Rhabdomyosarcoma with bone marrow metastasis simulating acute leukemia. Report of two cases

Rhabdomyosarcoma manifested as a systemic disease is very rare and cases showing diffuse metastasis in the bone marrow are most unusual. Recently we encountered two cases of rhabdomyosarcoma with diffuse bone marrow metastasis which were clinically manifested as acute leukemia. The first patient was a 15-year-old female, who was admitted in 1982 with pancytopenia and many large primitive cells in bone marrow aspirates, hematological malignancy being diagnosed. Thereafter the bilateral breasts showed rapid swelling and a biopsy specimen revealed the histological features of typical alveolar rhabdomyosarcoma. The primary site of the neoplasm remained undetermined during the course. At autopsy, it was disclosed that the neoplasm originated from the left thigh and showed generalized metastasis. The second patient was a 38-year-old man, who was admitted in 1986 because of a nasal polyp obstructing the nasal cavity, and persistent nasal bleeding. Peripheral blood samples showed leukoerythroblastosis and thrombocytopenia, and large primitive cells were found in bone marrow aspirates, so that hematological malignancy was initially diagnosed. A biopsy specimen of the nasal polyp showed proliferation of large round cells and electron microscopy demonstrated the ultrastructural features of rhabdomyosarcoma.     

Diffuse large B-cell lymphoma initially manifesting in bone marrow. A case report

We presented the case of diffuse large B-cell lymphoma initially manifesting in bone marrow without lymph nodes' swelling and other extranodal lesion. A 68-year-old woman was suffering from general fatigue and fever. Because atypical cells were identified in the peripheral blood, a bone marrow puncture and random skin biopsy were performed. In myelogram, it was suspicious for myelodysplastic disease because lymphoma cells resembled other atypical hematopoietic cell. In biopsy specimen of bone marrow, atypical cells diffusely infiltrated, which could be called "paced bone marrow". On the other hand no atypical cell identified in the vessels of dermis and subcutaneous tissue by random skin biopsy. Immunohistochemically, atypical cells in bone marrow were diffusely positive for B-cell marker (CD20). These results lead this case to be diagnosed as diffuse large B-cell lymphoma initially manifesting in the bone marrow. In this case, it was very useful that bone marrow biopsy and myelogram were evaluated simultaneously. Quick and accurate diagnosis is possible by combining immunohistochemical analysis using both myelogram and biopsy specimen.     

Bone marrow involvement at presentation in pediatric non-haematological small round cell tumours

Pediatric small round cell tumors (SRCT) are a group of neoplasms occurring in children, which have in common a cytomorphology of groups of small round cells with scanty cytoplasm. The common SRCT encountered are neuroblastoma, retinoblastoma, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), rhabdomyosarcoma and lymphoma which show varying degrees of bone marrow involvement and bone marrow evaluation forms a part of the initial staging procedure. This study was undertaken to evaluate marrow involvement at presentation in pediatric non hematological SRCT. 7833 bone marrow aspirates done over a period of three years in different malignancies were analysed and of these 180 aspirates were performed in patients of pediatric non hematological SRCT at presentation. These cases were evaluated in detail for incidence of marrow involvement. Thirty two (17.7%) cases showed marrow involvement and these cases have been analysed with respect to the primary tumor. The SRCT showing involvement of bone marrow included neuroblastoma (48.8%), retinoblastoma (11.1%), Ewing's sarcoma/PNET (8.6%) and rhabdomyosarcoma (3.2%).These findings are discussed in the light of available world literature.     

Alveolar rhabdomyosarcoma infiltrating bone marrow at presentation: the value to diagnosis of bone marrow trephine biopsy specimens.

AIMS: To describe the histological appearances of bone marrow infiltrated with rhabdomyosarcoma at presentation and to determine their value in establishing the diagnosis. METHODS: Patients presenting over seven years in the northern health region of England with rhabdomyosarcoma were studied. Bone marrow aspirates and trephine biopsy specimens taken at presentation were examined. RESULTS: Seven of 32 patients with rhabdomyosarcoma had bone marrow infiltration, resulting in marrow failure in all cases, at diagnosis. The diagnosis was established in these seven by the typical cytological appearances and immunophenotype of the infiltrating cells (all seven patients) and cytogenetic abnormalities (three patients). Histological examination of the bone marrow showed a pseudoalveolar pattern with fibrous septal bands, enlarged vascular channels, and lack of cohesion of the tumour cells within the subdivided aggregates in all seven. In four cases multinucleate giant cells, often with peripherally sited nuclei, were found. CONCLUSIONS: These histological features of infiltrated marrow are so characteristic that the diagnosis of alveolar rhabdomyosarcoma can be made, or at least suspected, in many cases even without recourse to technically difficult and expensive further investigations. Bone marrow biopsy should be a routine part of the investigation of patients with bone marrow failure and will be of particular value in the diagnosis of those with disseminated alveolar rhabdomyosarcoma.     

Systemic rhabdomyosarcoma with diffuse bone marrow involvement. Case report of an unusual presentation

Rhabdomyosarcoma presenting as a systemic disease is rare. This report concerns a 12-year-old girl who came to medical attention for what was thought to be a hematologic malignancy. Diffuse lytic bone lesions and large primitive cells in the bone marrow exhibiting erythrophagocytosis supported this diagnosis. During the course of the disease, a soft tissue mass in the region of the left ankle was removed and was a typical alveolar rhabdomyosarcoma. Retrospective review of the marrow, including electron microscopy, demonstrated that the primitive marrow cells were probably rhabdomyoblasts as well. The clinical course was a rapid downhill one in which lytic bone lesions and hypercalcemia were prominent. Although rhabdomyosarcoma eventually may disseminate, initial widespread disease without a clinically apparent primary can be a diagnostic dilemma. This clinical presentation, in combination with the recognized aggressiveness of the alveolar histologic subtype, identifies a rare subgroup of patients with rapidly fatal disease.     

Comparison of the diagnostic value of bone marrow biopsy and bone marrow aspiration in neoplastic disease

The Jamshidi-Swaim biopsy needle was utilized to perform 205 bone marrow biopsies, accompanied by simultaneous bone marrow aspirates, on patients with lymphoma, leukaemia, and a variety of solid tumours. There was no significant morbidity. There were 67 positive findings with biopsy and 42 with aspiration. The two techniques were complementary in Hodgkin's disease, non-Hodgkin's lymphoma, breast carcinoma, bronchogenic carcinoma, malignant melanoma, and in leukaemia. We have examined the bone marrow biopsies and aspirates with respect to the adequacy of the bone marrow biopsy specimen, the number of positive biopsies in the various categories of neoplasia, and the disparity of biopsy and aspirate, finding that 28 of the 67 positive biopsies (41.8%) had negative aspirates. These data and specimens obtained compared quite favourably with other series in which a modification of the Vim-Silverman needle was used.     

Bone marrow involvement by metastatic solid tumors

A five year experience with bone marrow aspirates and biopsies positive for metastatic carcinoma is reviewed. Marrow examination in 25 cases detected metastasis. The common primary tumors with marrow metastasis were neuroblastoma, carcinoma breast and prostate. In 56% cases primary site could not be ascertained from bone marrow as metastatic tumor showed undifferentiated morphology. The study demonstrates the usefulness of combining trephine biopsy with aspirate examination for increased detection of bone marrow metastasis.     

Primitive rhabdomyosarcoma presenting with diffuse bone marrow involvement: an immunohistochemical and ultrastructural study

We recently identified three cases of primitive rhabdomyosarcoma (PRMS) presenting with diffuse bone marrow infiltration but inconspicuous soft tissue primaries, referred to The Johns Hopkins Hospital (JHH) as acute leukemia. In each case, the diagnosis of rhabdomyosarcoma was established using immunohistochemical staining and electron microscopy. Ultrastructural examination of tumor cells showed a feltwork of thin filaments, discontinuous basal lamina, glycogen, and primitive cell junctions without cell processes or neurosecretory granules. This presentation of PRMS may be more common than recognized, since it can be readily misdiagnosed as a hematopoietic tumor. While positive staining for muscle-specific actin, desmin, myoglobin, or other markers of skeletal muscle differentiation may be diagnostic, negative staining is inconclusive, requiring recognition of the "minimal" ultrastructural findings of primitive rhabdomyosarcomas.     

小儿血液病骨髓针刺活检临床病理学分析

目的：探讨小儿骨髓活检特点及其病理诊断意义。方法：对比分析３６１例有血液病临床表现的患儿骨髓针刺抽吸涂片和活组织检查结果。结果：比较两种检查方法，在判断增生程度时存在显著差别。活检可以提高再生障碍性贫血、血小板减少性紫癜、骨髓异常增生综合征和转移性恶性肿瘤的诊断率。结论：骨髓活检对造血系疾病诊断可提供有力证据。     

Abdominal Burkitt's lymphoma diagnosed by fine needle aspiration cytology--a case report

A case of abdominal Burkitt's lymphoma diagnosed through aspiration cytology is described. This 9-year-old boy presented with abdominal pain and distention for three months accompanied by fever and night sweat during the last month. An abdominal sonography and CT scan showed hepatosplenomegaly and an intrahepatic mass with celiac lymph node enlargement, ascites, and pleural fluid. A peripheral blood smear showed a few blast cells. Aspiration of the abdominal mass revealed very cellular aspirates consisting of diffusely scattered small monotonous round cells. The cells had little cytoplasm, along with round nuclei that showed clear-cut nuclear membrane, coarse chromatin pattern, and multiple small prominent nucleoli. Differential diagnoses considered were small round cell sarcomas such as malignant lymphoma, neuroblastoma, Ewing's sarcoma, and rhabdomyosarcoma. Of these, malignant lymphoma of the small noncleaved cell type was most consistent with the results of several studies including immunohistochemical staining, peripheral blood smear, and bone marrow biopsy. The cells were positive for leukocyte common antigen (LCA) and showed finely vacuolated basophilic cytoplasm in both the peripheral blood smear and bone marrow biopsy, characteristic of Burkitt's lymphoma cells.     

Osteosarcoma with rhabdomyosarcomatous component or so-called malignant mesenchymoma of bone

BACKGROUND: Primary malignant mesenchymoma of the bone is a rare neoplasm consisting of two or more unrelated malignant mesenchymal components. The literature reports fewer than 20 cases, most of which were composed of osteosarcoma and liposarcoma. OBSERVATION: We report an exceedingly rare case of primary malignant mesenchymoma of bone composed of rhabdomyosarcoma, osteosarcoma, and a minor chondrosarcoma component, arising in the right proximal humerus of a 15-year-old girl. The rhabdomyosarcomatous component was present in the initial biopsy and persisted in surgical specimen following chemotherapy. CONCLUSION: Effect of chemotherapy is enigmatic since rhabdomyosarcomatous component could appear, persist or disappear after chemotherapy according to literature.     

Hairy cell leukemia variant with features of intrasinusoidal bone marrow involvement

Hairy cell leukemia variant (HCL-V) is a rare lymphoproliferative disorder. We report a case of HCL-V with an intrasinusoidal pattern of bone marrow involvement without interstitial or diffuse infiltration that is typical of HCL and its variant. The peripheral blood and bone marrow aspirates demonstrated abnormal lymphoid cells with cytoplasmic projections that were weakly positive for tartrate-resistant acid phosphatase cytochemical staining. Immunostaining of the bone marrow biopsy specimen showed that these cells were strongly positive for CD20, located within bone marrow sinusoids, and weakly positive for DBA44. By flow cytometry, these cells were positive for CD19, CD20, CD11c, and CD103, exhibited lambda light chain restriction, and were negative for CD25. The patient was initially diagnosed as having splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma (SMZL) (World Health Organization designation) and treated with fludarabine followed by splenectomy with simultaneous liver biopsy. The pathologic analysis of the spleen revealed infiltration of red pulp by the critical cells without white pulp involvement, which is characteristic of HCL and HCL-V but not of SLVL (SMZL). This case illustrates an atypical marrow presentation of HCL-V and emphasizes the need to correlate all clinical and pathologic data, including tissue biopsy, in reaching a diagnosis.     

A case of amelanotic melanoma of the nasal cavity

A 68-year-old male visited Hospital A for treatment of epistaxis, his chief complaint. He was told that he had an easily-bleeding tumor in the nasal cavity. Based of biopsy, a diagnosis of amelanotic melanoma was made. Operation was performed for removal of the tumor. About 8 months after discharge, he visited Hospital B with complaints of lumbar pain and epistaxis. After biopsy at Hospital B, malignant lymphoma (diffuse large cell) was diagnosed, and the patient was referred to our hospital. On bone marrow puncture and biopsy, tumor cell infiltration was observed. Flow cytometric surface marker analysis revealed that these tumor cells were negative for CD45. Results of HE staining of the nasal cavity tumor were insufficient for diagnosis, and staining by immunohistochemistry was necessary to confirm the diagnosis. On immunohistochemical staining of the nasal cavity tumor tissue and bone marrow biopsy tissue, LCA, L26 and UCHL-1 were negative, and S-100 and HMB-45 positive. Recurrence of amelanotic melanoma accompanied by bone marrow infiltration was therefore diagnosed. The incidence of amelanotic melanoma with primary lesions in the nasal cavity is low. However, in making the diagnosis of a nasal cavity lesion, the possibility of such a melanoma should be kept in mind. In many cases, it is difficult to diagnose amelanotic melanoma with HE staining alone, and immunohistochemistry must be used.     

bcl-2 expression by multicolor flow cytometric analysis assists in the diagnosis of follicular lymphoma in lymph node and bone marrow

The expression of bcl-2, CD10, and CD20 was examined by multicolor flow cytometry in 78 samples including lymph node or other tissue biopsy specimens containing follicular lymphoma (FL; n = 17), reactive hyperplasia (RH; n = 28), or other malignant lymphomas (n = 20), as well as bone marrow aspirates (n = 13). The presence of CD10+ cells with high bcl-2 expression predicted the presence of FL rather than RH with a positive predictive value of 100% and negative predictive value of 96%. CD10+ cells with high bcl-2 expression also were found in a subset of diffuse large B-cell lymphomas and were otherwise rare in other types of malignant lymphoma. In contrast with immunohistochemical studies, a reduced but apparently measurable level of bcl-2 was present in benign follicular center cells. Hematogones showed lower bcl-2 levels than did FL cells in the bone marrow, and neutrophils were bcl-2-. Measurement of bcl-2 expression levels by multiparameter flow cytometry offers a rapid, quantitative assessment that may assist in the diagnosis of FL in lymph nodes or bone marrow, even when other CD10+ cells or admixed normal B cells are present.     

Hematolymphoid neoplasms are common in bone marrow biopsies performed for non-specific,diffuse marrow signal alterations on magnetic resonance imaging

AimsMRI is an imaging modality used for a wide range of clinical indications. Occasionally, non-specific, diffuse T1 marrow signal alterations are identified, which may prompt a bone marrow biopsy (BM). However, there is little data on the clinicopathologic significance of this signal alteration. This study evaluated the frequency and nature of pathologic findings in BM performed to evaluate diffuse MRI T1 marrow signal alterations.MethodsRecords from January 2003 to May 2015 were searched for BM performed to evaluate abnormal MRIs. 179 cases were identified. Patients with nodular/destructive bone lesions on MRI or other imaging studies, or a previous diagnosed metastatic tumor or hematologic malignancy were excluded, resulting in 45 cases.ResultsThe patients included 22 males and 23 females with a median age of 56 years. The location of the MRI T1 marrow signal alterations included spine, pelvis, knee, skull, femur, and arm. 19/45 patients had neoplasms identified in the BM. The remaining 26 patients had benign BM findings. There was a significant difference in hemoglobin values in patients with neoplastic versus benign BM findings (p = 0.037, unpaired Student's t-test).ConclusionsDiffuse T1 marrow signal alterations on MRI should warrant a BM evaluation, as 42% of cases showed an underlying hematolymphoid neoplasm or metastatic tumor, even when patients with a known history of malignancy were excluded. When faced with a BM from a patient with a non-specific, diffuse MRI signal alteration, a pathologist should have a high index of suspicion for a malignant neoplasm, most often of hematopoietic/lymphoid type.     

Primary desmoplastic small round cell tumor of bone: report of a case with cytogenetic confirmation

We report a case of desmoplastic small round cell tumor occurring in the right ilium of a 13-year-old boy. Morphologically, the neoplasm consisted of small round cells of primitive appearance with a diffuse growth pattern replacing marrow space and eroding bone. Immunohistochemical staining was positive for vimentin, synapsin, CD99 (MIC2 protein), and FLI-1, prompting an initial diagnosis of Ewing sarcoma/primitive neuroectodermal tumor. However, a diagnosis of desmoplastic small round cell tumor was rendered after the detection by cytogenetic analysis of the reciprocal chromosomal translocation, t(11;22)(p13;q12), which is uniquely associated with this tumor. This is the first documented instance of desmoplastic small round cell tumor arising in bone.     

Bone marrow metastases in disseminated alveolar rhabdomyosarcoma: case report with ultrastructural study and review.

A case of desseminated alveolar rhabdomyosarcoma in an 18-year-old male with leuco-erythroblastic anaemia is described. Numerous bizarre malignant cells, including frequent multinucleated giant cells, were seen in bone marrow aspirates, and osteolytic lesions appeared late in the clinical course. The primary site of the neoplasm remained undertermined during life and also at necropsy, which revealed minute pulmonary metastases and extensive lymph nodal, pleural and skeletal deposits. The diagnosis was confirmed on necropsy tissue by ultrastructural examination which demonstrated numerous thin (5 nm) and thick (15 nm) intracytoplasmic filaments in tumour cells, sometimes organized in bundles; scattered dense Z-band-like bodies, and rod-shaped structures were also seen. The fine structure of the rhabdomyosarcoma in the present case is compared with previous ultrastructural studies. Elongated, thick intracytoplasmic filaments whose diameter corresponds to that of myosin myofilaments are strong evidence for rhabdomyoblastic differentiation and are considered to be the sine qua non of a positive electron microscopic diagnosis of rhabdomyosarcoma. Orgaized bundles of filaments and Z-band-like dense bodies are usually present, and rod-shaped structures are found infrequently, but none of these are necessary for the ultrastructural diagnosis.     

Plastic embedded core biopsy: a complementary approach to bone marrow aspiration for diagnosing acute myeloid leukaemia.

Bone marrow aspirates and biopsy specimens were taken at diagnosis from 51 patients with acute myeloid leukaemia (AML). The diagnosis was based on morphological and cytochemical analyses, and the leukaemias were classified by FAB criteria. A considerable difference was observed between the results of bone marrow aspirates and the findings of plastic-embedded bone marrow biopsy specimens, particularly in marrow cellularity, extent of blast cell infiltration, and cell type involved in the leukaemic process. The myelomonocytic cell type seemed to predominate in the sections. In four cases there was considerable marrow infiltration with maturing, but dysplastic, granulocytic cells in the sections, but not in the aspirate smears. Features of potential prognostic importance, such as bone marrow infiltration with inflammatory cells, were easily recognised and quantified in the sections. These results indicate that plastic embedded bone marrow biopsy sections complement the findings of bone marrow aspiration in the diagnosis of AML and may also provide information of independent prognostic importance that cannot be obtained by other means.     

Contribution of Electron Microscopy of Cell Cultures to the Classification of Three Round Cell Sarcomas in Children

We have studied three round cell sarcomas from pediatric patients in tissue culture to compare the electron microscopic morphology of cells in culture to cells from original biopsy specimens. None of the original tumors displayed distinctive features by light microscopy that would allow classification of a specific tumor type, and electron microscopy was not helpful in identifying specific morphologic features that would allow further classification of tumor types. However, electron microscopy of cells in culture from the three neoplasms revealed distinctive morphologic features that did allow further classification of all three tumors. Cells from an inguinal lymph node, which were cultured in soft agar tumor colony-forming assay, revealed Z-bands and actin and myosin filaments indicative of a rhabdomyosarcomatous nature for the tumor. Cells from 5-day, 10-day, and 4-month cultures of a bone marrow metastasis of a second tumor revealed features of skeletal muscle in the young cultures and neuroblasts in the older culture, suggesting a primitive neuroectodermal neoplasm. Cultured cells from the third tumor, a neoplasm of the calf in an infant, displayed large lakes of glycogen, typical of cells of Ewing's sarcoma, which were not present in the cells examined from the original lesion. Ultrastructural studies of cells in culture have the potential to add morphologic data that may be useful to further define and classify a neoplasm, as illustrated in the 3 cases reported here.