Diagnosis of granulocytic sarcoma facilitated by monoclonal antibodies

A 36 year old woman presented with a nasopharyngeal tumour which was diagnosed and treated as diffuse large cell lymphoma. Twelve mth later the patient developed acute myeloid leukemia. At this stage, the original biopsies were reviewed and considered in retrospect to be granulocytic sarcoma on the basis of staining for chloracetate esterase and lysozyme. She achieved and maintained marrow and peripheral blood remission with chemotherapy, but developed several cutaneous nodules and 2 breast lumps. One breast lump was excised and was found, by the use of monoclonal antibodies, to carry myeloid markers. Thus monoclonal antibodies provided additional confirmatory evidence for the diagnosis of granulocytic sarcoma.     

Granulocytic Sarcoma in MLL-Positive Infant Acute Myelogenous Leukemia : Fluorescence in Situ Hybridization Study of Childhood Acute Myelogenous Leukemia for Detecting MLL Rearrangement

Granulocytic sarcoma is considered to be rare and its frequent occurrence is associated with specific genetic changes such as t(8;21). To investigate an association between MLL (mixed lineage leukemia or myeloid-lymphoid leukemia) rearrangement and granulocytic sarcoma, we applied fluorescence in situ hybridization for detection of the 11q23/MLL rearrangements on the bone marrow cells of 40 patients with childhood acute myelogenous leukemia (AML). Nine (22.5%) of 40 patients exhibited MLL rearrangements. Three (33.3%) of these nine patients had granulocytic sarcoma and were younger than 12 months of age. Of these three patients one presented as granulocytic sarcoma of both testes with cerebrospinal fluid involvement, the second case presented in the form of an abdominal mass, and the third as a periorbital granulocytic sarcoma. On the other hand, no granulocytic sarcomas were found among MLL-negative patients. It is likely that MLL-positive infant AML may predispose granulocytic sarcoma. Regarding the findings of our study and those of other reports, we would guess that the incidence of granulocytic sarcoma in pediatric MLL-positive AML may be equal to or greater than the 18 to 24% described in AML with t(8;21). Further investigations designed to identify 11q23/MLL abnormalities of leukemic cells or extramedullary tumor may be helpful for the precise diagnosis of granulocytic sarcoma.     

Cytogenetic divergence of the same blastic clone in transformed chronic granulocytic leukemia: no effect on morphologic and immunologic features.

A 19-year-old man with Ph-positive chronic granulocytic leukemia developed lymphoblastic transformation. Cytogenetic evolution was observed, with an abnormal clone showing i(17q) together with the t(9;22). Chronic phase of the chronic granulocytic leukemia were re-established with systemic chemotherapy, which also led to disappearance of the clone with i(17q). However, the acute lymphoblastic leukemia relapsed after 6 weeks, with the emergence of a phenotypically and genetically identical but cytogenetically distinctive clone. Our findings suggest that cytogenetic evolution in transformed chronic granulocytic leukemia reflects only the instability of the blastic clones, and may not determine its phenotypic differentiation.     

Detection of terminal transferase in paraffin sections with the immunoperoxidase technique.

Terminal deoxynucleotidyl transferase (TdT) is an early T-cell differentiation marker in a number of species, including man. We have demonstrated TdT in the nuclei of cortical thymocytes in paraffin-embedded sections of calf, rat, and human thymus by indirect immunoperoxidase techniques. In addition, these techniques have been used to verify and extend enzyme assay results by detecting TdT in blast cells from 10 patients with convoluted T-cell lymphoma/leukemia, 1 patient with acute granulocytic leukemia, 1 patient with chronic granulocytic leukemia in blast crisis, and 1 patient with non-T non-B acute lymphocytic leukemia.     

A hybrid eosinophilic-basophilic granulocyte in chronic granulocytic leukemia

Morphologic observation of the peripheral blood smear from a patient with chronic granulocytic leukemia suggested the presence of eosinophilic and basophilic granules in the same individual granulocyte. To unambiguously identify eosinophilic and basophilic granules simultaneously in the same preparation, the authors developed a cytochemical staining procedure using basophil-specific toluidine blue and eosinophil-specific cyanide-resistant peroxidase. Using this new dual stain, they demonstrated that ten out of ten chronic granulocytic leukemia patients they examined had cells that contained both eosinophilic and basophilic granules. The identity of the granules was corroborated by electron microscopic studies. These observations suggest that lineage confusion is common in chronic granulocytic leukemia.     

小儿急性白血病患者外周血T淋巴细胞亚群的研究

本文用单克隆抗体SACI-Ig花环法测定了小儿急性白血病及再生障碍性贫血患者外周血T淋巴细胞亚群的变化。结果显示,在急性淋巴细胞性白血病及再生障碍性贫血患儿OKT8~ 细胞均明显高于正常,OKT4~ /OKT8~ 比值显著降低,但在急性粒细胞性白血病患儿淋巴细胞亚群变化不明显。这提示,抑制性T细胞(OKT8~ )的增多可能与小儿急性淋巴细胞性白血病及再生障碍性贫血的发生或发展有关。     

Double 9;22 translocation with hyperdiploidy appearing in blastic transformation of chronic granulocytic leukemia

Chromosome studies in a 26-year-old female with Ph¹-positive chronic granulocytic leukemia showed the development of both hyperdiploid and tetraploid cell lines in the blastic transformation phase. An additional 9;22 translocation and additional chromosomes No. 8, 11, 13, and 22 were found in the hyperdiploid cell line. This unusual finding suggests that the hyperdiploidy may have developed from misdivisions in the tetraploid cell line rather than by the more accepted mechanism of nondisjunction or selective endoreduplication from a diploid cell.     

Granulocytic sarcoma in the absence of acute myeloid leukemia: a case report

Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic precursor cells. The most common sites of presentation are bone, periosteum, soft tissue, lymph node, skin, and infrequently small intestine. The tumor may develop during the course of acute myeloid leukemia, chronic myeloid leukemia or other myelodysplastic disorders. It can occur without blood or bone marrow manifestations of leukemia and in this case, the diagnosis is difficult. Our patient was initially diagnosed as a case of T-cell non Hodgkin's lymphoma and received one cycle of CHOP with only transient improvement in his symptoms. Subsequently, his biopsy slides were reviewed at our centre and were reported as granulocytic sarcoma.     

Translocation t (8;21) associated with marked granulocytic hyperplasia

A 16-year-old boy with leukemia had a marked leucocytosis (165 x 10(9)/L) at presentation. The large number of neutrophils, myelocytes, and metamyelocytes and negative leucocyte alkaline phosphatase reaction raised the possibility of chronic myeloid leukemia. Cytogenetic analysis showed a deletion of chromosome 7, a t (8;21), a missing Y chromosome, and, in some cells, duplication of the der(21). The Philadelphia chromosome was not detected, nor was the breakpoint cluster region of chromosome 22 found to be rearranged. Myeloid leukemia with t (8;21) can therefore be associated with a greater degree of granulocytic hyperplasia than has so far been apparent, and cytogenetic analysis in this case has been crucial in distinguishing leukemia types.     

Multiple myeloma terminating in acute eosinophilic leukemia

A 71-year-old woman with multiple myeloma was successfully managed for 8 years with melphalan (total dose 2056 mg). She developed a refractory anemia (myelodysplastic state), which terminated in acute eosinophilic leukemia. This form of acute leukemia, induced by chemotherapy, appears to be very rare. The cytogenetic changes, including 5q- and monosomy 7, were similar to those observed in other patients with acute nonlymphocytic leukemia as a secondary malignancy following treatments of other primary tumors.     

Undifferentiated leukemia following treatment of gastric cancer with 5 fluorouracil, doxorubicin, mitomycin C chemotherapy

Secondary leukemias are an increasingly well recognized complication of cancer chemotherapy. We report on the development of undifferentiated leukemia in a forty one year lady, eighteen months after treatment of gastric cancer with 5-fluorouracil (5 FU), doxorubicin and mitomycin C. She developed progressive weakness and pancytopenia over a period of few months. Leukemic blasts which were undifferentiated by immunophenotyping were seen in her peripheral blood. She died of intracranial haemorrhage during induction chemotherapy for the leukemia. Undifferentiated leukemia is a rare complication of FAM chemotherapy for gastric cancer.     

Acute leukemia associated with trisomy 8 mosaicism and a familial translocation 46,XY,t(7;20)(p13;p12).

A patient is shown to have acute granulocytic leukemia, bone marrow mosaicism, and cutaneous fibroblast mosaicism for trisomy 8, an inherited reciprocal translocation involving the short arms of chromosomes 7 and 20, and a family history of cancer. A normal sister who had the same balanced chromosome translocation was evaluated for a preleukemic state; the results were unremarkable. The inherited translocation and postzygotically derived trisomy 8 are thought to represent additive factors contributing to the development of leukemia in the patient.     

Acute leukemia associated with trisomy 8 mosaicism and a familial translocation 46,XY,t(7;20)(p13;p12)

A patien is shown to have acute granulocytic leukemia, bone marrow mosaicism, and cutaneous fibroblast mosaicism for trisomy 8, an inherited reciprocal translocation involving the short arms of chromosomes 7 and 20, and a family history of cancer. A normal sister who had the same balanced chromosome translocation was evaluated for a preleukemic state; the results were unremarkable. The inherited translocation and postzygotically derived trisomy 8 are thought to represent additive factors contributing to the development of leukemia in the patient.     

Lobular carcinoma with cytoplasmic granules

We report on a case of invasive lobular carcinoma of the breast with a previously undescribed cytologic feature. Diff-Quik-stained cytologic preparations showed uniform single cells with prominent coarse cytoplasmic granules. Ultrastructurally, the granules showed features suggestive of autophagosomes and/or degenerative mitochondria. The cytologic differential diagnosis included granulocytic sarcoma, metastatic melanoma, extramedullary hematopoiesis, large granulocytic leukemia/lymphoma, and mast-cell tumor. Adjunctive studies were helpful in the diagnosis of carcinoma. Histologic study of the mastectomy specimen showed classic type of invasive lobular carcinoma.     

Effect of repeated bloodletting on the incidence of 2,7-FAA-induced rat leukemia.

The oral administration of N,N'-2,7-fuorenylenebisacetamide (2,7-FAA) induced leukemia, especially mature granulocytic leukemia, in rats. 2,7-FAA was administered to the rats of the Wistar strain and a small amount of bloodletting was repeated for a long period. The incidence of leukemia and mature granulocytic leukemia became elevated by bloodletting. The induction of mature granulocytic leukemia might be increased by the promotion of granulopoiesis which had been suppressed by 2,7-FAA.     

Pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis in a patient with busulfan lung

A 32-year-old Japanese man with chronic granulocytic leukemia died of respiratory failure. Autopsy revealed alveolar proteinosis and pulmonary fibrosis, complicated by disseminated atypical mycobacteriosis. Epithelial hyperplasia caused by busulfan therapy was probably responsible for the induction of excessive surfactant production, resulting in alveolar proteinosis, and the immunosuppressive state due to chronic granulocytic leukemia was probably related to the induction of disseminated atypical mycobacteriosis.     

EFFECT OF REPEATED BLOODLETTING ON THE INCIDENCE OF 2,7-FAA-INDUCED RAT LEUKEMIA

The oral administration of N,N'-2,7-fuorenylenebisacetamlde (2,7-FAA) induced leukemia, especially mature granulocytic leukemia, in rats. 2,7-FAA was administered to the rats of the Wlstar strain and a small amount of bloodletting was repeated for a long period. The incidence of leukemia and mature granulocytic leukemia became elevated by bloodletting. The induction of mature granulocytic leukemia might be increased by the promotion of granulopoiesis which had been supressed by 2,7-FAA.     

Isolated biliary granulocytic sarcoma followed by acute myelogeneous leukemia with multilineage dysplasia: a case report and literature review

Granulocytic sarcoma is a rare extramedullary tumor composed of myeloid progenitor cells. Primary involvement of the biliary tract without evidence of leukemia is exceedingly rare. Here, we report an isolated biliary granulocytic sarcoma in a 30-yr-old man who presented with jaundice, fever, and chill without any evidence of leukemia. However, five months after the diagnosis, he developed acute myelogenous leukemia with multilineage dysplasia and chromosomal abnormality. A rare possibility of biliary granulocytic sarcoma should be considered as a differential diagnosis in patients with obstructive jaundice. A histologic evaluation by aggressive diagnostic intervention is important and may improve prognosis.     

Site of origin of 2,7-FAA-induced rat leukemia.

Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-FAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and comspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.     

SITE OF ORIGIN OF 2,7-FAA-INDUCED RAT LEUKEMIA

Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-PAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and conspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.