crural tunica albuginea graft (TAG) has not resulted in wide application. AIM: To identify in healthy baboons the limitations and merits of autologous crural TAG over 1 year in a way difficult to pursue in humans. METHODS: Under general anesthesia, eight sexually active adult baboons underwent pharmacological cavernosometry (CM) and cavernosography. TAG from crus was implanted in the distal penile shaft. After 6 months, six animals were reevaluated and two were sacrificed, and the penises were excised. After 1 year, the remaining six animals were evaluated and sacrificed. The TAG and underlying corpus cavernosum (CC) were examined histologically and by Western blot analysis for nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms, and transforming growth factor-beta1 (TGF-beta1). MAIN OUTCOME MEASURES: Sexual activity, CM, cavernosography, histopathology, and Western blot analysis. RESULTS: All animals resumed normal sexual activity 1 month postsurgery. Cavernous pressure was comparable before, at 6 months, and 1 year after surgery. A cavernovenous insufficiency developed in four animals at 6 months, and ceased in two at 1 year. Penile angulation (<20 degrees) was seen in three animals at 6 months, and an additional two at 1 year. Histologically, TAG was indistinguishable from the adjacent tunica with no fibrosis. In CC, iNOS and nNOS decreased at 1 year, whereas there was no change in TGF-beta1 levels. In TAG, there was no significant change in TGF-beta1 and eNOS levels, but there was a significant decrease in iNOS at 1 year. CONCLUSION: Autologous free TAG is associated with normal sexual activity, minimal hemodynamic changes, excellent histological outcome, and no rise in iNOS or TGF-beta1. However, cavernovenous insufficiency, mild penile angulation, and decreased nNOS persisted at 1 year.

Outcome of penile cancer in circumcised men.

PURPOSE: We previously reported on a group of patients with post-circumcision carcinoma of the penis. We now study the long-term outcome of these patients. MATERIALS AND METHODS: We retrospectively reviewed the available charts of 22 patients presenting between October 1979 and May 2000. RESULTS: Of 22 patients 18 underwent ritual circumcision with extensive scar development. Median age at diagnosis was 62.4 years. The penile lesion was dorsal and proximally located in 15 patients. Median delay before diagnosis was 12 months. Clinically 14 patients had stage T1-T2 disease, with 13 having no lymph node involvement and none with distant metastasis, 8 patients had stage T3-T4 disease. A total of 15 patients were treated surgically with total penectomy (10) or conservative local excision (5), inguinal lymph node dissection (9) and subsequent penile reconstruction (3). Pathological staging in 15 patients revealed 10 patients with stage T1 and in 8 patients with lymph node dissection none had nodal metastasis. Histopathological classification was 20 squamous cell carcinoma, 1 sarcoma and 1 verrucous carcinoma. Six patients refused surgery and 1 was referred for palliation. Median followup was 14.5 months and median survival was 14.5 months. The 3-year survival was 42% for stage T1-T2 and 13% for T3-T4 (p = 0.0052). Median survival for the surgical group was 34 months whereas for nonsurgical group was 3 months (p = 0.0016). Recurrence-free survival in the surgical group was 50%. CONCLUSIONS: Penile carcinoma in circumcised men is a distinct disease commonly following nonclassic vigorous circumcision. Delayed diagnosis and deferring surgical treatment are associated with increased mortality.

The impact of the World Health Organization classification and clonality assessment of posttransplant lymphoproliferative disorders on disease management.

CONTEXT: The World Health Organization classification of posttransplant lymphoproliferative disorders divides them into 4 main categories. OBJECTIVE: To classify cases of posttransplant lymphoproliferative disorders diagnosed in our institution according to the World Health Organization scheme and correlate the classification and clonality with clinical data. DESIGN: Cases of posttransplant lymphoproliferative disorders were reviewed. They were classified according to the World Health Organization scheme. Clonality was determined by flow cytometry and/or polymerase chain reaction. Patients' charts were reviewed. RESULTS: Thirty-one cases were identified. Median age was 33 years. There were 19 cases of kidney, 8 cases of liver, and 4 cases of bone marrow transplant. Immunosuppression consisted of cyclosporin A and prednisone (N = 24) or FK506 and prednisone (N = 7). Twenty cases (63%) were World Health Organization type 3, 7 cases (23%) type 2, 3 cases (6.4%) type 1, and 1 case type 4 posttransplant lymphoproliferative disorder. Ten patients received chemotherapy, 20 patients had reduction of immunosuppression, and 1 had no treatment. Follow-up was available on 25 patients. Seven (43.75%) of 16 with type 3 lesions with available follow-up died of their disease. Five of these patients received reduction of immunosuppression alone. Only 2 of 9 patients with type 3 disease who received chemotherapy died of disease. Two patients with type 2 disease died of unrelated causes. One patient is alive with disease; the remaining patients with types 1 and 2 disease are alive with no disease. CONCLUSIONS: The World Health Organization classification of posttransplant lymphoproliferative disorders is valuable in the identification of subtypes. It helps identify early lesions (1 and 2) requiring reduction of immunosuppression and type 3 disease, which requires chemotherapy from the outset.

A study comparing different approaches in managing neck nodes in early carcinoma of the tongue.

OBJECTIVE: To evaluate elective neck treatment in patients with early stage (T1-2 negative neck node [N0]) squamous cell carcinoma of the oral tongue. METHODS: The medical records of all patients with early stage (T1-2 N0) of oral tongue cancer at the King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, between January 1980 and December 1997, were identified and retrospectively reviewed. RESULTS: Our cohort consisted of 93 patients: 45 males and 48 females, with a median age of 60 years. All patients received treatment with curative intent. Partial glossectomy was carried out, except for 8 patients who underwent tongue brachytherapy. The neck was observed in 29 patients, 36 were treated by modified neck dissection, and 28 by elective neck irradiation. With a median follow-up of 62 months, 29 patients had documented neck node recurrence. Ninety six percent (28/29) of recurrences occurred within 22 months from treatment completion. The 5 year actuarial event free survival with regard to nodal relapse in observed was 59%, dissected was 79% and irradiated neck was 63%. Our results showed a trend toward better neck node control in patients managed by elective neck dissection compared to those observed (p=0.07) or receiving elective neck irradiation (p=0.18). Tumor thickness of more than 10 mm was associated with increased risk of nodal relapse (p=0.0004). Neck node recurrence has a poor prognosis with a 5 year disease specific survival of 16%. CONCLUSION: A trend for higher neck control was observed after neck dissection in patients with T1-2 N0 squamous cell carcinoma of the oral tongue. Elective neck dissection should be considered particularly for patients with tumor thickness of more than 10 mm.