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Uterine leiomyoma with massive lymphocytic infiltration simulating malignant lymphoma. A case report with immunohistochemical study showing that the infiltrating lymphocytes are cytotoxic T cells.

Uterine leiomyoma with massive lymphoid infiltration is very rare and may simulate malignant lymphoma. To the best of our knowledge, this is the first description of such a lesion occurring in an Oriental, and the ninth case in the English literature. A 50-year-old Taiwanese woman had urinary frequency and nocturia because of a uterine myoma. The myomectomy specimen was identified as a well-defined tumor, 6.5-cm in diameter, the cut surface of which was pale, white and whorled. A massive lymphocytic infiltration accompanied by plasma cells and histiocytes was noted in the leiomyoma but not in the surrounding non-neoplastic myometrial fibers. Most infiltrating lymphocytes were positive for CD3 and T cell intracellular antigen-1, a cytotoxic marker. The postoperative course was uneventful, and the urinary symptoms improved within a 6-month follow-up period.

Adult↗

Pulmonary alveolar proteinosis in a patient with acute lymphoid leukemia regression after G-CSF therapy.

Pulmonary alveolar proteinosis (PAP) is the intra-alveolar accumulation of periodic-acid schiff (PAS) positive material. PAP is one of the underrecognized causes of pulmonary infiltrates in patients with hematologic malignancies. Here, we present a patient with acute lymphoid leukemia (ALL) in first remission that developed fever and diffuse pulmonary infiltrates during the neutropenic stage of consolidation chemotherapy. The histopathologic examination of bronchoalveolar lavage (BAL) fluid and transbronchial biopsy specimen demonstrated the presence of PAS-positive eosinophilic material. Empirical antibiotherapy and granulocyte-colony stimulating factor (G-CSF) were given. After the correction of neutropenia with G-CSF, the patient's fever disappeared, acute phase reactants decreased, pulmonary infiltrates resolved. We present this case because it was the first patient in whom the correction of neutropenia with G-CSF was followed by resolution of PAP.

Female↗

Leukemia cutis with prominent giant cell reaction.

We present a case of leukemia cutis associated with a prominent giant cell component. This lesion was initially diagnosed as chronic granulomatous inflammation 1 year before the definitive diagnosis of leukemia cutis was made. Skin biopsy specimens showed numerous Langhans-type giant cells occurring singly and as poorly formed granulomas. However, the majority of the infiltrate consisted of immature myeloid cells, positive for chloroacetate esterase, lysozyme, and CD 68. Subsequent peripheral blood and bone marrow examinations confirmed the progression of the disease to acute myeloid leukemia.

Aged↗

Bone marrow angiogenesis and proliferation in B-cell chronic lymphocytic leukemia.

OBJECTIVE: To assess angiogenesis and the proliferative activity of bone marrow in patients with chronic lymphocytic leukemia (CLL) in relation to the bone marrow infiltration pattern. STUDY DESIGN: Bone marrow samples were obtained by trephine biopsy from 46 patients with B-cell CLL (B-CLL). Infiltration pattern was diffuse in 20 patients and nondiffuse--i.e., nodular, interstitial or mixed--in the remaining 26 patients. Ten normal bone marrow samples were used as a control group. Studies were carried out by immunohistochemical staining of paraffin-embedded bone marrow samples. Angiogenesis was assessed in the zones of highest vascular density (hot spots), visualized by the expression of endothelial antigen CD34 and expressed as a number of microvessels per high-powerfield (hpf) (final magnification, 400x). Proliferative activity was estimated by the expression of nuclear protein Ki-67, cyclin A and mean number of nucleolar organizer regions (AgNORs). RESULTS: Microvessel density was higher in B-CLL marrow than in normal marrow (30.1 and 16.44 per hpf, respectively) and was higher in the diffuse than nondiffuse pattern (33.6 and 27.5 per hpf, respectively). B-CLL bone marrow also showed higher proliferative activity, as assessed by mean number of AgNORs, than did normal marrow (1.52 and 1.25, respectively) and a higher mean percentage of cyclin A-positive cells (7.5 and 6.8, respectively). In contrast, mean Ki-67 expression was similar in B-CLL and the control group. Mean AgNORs number, Ki-67 and cyclin A-positive cell percentage were significantly higher in B-CLL marrow with a diffuse as compared to nondiffuse involvement pattern (AgNORs, 1.75 and 1.35; cyclin A, 9.27% and 3.95%; Ki-67, 34.9% and 23.3%, respectively). CONCLUSION: Our results indicate enhancement of bone marrow angiogenesis in B-CLL and a relationship between microvessel density and the bone marrow infiltration pattern. The study points also to a possible relationship between the bone marrow infiltration pattern and proliferative activity of bone marrow cells.

Adult↗

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r = 0.73, P = 0.001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78.33 +/- 23.86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66.12 +/- 66.17) than patients without extramedullary organ infiltration (median 17.56 +/- 19.29; P < 0.001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102.74 +/- 92.13; P < 0.003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Antibodies, Monoclonal↗

Epstein-Barr virus-associated T-cell acute lymphoblastic leukaemia.

Epstein-Barr virus (EBV) is frequently detected in haematological malignancies, including Burkitt's lymphomas/leukaemias, Hodgkin's diseases and non-Hodgkin's lymphomas. However, immature T-cell malignancies associated with EBV have not been reported previously. We report a patient with T-cell acute lymphoblastic leukaemia (T-ALL), whose leukaemic cells had EBV, confirmed by Southern blotting and in situ hybridization. The EBV existed in episomal form and was detected in most leukaemic cells, but not in bystander normal B-cells. The leukaemic cells, massively infiltrated into the liver and spleen, were resistant to chemotherapy. EBV might be associated with tumorigenesis of T-ALL, and characteristic clinical features of the patient.

Adult↗

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars.

BACKGROUND: Cutaneous lymphoid infiltrates at sites of herpes zoster scars in patients with B-cell chronic lymphocytic leukemia (B-CLL) often are diagnosed as benign lymphoid hyperplasia ("pseudolymphomas"). The histologic and immunophenotypic features of these lesions are not well characterized. Appearance of skin lesions in B-CLL patients is considered a poor prognostic sign. METHOD: Eight punch biopsies from five patients (three males, two females; mean age, 66.7 years) affected by B-CLL and presenting with lesions at sites of previous herpes simplex (upper lip, one patient) or herpes zoster (trunk, four patients; forehead, one patient) infections were included in the study. Histologic examination was performed on routine sections stained with hematoxylin and eosin and Giemsa. Immunohistologic stainings were performed with a standard three-step immunoperoxidase technique on formalin fixed, paraffin embedded tissue sections. RESULTS: Specific cutaneous infiltrates of B-CLL were diagnosed histopathologically and immunophenotypically in eight biopsies from all five patients. Clinically, patients presented with erythematous papules or plaques confined to the area of previous herpes virus eruptions. Histopathologic features in most cases were characterized by a variably dense perivascular and periadnexal infiltrate of small hyperchromatic lymphocytes throughout the entire dermis, reaching the subcutaneous fat. In one case, a dense, diffuse infiltrate involving the entire dermis was observed. A granulomatous reaction with presence of epithelioid and multinucleated giant cells was a prominent feature in four biopsies from three patients. Light areas containing large lymphoid cells with features of prolymphocytes and paraimmunoblasts (so-called "proliferation centers") could be observed only in the case characterized by a diffuse infiltrate. Immunohistology revealed an aberrant CD20+/CD43+ phenotype of neoplastic B cells, which is not found in normal B lymphocytes (CD20+/CD43-). Reactive T lymphocytes were present in all lesions and had a normal CD20-/CD43+/CD45Ro+ phenotype. At the time of this writing, four patients were alive without signs of skin disease after a mean follow-up of 58.5 months, and one patient died of B-CLL 24 months after the cutaneous eruption. CONCLUSIONS: Specific cutaneous infiltrates of B-CLL are not uncommon at sites of herpes virus scars. The diagnosis can be confirmed by histopathologic and immunophenotypic criteria. The prognosis is better than previously reported.

Aged↗

Disseminated Mycobacterium kansasii infection with pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.

A 64-year-old woman with chronic myelogenous leukemia (CML) was admitted due to prolonged fever and lung infiltrates. An open lung biopsy was required to make the diagnosis of pulmonary alveolar proteinosis (PAP) and infection with Mycobacterium kansasii. She was treated successfully with combined antimycobacterial therapy for 14 months. However, the leukemia progressed and the patient developed recurrent bilateral lung infiltrates. Blood and bronchoalveolar fluid cultures yielded growth of Acinetobacter. She died shortly thereafter due to septic shock. The relationship between M. kansasii infection, PAP, and abnormal host defense in CML is discussed.

Fatal Outcome↗

Transient leukaemia cutis in chronic lymphocytic leukaemia.

Leukaemia cutis arises from cutaneous infiltration by neoplastic leukocytes or their precursors. Recent evidence suggests that this sign does not necessarily herald a poor prognosis. We describe a 72-year-old woman with B-cell chronic lymphatic leukaemia who developed a papular eruption of her breast at the site of a recent herpetic eruption. Histology and immunostaining showed a dense dermal B-cell infiltrate in keeping with leukaemia cutis. The papules cleared in 6 months without treatment, leaving atrophic scars. The histological features and possible aetiological mechanisms of post-herpetic papular eruptions in chronic lymphatic leukaemia are reviewed.

Aged↗

Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients.

To evaluate the relative merits and prognostic value of bone marrow aspirate and bone marrow biopsy in the assessment of bone marrow infiltration in B-cell chronic lymphocytic leukaemia (CLL), two observers independently reviewed the percentage of lymphocytes in bone marrow aspirate (lymphocytic infiltration, LI) and the bone marrow histological pattern (BMP) in 258 patients. The inter-observer reproducibility and agreement was higher for BMP than for LI. BMP was an independent prognostic factor for survival in the whole series, whereas LI only had independent predictive value in stage A patients. In the entire series, disease progression was predicted by either BMP and LI, whereas in stage A patients only by BMP. Regarding low-risk CLL (smouldering CLL or A"1 substage), BMP led to a more reproducible identification of these clinical forms than LI. In conclusion, although both BMP and LI are of value to estimate bone marrow infiltration in CLL and to predict the outcome of the disease, BMP is more reliable and reproducible than LI.

Aged↗

Otological manifestations of acute leukaemia: report of two cases and review of literature.

Otological manifestations exceptionally reveal acute leukaemia, whereas leukaemic infiltration of any tissue is frequent at postmortem examination. We present two cases of acute myeloblastic leukaemia revealed by a loss of hearing due to a middle-ear leukaemic infiltration. The characteristics of such a clinical and radiological finding are emphasized. It is suggested that middle and inner ear can be a 'sanctuary' localization, which might sometimes require radiation therapy to achieve durable and complete remission.

Adult↗

Malignant infiltration of peripheral nerves in the course of acute myelomonoblastic leukaemia: neuropathological study of two cases.

Two patients suffering from acute myelomonoblastic leukaemia developed clinical evidence of peripheral nerve involvement. In both cases, a peripheral nerve biopsy revealed endoneurial cellular infiltrates which were identified as leukaemic cells by immunocytochemistry. Ultrastructural studies showed mainly axonal damage. Moreover, in one patient, a few features of active demyelination were also observed.

Action Potentials↗

Antitumor activity of the angiogenesis inhibitor TNP-470 on murine lymphoma/leukemia cells in vivo and in vitro.

OBJECTIVE: The aim of this study was to evaluate the effects of an angiogenesis inhibitor in a non-immunocompromised setting in which transplanted tumor cells home and expand in a manner mimicking the original tumor in the donor. We used a novel animal model for T-cell lymphoma/leukemia (TLL) to test the antitumor effect of TNP-470, a well-established angiogenesis inhibitor. MATERIALS AND METHODS: Cells from spontaneously arisen TLL tumors were transferred to syngenic recipients. The mice were treated with TNP-470 (30 mg/kg) or vehicle every other day for 2 weeks. Mice were sacrificed on day 15 after transfer, and body and organ weights were measured. Cell cycle and morphologic analysis was performed on cells and/or sections from selected organs. The cytotoxic effect of TNP-470 was assayed in vitro using the TLL-M and HL-60 cell lines. RESULTS: TNP-470 treatment significantly reduced total tumor load and tumor mass in specific organs infiltrated with lymphoma/leukemia. This was associated with an increased apoptosis in these organs. We also observed side effects of TNP-470 not previously reported, such as diminished extramedullary erythropoiesis and disrupted liver morphology. In vitro TLL-M cells were resistant to cytotoxic effects of moderate doses of TNP-470. CONCLUSIONS: TNP-470 treatment has a beneficial effect on tumor load in the TLL transfer model, most likely caused by the antiangiogenic effect of TNP-470. This is supported by the observation of increased apoptosis in infiltrated organs. The TLL transfer model is well suited for further studies of combinations with TNP-470 or other angiogenesis inhibitors and cytotoxic drugs.

Angiogenesis Inhibitors↗

Physiological features of pericardial constriction in the absence of pericardial disease.

To sustain a clinical diagnosis of constriction it is classically held that the fibrous pericardium must be thickened and adherent to the surface of the heart. A case is presented in which leukaemic infiltration of the fat overlying the myocardium resulted in the physiological features of constriction, although all layers of the pericardium itself were normal. Constriction is thus a physiological diagnosis; it may develop in the absence of the classical anatomical findings.

Aged↗

[The expression and clinical significance of stromal cell-derived factor-1 and CXCR4 in acute leukemia and malignant lymphoma].

OBJECTIVE: To analyze the expression of stromal cell derived factor-1 (SDF-1) and its functional chemokine receptor CXCR4 in patients with acute leukemia and malignant lymphoma. METHODS: CXCR4 expressed on the membrane surface of marrow mononuclear cells was enumerated with 3-color flow cytometry. The serum level of SDF-1 was determined with ELISA assay. RESULTS: The expression of SDF-1 and CXCR4 in acute leukemia for ALL group, the expression of SDF-1 and CXCR4 is (7115.8 +/- 946.5) ng/L and (77.2 +/- 9.7)%; for ANLL group, the expression is (4642.2 +/- 1146.8) ng/L, (38.9 +/- 11.0)% and malignant lymphoma for HD group, the expression of SDF-1 and CXCR4 is (3728.9 +/- 690.9) ng/L and (9.2 +/- 2.7)%; for NHL group, the expression is (4442.1 +/- 1073.0) ng/L and (8.5 +/- 2.4)% patients were higher than that in controls the expression of SDF-1 and CXCR4 is (2369.3 +/- 966.5) ng/L and (2.7 +/- 1.5)% (P < 0.01). In the leukemia group, the patients with extra-marrow infiltration have higher expression of SDF-1/CXCR4 than those without and the patients; in the lymphoma group. CONCLUSIONS: The high expression of SDF-1 and CXCR4 is somewhat correlated with the pathogenetic process and infiltration characteristics of acute leukemia and malignant lymphoma. This can provide a new method to cure the above-mentioned hematologic tumors.

Adolescent↗

Chronic lymphocytic leukemia with CNS involvement.

Direct involvement of the brain by chronic lymphocytic leukemia (CLL) is extremely rare. This is the second documented case. A 63 year-old-man presented with motor deficits. Conventional radiographic imaging showed no abnormalities but an MRI scan of the head showed a high signal intensity lesion in the left cerebellum. Biopsy of this area showed a perivascular infiltrate of small B lymphocytes consistent with CLL involvement. The patient was treated with radiotherapy and had some improvement in symptoms. Three years later he remains alive with some neurologic deficit. This case confirms that CLL can be complicated by direct brain involvement.

Brain↗

Pulmonary infiltrates in patients with haematologic malignancies: transbronchial lung biopsy increases the diagnostic yield with respect to neoplastic infiltrates and toxic pneumonitis.

We retrospectively evaluated 107 fiberoptic bronchoscopies with and without transbronchial lung biopsy (TBLB) in 98 consecutive patients with haematologic malignancies and pulmonary infiltrates. Bronchoalveolar lavage (BAL) was performed in 45 and BAL plus TBLB in 62 procedures. There was no procedure-related severe haemorrhage, pneumothorax or death. Infectious aetiology was identified in 26 of 107 (24%), toxic pneumonitis in 17 of 107 (16%) and neoplastic infiltration in 9 of 107 (8.5%) episodes. Combined BAL and TBLB was significantly superior to BAL alone with respect to the diagnosis of neoplastic infiltrates (p=0.008) and toxic pneumonitis (p<0.001) and should therefore be included in the diagnostic work-up of this patient cohort.

Adult↗

[Pseudo-acute surgical abdomen and acute leukemia].

The so-called pseudo-acute abdomen has been reported in acute leukemia, both at diagnosis or relapse. The clinical presentation may be misleading and life-threatening, due to the possible infiltration of any abdominal viscera. The authors present a series of eight patients and emphasize the management specificities of such patients and the possibility of long-term remissions, regardless of the severity of the initial presentation.

Abdomen, Acute↗