Gallium-67 scan for distinguishing follicular hyperplasia from other AIDS-associated diseases in lymph nodes.

We have studied gallium-67 citrate scan (Ga-67) in the diagnosis of lymphadenopathy in patients with HIV-associated symptoms. Thirty HIV-infected patients with lymphadenopathy, fever and/or weight loss were evaluated with Ga-67. Lymph-node biopsy and/or needle aspirations were done in all patients. Twelve of 17 patients with grade 2 or 3 Ga-67 (uptake equal to or greater than that in the liver) had mycobacteriosis, three had lymphoma, one had Kaposi's sarcoma plus Castleman's disease and one had follicular hyperplasia. The three patients with grade 1 Ga-67 (uptake greater than that in soft tissue but less than that in the liver) had follicular hyperplasia. Of the 10 patients with grade 0 Ga-67 (less than or equal to that in soft tissue), nine had follicular hyperplasia and one had Kaposi's sarcoma. Sixteen of 17 patients with grade 2 or 3 Ga-67 versus one of 13 with Ga-67 grade 1 or 0 had diseases other than follicular hyperplasia (P less than 0.0001). Ga-67 may be a practical diagnostic tool in HIV-infected patients with lymphadenopathy and constitutional symptoms. A grade 1 or 0 Ga-67 suggests the presence of follicular hyperplasia, and lymph-node biopsy may be avoided unless Kaposi's sarcoma is suspected.

Lymphocytes with cerebriform nuclei in chronic B-cell lymphoproliferative diseases.

Two patients with chronic lymphoproliferative diseases, a splenic marginal zone lymphoma and hairy cell leukaemia variant, were reported. In both diseases a B-immunophenotype was demonstrated but a variable percentage of lymphoid cells (30 and 52%) showed a highly irregular nuclear outline, sometimes mimicking the nuclei of Sézary cells.

Lung cancer and pleural effusion. Clinical significance and study of pleural metastatic locations.

We reviewed results of 78 diagnostic thoracoscopic examinations of patients with lung cancer and homolateral pleural effusion. The study stresses the main locations of pleural metastasis in cases of lung cancer and correlates these data with the pleural spread from extrathoracic primary neoplasms. Also pointed out is the operability of the present series and the different behavior in pleural metastatic spread according to the histologic type with correlation between gross appearance of the effusion and the cytology.

Richter's syndrome after allogeneic stem cell transplantation for chronic lymphocytic leukaemia successfully treated by withdrawal of immunosuppression, and donor lymphocyte infusion.

Development of high-grade non-Hodgkin's lymphoma is a possible complication of chronic lymphocytic leukaemia/small lymphocytic lymphoma, known as Richter's syndrome (RS). Treatment for RS includes systemic chemotherapy and, recently, allogeneic stem cell transplantation (SCT). We describe a patient with B-chronic lymphocytic leukaemia who developed RS 4 months after allogeneic SCT from an HLA-identical sibling. The RS presented with systemic symptoms, lymphadenopathy, pancytopenia and serum lactate dehydrogenase elevation. The patient was treated with immunosuppressive drug withdrawal and a donor lymphocyte infusion (DLI) of 1 x 10(7) CD3/kg, leading to the disappearance of all symptoms and the attainment of complete donor chimerism. After 18 months of the therapeutic DLI, the patient continues in complete remission.

Autologous stem cell transplantation (ASCT) with immunologically purged progenitor cells in patients with advanced stage follicular lymphoma after early partial or complete remission: toxicity, follow-up of minimal residual disease and survival.

The role of autologous stem cell transplant (ASCT) in indolent lymphomas is a controversial issue. From 1994 to 1999, we performed ASCT with immunologically purged progenitor cells in 15 patients with advanced stage follicular lymphoma (FL) after early partial or complete remission. Results of the purging strategy and follow-up of minimal residual disease after transplant were analyzed with PCR amplification of bcl-2/IgH rearrangement for the t(14;18) translocation. A comparison of transplanted patients with a group of controls was carried out to evaluate differences in progression-free survival and overall survival. Eighty percent of patients received one chemotherapy regimen before ASCT and were in first remission. All the patients received cyclophosphamide plus hyperfractionated total body irradiation as the conditioning regimen. Nine patients were transplanted with bone marrow (BM) and six with peripheral blood progenitor cells (PBPC). Engraftment was delayed in one patient transplanted with BM. Two patients died during the transplant procedure. Ten of 12 evaluable patients were PCR positive in the BM for bcl-2 rearrangement at diagnosis. Six of them (60%) were still positive after chemotherapy, and one patient was transplanted with a positive hematopoietic product after purging. With a median follow-up of 27 months, six of eight evaluable patients still remain PCR negative in the BM. With a median follow-up of 4.7 years from diagnosis, progression-free survival was 83% (95% CI: 63-100). The risk of disease progression of non-transplanted patients was 19.2 times higher than that of transplanted patients (P = 0.01), but no differences were found in overall survival. Regarding patients in first remission, the risk of relapse was 12.6 times higher in non-transplanted than in transplanted patients (P = 0.04). This procedure seems to offer a good chance to achieve a PCR-negative state and prolonged freedom from recurrence. According to these results, prospective randomized trials are warranted.

Sézary syndrome and related variants of classic cutaneous T-cell lymphoma. A descriptive and prognostic clinicopathologic study of 29 cases.

Large series of patients with Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), have been reported infrequently because of its low incidence. Here we recorded several clinical, histopathological and immunophenotypical features of 29 cases of leukemic CTCL patients from four Dermatology Departments of Catalonia, Spain, and analyzed their prognostic value. Clinical data included sex, age, delay of SS diagnosis, previous diagnosis of lymphoma, B-symptoms, type of skin lesions, peripheral adenopathy, histologic evaluation of lymph node biopsy, visceral involvement, percentage of circulating Sézary cells, serum LDH and beta-2-microglobulin levels, first treatment and response, disease-free interval, further therapies and survival. Histopathological data examined were epidermotropism, depth and thickness of the infiltrate, cell size, adnexal involvement, presence of granuloma, eosinophils and plasma cells, mitotic rate. The percentage of CD45Ro, CD43, CD20, CD30 and CD8 positive dermal cells were also recorded. Survival showed a mean actuarial risk of 57% at 3 years and 38% at 5 years, with a median survival of 48 months. Analysis of actuarial survival demonstrated as following as features linked with a bad prognosis: fast evolution of the disease (from symptoms onset up to diagnosis) (p = 0.0274) raised levels of serum lactate dehydrogenase (p = 0.0379) and beta-2-microglobulin (p = 0.0151), the latter being the most important prognostic factor. In conclusion although SS had been traditionally considered as a low-grade lymphoma, the present study agrees with the recent classification rating SS as an aggressive type of CTCL with a poor prognosis. Our results show that some simple clinical and blood test data can be useful as prognostic indicators in this disease.

Occurrence of Hodgkin's disease and cutaneous B-cell lymphoma in the same patient: a report of two cases.

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) in the same patient is well known. The most frequent observation has been the development of large B cell lymphoma in patients affected with the nodular form of lymphocytic predominant HD. A less common situation is the development of NHL among patients successfully treated for HD. In such patients the second lymphoma has been thought to be related to the previous therapy or the immunodeficiency state that can accompany HD. Histologically, these NHL lymphomas often are intermediate to high grade and frequently extranodal. We report two patients successfully treated for HD who also developed NHL of the skin. Both patients presented with strikingly similar findings regarding to sex, age and subtype of HD. Clinical, histopathological and immunophenotypical findings were consistent with cutaneous low-grade B cell lymphoma of the marginal zone type. Both cases remain in complete remission of HD after standard therapy. In both patients the cutaneous lymphoma followed an indolent clinical course after a long follow-up period. This observation expands the spectrum of alterations possibly related to HD.

Peripheral neuropathy associated with angioimmunoblastic lymphadenopathy.

A 49-year-old man developed mononeuritis multiplex associated with angioimmunoblastic lymphadenopathy. The biopsy of the sural nerve revealed focal reduction of myelinated fibres and axonal degeneration, as well as perivascular inflammatory infiltrates composed of lymphocytes and plasma cells, exhibiting policlonal immunoglobulin expression, proliferation of blood vessels, thickening of the vessel wall and endothelial hyperplasia. These latter changes are similar to those commonly encountered in the lymph nodes, as well as in other organs, in patients suffering from angioimmunoblastic lymphadenopathy.

[Peripheral T-cell lymphomas without primary skin involvement. An anatomicoclinical study of 29 consecutive cases]. / Linfomas T periféricos sin afectación cutánea primaria. Estudio anatomoclínico de 29 casos consecutivos.

BACKGROUND: To analyze peripheral non-cutaneous T-cell lymphomas (NC-TCL) and to test the significance of the IPI. PATIENTS AND METHODS: Twenty-nine consecutive patients diagnosed with NC-TCL according to the REAL classification. RESULTS: At diagnosis were common: B symptoms (21%), stage III/IV (55%), high LDH level (55%) and extranodal involvement (79%). Twelve (48%) patients achieved complete remission. The IPI identified groups of patients with different response to therapy and survival. CONCLUSIONS: NC-TCL with high or high-intermediate IPI had a short survival if treated with CHOP.

Clinical Characteristics and Risk of Relapse for Patients with Stage I-II Diffuse Large B-cell Lymphoma Treated in First Line with Immunochemotherapy.

Diffuse large b-cell lymphoma (DLBCL) is an aggressive and potentially curable lymphoma that presents itself as stage I-II in 30% of all cases. It is known that in these localized stages, 15-20% of patients treated without rituximab eventually relapse, but less data exist regarding rituximab era. We have analyzed clinico-pathological features and risk of relapse in 98 patients with I-II stage DLBCL in complete response (CR) or unconfirmed CR (CRu) after first-line treatment consisting of immunochemotherapy. Twelve patients (12.2%) eventually relapsed. Late relapse, more than two years after diagnosis, occurred in three patients, and early relapse, less than two years after diagnosis, was documented in nine patients. Median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse. The second CR rate obtained was similar in the late and in early relapsing patients, being 33% versus 44% (p = 0.072), respectively. Three-year overall survival (OS) was 22% for early relapsing patients and 33% for late relapsing patients (p = 0.65). In conclusion, patients who are diagnosed with stage I-II DLBCL and achieve a CR/CRu with first line immunochemotherapy have a good prognosis. However, a proportion of patients relapse, and this is less frequent in patients treated with first line with immunochemotherapy. These patients have a poor prognosis.

Angiotropic malignant melanoma. Report of two cases.

Two cases of malignant melanoma are described that showed focal perineural invasion and exhibited striking tropism for small and medium-sized vessels, primarily veins. The melanoma cells proliferated within the vessel walls, expanding and replacing the muscle layer but sparing the endothelia. Intravascular invasion was not seen. Immunohistochemical studies confirmed the pattern of growth within vessel walls and the integrity of their endothelia. In one of the cases, similar vascular tropism was encountered in a capsular vein from a regional lymph node. We propose the term "angiotropic malignant melanoma" for this phenomenon and suggest that angiotropism may be a rare mechanism for melanoma spread and progression.

Necrotizing sialometaplasia (adenometaplasia) of the trachea.

Necrotizing sialometaplasia is a benign condition first described in minor salivary glands of the soft palate with morphological changes which can be misinterpreted as squamous-cell carcinoma. Similar lesions have been subsequently reported in other locations including major salivary glands, lip, breast and skin (the term syringometaplasia has been applied for the latter). We report three cases of such a process involving submucosal glands in the trachea following prolonged translaryngeal intubation.

Herpetiform eruption with leukocytoclasis: a distinctive clinico-pathological variety of erythema multiforme.

Six patients are described who experienced a prodromal period suggesting an infective process, followed by a distinctive polymorphous cutaneous eruption. The most striking lesion, present in all of them and giving the eruption a distinctive herpetiform appearance, included closely grouped vesicles resting on an erythematous base. Histopathological examination of these lesions showed features of dermal and epidermal types of erythema multiforme but with prominent leukocytoclasis. We suggest that the clinico-pathological picture of our patients may be considered a distinctive clinico-pathological variety of erythema multiforme.

Sarcomatoid renal cell carcinoma: a case of spontaneous regression of metastases.

The spontaneous regression of metastases in renal cell carcinoma is usually associated with the clear cell carcinoma histologic type. We report a case of spontaneous regression in a man with lung metastases from a sarcomatoid renal cell carcinoma variant. At present, 1 year after regression was first evident, the patient remains in remission.

Tuberculosis-associated hemophagocytic syndrome. A systemic process.

Virus-associated hemophagocytic syndrome has been recently identified as a benign, reactive histiocytic proliferation distinct from Rappaport's malignant hystiocytosis. Other etiologic agents, including different bacteria, have also been identified. Three autopsy cases of hemophagocytic syndrome associated to acute tuberculous sepsis are presented. Benign histiocytic proliferation with striking hemophagocytosis was present in a disseminated, multisystemic pattern in all three cases. A relationship between systemic histiocytic proliferation and an anergic status in these patients is suggested.

Zoledronate-induced remission of acute panmyelosis with myelofibrosis.

Acute panmyelosis with myelofibrosis is a rare and aggressive form of acute myeloid leukemia. We describe a new case with a huge proliferation of megakaryocytes, blast cells and reticulin fibers. The patient was treated with zoledronate, a third-generation bisphosphonate, and a gradual recovery from pancytopenia was observed. A new bone marrow biopsy performed 4 months later showed a surprising disappearance of the leukemic infiltration. Ten months after the diagnosis, the patient is still in healthy condition. This may support the recently described anti-tumor activity of zoledronate.

Bone marrow involvement in lymphoblastic lymphoma and small non-cleaved cell lymphoma: the role of trephine biopsy.

Trephine biopsy (TB) combined with bone marrow aspiration (BMA) is the most common method for evaluating bone marrow (BM) involvement in non-Hodgkin's lymphomas. Nevertheless, the role of TB in high-grade lymphomas remains controversial. We reviewed the results of 42 consecutive BMAs and TBs performed simultaneously in 29 patients with lymphoblastic lymphoma (LL) and small, non-cleaved cell lymphoma (SNCL). In LL, 8M involvement was documented in 35.4% of the cases by BMA and 22.5% of the cases by TB. In SNCL it was documented in 45.4% of the cases by BMA and 36.3% by TB. There were no statistically significant differences (p > 0.05) in the rates of BM involvement found by TB or BMA in the two types of lymphoma, although BMA appeared to be more sensitive than TB. These observations suggest that routine TB may not be necessary in assessing BM involvement in patients with LL and SNCL.

Cardiac involvement and molecular staging in a fatal case of mycosis fungoides.

Polymerase chain reaction (PCR) amplification of T-cell receptor-gamma gene rearrangement was used for molecular staging in a case of primary cutaneous T-cell lymphoma (CTCL) with fatal evolution. Although initial evaluation was negative for systemic involvement, the patient died due to heart failure. Autopsy findings revealed lymphomatous myocardial infiltration, but other tissues and organs examined, including lymph nodes, liver, spleen, lung and bone marrow, appeared to be free of disease. Molecular analysis from frozen samples obtained during the initial evaluation, as well as paraffin-embedded material obtained during autopsy, revealed the presence of clonal rearranged bands in all tissues examined except the bone marrow. Subsequent hybridization of PCR products with a tumour-specific oligoprobe confirmed the PCR results, suggesting widespread dissemination of the lymphomatous process. The use of molecular analysis can add significant information about the extent of disease in patients with CTCL and may be helpful in the establishment of therapeutic options.

Genotypic analysis of cutaneous T-cell lymphoma: a comparative study of Southern blot analysis with polymerase chain reaction amplification of the T-cell receptor-gamma gene.

The diagnosis of early cutaneous T-cell lymphoma (CTCL) is a difficult point in dermatology. Recently, Southern blot analysis (SBA) and polymerase chain reaction (PCR) have been used to detect clonality in initial lesions in which clinical and histological findings are unspecific. Forty-one samples from 25 patients with CTCL were investigated for the presence of T-cell receptor-gamma gene rearrangement using a nested PCR technique and analysed by polyacrylamide gel electrophoresis (PAGE). Conventional SBA was also performed on 28 samples from 20 of these patients. In addition, 20 samples corresponding to patients with large plaque parapsoriasis (LPP), cutaneous B-cell lymphoma (CBCL) and eczema were analysed by PCR in the same way as were the CTCL specimens. Most of the CTCL specimens (81%) showed clonality on PCR analysis. Among patients with mycosis fungoides, 71% of initial patch lesions and 100% of plaques and tumours showed clonal disease. Clonality could be detected in three of four histologically negative post-treatment lesions. Clonal rearrangement was detected in one of three patients with LPP and in three of 10 patients with CBCL. None of the samples corresponding to patients with eczema showed positive results. SBA was significantly less sensitive than PCR in detecting clonality in CTCL patients (42% among early disease and 60% among advanced cases). The results indicate that this PCR/PAGE technique is a reliable and useful method for the detection of clonality in early skin lesions of CTCL patients and probably in the identification of silent extracutaneous involvement.