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PubMed1992

[The importance of bone marrow examination for hemoblastoses].

Morphological bone marrow evaluation is an integral component in staging patients with hematological malignancies. In acute leukemias or myelodysplastic syndromes cytologic examination is crucial since it allows precise analysis on the individual cell level. Histological examination of an iliac crest trephine biopsy is mandatory in malignant lymphomas because of the frequent nodular involvement of bone marrow in these diseases. In recent years magnetic resonance tomography (MRT) has been shown to be a sensitive method for detecting marrow infiltration in a variety of marrow diseases. In malignancies with focal marrow involvement, such as malignant lymphoma, MRT is today a useful complement to morphological bone marrow evaluation.

Acute Disease↗
PubMed1996

Leukaemia cutis in chronic CD8+ T lymphocytic leukaemia.

A 66-year-old woman with CD8+ chronic lymphocytic leukaemia developed multiple indurated erythema or plaques. A skin biopsy specimen showed dense infiltration of leukaemia cells in the dermis and subcutaneous tissue. Most of the infiltrating cells were CD8 + cells. To our best knowledge, leukaemia cutis such as this case showing plaques with diffuse infiltration of CD8 + cells has not been reported previously.

Aged↗
PubMed2004

Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome.

We evaluated the frequency and prognostic significance of extramedullary infiltrates (EMI) at presentation of acute myeloid leukemia (AML) in adult patients. Of 331 cases with de novo AML, 101(30.5%) had extramedullary infiltrates at diagnosis. The extramedullary manifestations included: lymphadenopathy, splenomegaly, hepatomegaly, gingival hypertrophy, skin infiltrates and involvement of central nervous system (CNS). Patients with EMI had a high initial WBC count and a high proportion of M4/M5 morphological variants. The complete remission rate (CR) with induction chemotherapy was lower in patients with EMI (P=0.0077) and their overall survival was also inferior (P=0.0017). Flow cytometric evaluation of the surface antigens expressed by the leukemic blasts for CD34, TdT, HLADR, CD7, CD19 and CD56 found that only CD56 expression was associated with EMI. The association of CD56 expression with lymphadenopathy was statistically significant (P=0.035). Abnormal karyotypes were found in 50.6% of patients with EMI and 49.7% of patients without EMI. Only 11q23 abnormalities were associated with specific sites of EMI; lymphadenopathy (P=0.0111) and gingival hypertrophy (P=0.0016). Our study of adult AML patients demonstrates that EMI at diagnosis is associated with CD56 expression by leukemic blasts, 11q23 karyotypic abnormalities, low complete remission rate and poor overall survival.

Acute Disease↗
PubMed2004

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases.

OBJECTIVE: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B- and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor-ligand pair in thyroid autoimmunity. METHODS: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. RESULTS: We found no differences between the percentages of peripheral blood CXCR5+ T- and B-cells in GD patients (n=10) and healthy controls (n=10). In GD patients, the number of memory CD4+ cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroid-derived (18+/-3%) compared with peripheral blood T-lymphocytes (8+/-2%). The highest CXCL13 mRNA levels were found in HT (n=2, 86.1+/-1.2 zmol (10(-21) mol) cDNA/PCR) followed by GD tissues (n=16, 9.6+/-3.5). Only low amounts were determined in thyroid autonomy (TA) (n=11) thyroid tissues, irrespective of whether the autonomous nodule (0.5+/-0.1) or the surrounding normal tissue (1.8+/-0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1+/-6.8; GD: 17.4+/-10.6; TA(nodule): 0.8+/-0.5; TA(normal): 4.4+/-3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. CONCLUSIONS: CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity.

Adult↗
PubMed1989

[CD33-positive acute lymphoblastic leukemia with breast tumor and cavernous sinus tumor].

A 38-year-old woman was diagnosed as acute lymphoblastic leukemia (L2) in Oct. 1985. After VP and AdVEMP therapy, complete remission was obtained. In Oct. 1987, she noticed bilateral breast tumors and leukemic cell infiltrations were shown in a biopsy specimen of the breast tumor. Bone marrow was occupied with 94 percent blasts. The second complete remission was achieved by the AdVP therapy. In Nov. 1988, she developed double vision and photophobia. The examinations of CT and MRI showed cavernous sinus tumor, and 20 percent blasts were recognized in a bone marrow aspirate. The leukemic cells were negative for peroxidase, but were positive for both lymphoid and myeloid cell surface markers (CD2, CD5, CD7, CD33). The two color flowcytometry showed that CD5 and CD33 were simultaneously expressed on the leukemic cells.

Adult↗
PubMed1987

Distribution of immunoglobulin containing cells in human bone marrow of patients with leukemia.

In the bone marrow of leukemic patients (31 cases), the number of immunoglobulin containing cells per unit square significantly decreased to the level of approximately 20-50% of the age-matched control, although the serum level of immunoglobulin in these patients was almost comparable to the control level. The number of immunoglobulin containing cells in the bone marrow was inversely related with the degree of infiltration of leukemic cells and the correlation of Ig-G containing cell count (Y) and percentage of blast cells (X) was Y = 91.8-1.9X (r = -0.436, P less than 0.05). Follow-up examination of the bone marrow after chemotherapy revealed that the recovery of the number of immunoglobulin containing cells in the remission state appeared to occur in younger patients, but not in older ones.

Adolescent↗
PubMed1994

Immunohistochemical evaluation of myeloid leukemia infiltrates (granulocytic sarcomas) in formaldehyde-fixed, paraffin-embedded tissue.

Paraffin sections of granulocytic sarcomas (GS) (n = 30) were immunohistochemically evaluated for CD3, CD15 (LeuM1), CD20 (L26), CD31, CD34, CD43, CD45, CD68 (KP1), lysozyme, myeloperoxidase (BM1), CD45RO (UCHL1), and LN5 with an avidin-biotin amplification system and a peroxidase-based color development system with DAB as a chromogen. CD45 positivity was present in all lymphomas and 24 of 25 granulocytic sarcomas. Lysozyme and CD43 labeled 26 of 29 granulocytic sarcomas, showing intense cytoplasmic staining. LN5 (membrane-staining) and CD68 (subtle cytoplasmic caplike staining) were found in 20 of 30 cases, often only focally. BM1 and CD15 mainly labeled maturing granulocytes and mostly were negative in primitive myeloid cells. Myeloid progenitor cell antigens CD31 and CD34 were seen in 7 and 12 of 30 cases, respectively. They seemed to recognize different subsets of myeloid leukemia infiltrates (16 cases positive for at least one); the use of CD31 and CD34 for defining these subsets should be evaluated further. Features suggesting a dual phenotype--T-cell and myeloid (positive for CD3, CD68, and lysozyme)--were documented in two cases. In contrast, lymphoblastic lymphomas (n = 4) were positive for CD3 and CD43 but negative for CD68, lysozyme, CD31, CD34, LN5, and myeloperoxidase. Lymphocytic lymphomas (n = 10) were positive for CD20 and CD43 but negative for all other markers. Small, round-cell tumors (n = 15) were negative for all markers. If T-cell and B-cell differentiation can be excluded with other markers, CD43+ is a sensitive marker for myeloid differentiation. Our results show that several markers are useful in the identification of myeloid leukemia infiltrates and in distinguishing them from lymphoblastic and lymphocytic lymphomas and small round-cell tumors in formaldehyde-fixed, paraffin-embedded tissue.

Adult↗
PubMed1993

Milky spots as the implantation site for malignant cells in peritoneal dissemination in mice.

We examined the site-specific implantation of cancer cells in peritoneal tissues after an i.p. inoculation of 10(5) P388 leukemia cells. Twenty-four h after the inoculation, the number of viable cancer cells infiltrating into specific tissue sites of the peritoneum was estimated by an i.p. transfer method. A descending order of tissue implantation with cancer cells was established as omentum > gonadal fat > mesenterium > posterior abdominal wall > stomach, liver, intestine, anterior abdominal wall, and lung. A significant correlation was established between the logarithm of the number of infiltrating cancer cells and the logarithm of the number of milky spots. Next, the omentum was examined microscopically after i.p. inoculation with P388 leukemia cells labeled with bromodeoxyuridine or B-16 PC melanoma, which were differentiated from the other cells by an immunocytological method using anti-bromodeoxyuridine antibody or by the melanin of the B-16 PC melanoma cells. These cancer cells were found microscopically to be infiltrating only the milky spots, whereas none were seen at the other sites. These results suggest that cancer cells seeded i.p. specifically infiltrate the milky spots in the early stage of peritoneal metastases.

Animals↗
PubMed2000

Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis.

BACKGROUND: A 10-year-old boy with a history of acute lymphoblastic leukaemia (ALL), but without previous evidence of central nervous system involvement, presented with seizures 3 years after complete remission. MATERIALS AND METHODS: MRI showed bilateral enlargement of the optic nerves despite normal ophthalmological examination. RESULTS: Only the third cerebrospinal fluid examination showed 2 % blasts without concomitant bone-marrow infiltration. Enlargement of the optic nerves was consistent with bilateral leukaemic peri-optic nerve infiltration. The appearances returned to normal after chemotherapy. CONCLUSION: The optic nerves are a potential site of relapse in patients with systemic and meningeal ALL, even in the absence of ophthalmological signs.

Child↗
PubMed2004

The value of white blood cell count in patients with swollen discs.

BACKGROUND: A broad differential diagnosis has to be considered in a patient with swollen discs. Myeloproliferative disorders such as leukemia and lymphoma can in rare cases cause infiltrative optic neuropathy. HISTORY AND SIGNS: Two patients initially presented with slowly progressive severe visual loss. History was unremarkable except for previously noted slightly elevated white blood cell count for which - according to their general physicians - no treatment or work-up was required. At presentation, bilateral disc swelling was present. Magnetic resonance imaging showed enhancement of the entire optic nerves sparing the chiasm. No other intracranial lesion was found. Cerebrospinal fluid contained no malignant cells. THERAPY AND OUTCOME: After bone marrow aspiration the diagnosis of non-Hodgkin's lymphoma and granulocytic leukemia, respectively, was made. Treatment resulted in visual recovery. CONCLUSION: Work-up in a patient with swollen discs should always include white blood cell count. If the result is abnormal further exploration should be pursued. Elevated white blood cell count may be the only hint of optic nerve infiltration caused by a myeloproliferative disorder and its treatment can result in remarkable recovery.

Aged↗
PubMed2005

[Successful rituximab treatment in a patient with refractory hairy cell leukemia-Japanese variant and suffering from acute respiratory distress].

A 69-year-old man was referred to our hospital because of thrombocytopenia and was diagnosed as having hairy cell leukemia-Japanese variant (HCL-Jv) in December 2000. In June 2002, he was treated with pentostatin for progression of thrombocytopenia, but his response was incomplete. In addition, the number of hairy cells (HCs) in his peripheral blood (PB) began gradually to increase. He received treatment with interferon-alpha and cladribine, but he failed to respond completely to these treatments. The HCs in his PB decreased after splenic irradiation in July, 2004. However, he was admitted with acute respiratory distress in November. His white blood cell count was 123.1 X 10(9)/L with 91% HCs. Radiography and computed tomography of his chest revealed ground-glass opacity in both lungs. A bone marrow (BM) aspirate indicated increased cellularity with an 84% HC infiltration level. Based on these findings, we diagnosed pulmonary infiltration by HCs. Rituximab was administered weekly at a dose of 375 mg/m2, and he also received low-dose melphalan in a supportive role. After 8 courses of rituximab therapy, the HCs disappeared in his PB and BM, and his pulmonary infiltrates subsided. These results suggest that rituximab may be a very effective treatment for refractory HCL-Jv.

Aged↗
PubMed1994

Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T-cell leukemia.

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T-cell leukemia (ATL) and other malignant and non-malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 +/- 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 +/- 9.2 U/ml). Non-ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 +/- 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 +/- 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL.

CD4 Antigens↗
PubMed2006

Acute renal failure caused by renal infiltration by hematolymphoid malignancy.

Renal involvement by a malignant infiltrative process is often suspected in patients with bilaterally enlarged kidneys and concurrent malignancies. Acute renal failure (ARF) can rarely occur secondary to such an infiltrative process. We present 2 cases in which ARF is attributable to malignant hematolymphoid infiltration. The first case involves diffuse, bilateral involvement of the kidneys by non-Hodgkin's lymphoma. The patient's renal function improved dramatically after the initiation of chemotherapy, clearly linking the development of ARF to the malignant process. In the second case, infiltration of the kidneys by plasma cell leukemia resulted in dialysis dependence. To our knowledge, this represents the first reported case of ARF attributable to documented renal infiltration by plasma cell leukemia. A review of the potential causes of renal failure in hematolymphoid malignancy, focusing on the direct impact of the infiltrative process and on the spectrum of renal disease in plasma cell dyscrasia, is presented.

Acute Kidney Injury↗
PubMed1996

Leukemia cutis: Darier's sign in a neonate with acute lymphoblastic leukemia.

Infantile leukemia accounts for only 3% of childhood leukemia. Leukemia cutis occurs in 25% to 30% of infants with congenital leukemia and is more frequently associated with acute myeloid leukemia than with acute lymphoblastic leukemia. We describe an infant in whom hyperpigmented macules that developed when the patient was 2 weeks old demonstrated Darier's sign when he was 4 weeks old. Acute lymphoblastic leukemia, early pre-B-cell type, was diagnosed when the patient was 10 weeks old. Examination at that age revealed 1 to 2 cm, firm, mildly tender nodules clustered on the scalp, face, and extremities, less severe involvement of the trunk, and marked induration of the face and eyelids. Darier's sign was elicited from the less infiltrated truncal lesions. Histologic examination revealed a dense monomorphous infiltrate consisting of pleomorphic, undifferentiated cells. No mast cells were revealed by Giemsa staining. This case is to our knowledge the first reported example of leukemia cutis demonstrating Darier's sign.

Humans↗