T-cell lymphoma with rhabdomyolysis: case report and literature review

Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.

Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma

The records of 63 high-risk neuroblastoma patients with bone marrow (BM) tumors at diagnosis were retrospectively reviewed. All patients received nine cycles of induction chemotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). Follow-up BM examination was performed every three cycles during induction chemotherapy and every three months for one year after the second HDCT/auto-SCT. BM tumor cells persisted in 48.4%, 37.7%, 23.3%, and 20.4% of patients after three, six, and nine cycles of induction chemotherapy and three months after the second HDCT/auto-SCT, respectively. There was no difference in progression-free survival (PFS) rate between patients with persistent BM tumor and those without during the induction treatment. However, after tandem HDCT/auto-SCT, the PFS rate was worse in patients with persistent BM tumor than in those without (probability of 5-yr PFS 14.7% +/- 13.4% vs. 64.2% +/- 8.3%, P = 0.009). Persistent BM tumor during induction treatment is not associated with a worse prognosis when intensive tandem HDCT/auto-SCT is given as consolidation treatment. However, persistent BM tumor after tandem HDCT/auto-SCT is associated with a worse prognosis. Therefore, further treatment might be needed in patients with persistent BM tumor after tandem HDCT/auto-SCT.

Morfología dual de células de mieloma: inusual presentación de un caso / Unusual presentation of plasma cell myeloma

Una mujer de 41 años consultó por dolor facial. En una resonancia magnética nuclear se observó una masa en el ápex del peñasco derecho. La biopsia mostró una infiltración difusa por células grandes atípicas con morfología plasmablástica, positivas para CD138, BCL6, CD56 y p53, con expresión monoclonal de cadena liviana kappa y factor de proliferación del 80%, planteando el diagnóstico diferencial entre linfoma plasmablástico versus plasmocitoma plasmablástico. Un mapeo óseo evidenció múltiples lesiones osteolíticas en cráneo; el proteinograma reveló hipogamaglobulinemia y la inmunofijación en suero y orina fueron negativas. Se realizó biopsia de médula ósea donde se observó infiltración en un 30% del cilindro óseo por células plasmáticas maduras monoclonales para kappa, con expresión focal de p53 y negativas para CD56. Estos hallazgos confirmaron el diagnóstico de mieloma múltiple. Este caso pone de manifiesto la existencia de un espectro morfológico de las neoplasias de células plasmáticas, mostrando una evolución clonal continua con una plasticidad adquirida para desdiferenciarse, volverse inmaduras e infiltrar tejidos extramedulares, posiblemente debido a acumulación de alteraciones moleculares. Por lo tanto, se evidencia la dificultad del diagnóstico diferencial histopatológico entre linfoma plasmablástico y transformación plasmablástica de mieloma múltiple, debido a sus perfiles inmunohistoquímicos casi idénticos.

A 41 year-old woman consulted because of facial pain. A magnetic resonance imaging showed a mass in the right petrous apex. A biopsy revealed a diffuse proliferation of large atypical cells with plasmablastic appearance, positive for CD138, BCL6, CD56 and p53. The proliferation factor was 80%. Monoclonal kappa light chain expression was observed. Because the unusual clinicopathological features the patient was studied to rule out systemic plasma cell myeloma. Bone scan disclosed multiple cranium osteolytic lesions; proteinogram showed hypogammaglobulinemia and immunofixation in serum and urine were negative. Afterwards, bone marrow biopsy was performed and it presented a 30% infiltration of the bone cylinder by mature plasma cells. These were monoclonal for kappa light chain with focal expression of p53 and without expression of CD56. These findings suggested the diagnosis of multiple myeloma. This case proposes a morphological spectrum of plasma cell neoplasms, showing a continuous clonal evolution of tumor cells, with an acquired plasticity of dedifferentiate, become immature and infiltrate extramedullary tissues, a fact possibly determined by accumulation of multiple genetic alterations. These findings confirm the difficulty of the differential diagnosis from histopathology study between plasmablastic lymphoma and plasmablastic transformation of plasma cell myeloma because of the nearly identical immunohistochemical profiles.

JAK2-positive Philadelphia-negative myeloproliferative neoplasms.

The recent discovery of the JAK2 mutations has rekindled interest in the approach to classic BCR/ABL-negative myeloproliferative neoplasms (MPNs) in terms of both diagnostic evaluation and treatment. However, additional clinical, laboratory and histological parameters play a key role to allow diagnosis and subclassification, regardless of whether JAK2 V617F mutation is present or not. Here are two cases which incidentally presented with splenomegaly and moderate leukocytosis, and were diagnosed as MPN-primary myelofibrosis (PMF) in prefibrotic phase and polycythemia vera (PV), respectively, using revised World Health Organization (WHO) 2008 criteria.

Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

OBJECTIVE: To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. MATERIALS AND METHODS: Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic myeloid leukemia (n = 7), and non-Hodgkin lymphoma (n = 2). Twenty subjects whose spinal MRI was normal, made up the control group. Peak enhancement percentage (Emax), enhancement slope (ES), and time to peak (TTP) were determined from a time-intensity curve (TIC) of lumbar vertebral bone marrow. A comparison between baseline and follow-up MR images and its histological correlation were evaluated in 10 patients. The infiltration grade of hematopoietic marrow with plasma cells was evaluated by a histological assessment of bone marrow. RESULTS: Differences in Emax, ES, and TTP values between the control group and the patients with diffuse bone marrow infiltration were significant (t = -11.51, -9.81 and 3.91, respectively, p 0.05). A positive correlation was found between Emax, ES values and the histological grade of bone marrow infiltration (r = 0.86 and 0.84 respectively, p < 0.01). A negative correlation was found between the TTP values and bone marrow infiltration histological grade (r = -0.54, p < 0.01). A decrease in the Emax and ES values was observed with increased TTP values after treatment in all of the 10 patients who responded to treatment (t = -7.92, -4.55, and 5.12, respectively, p < 0.01). CONCLUSION: DCE-MRI of spine can be a useful tool in detecting diffuse marrow infiltration of hematological malignancies, while its parameters including Emax, ES, and TTP can reflect the malignancies' histological grade.

Massive bone marrow involvement by clear cell variant of rhabdomyosarcoma.

A 16-year-old boy with generalized myalgia and petechial hemorrhage was found to have a diffuse infiltrative disease in his bone marrow (BM). The BM aspirate contained a dense population of vacuolated blast-like cells. The BM biopsy displayed compact sheets of small round cells with clear cytoplasm, reminiscent of Ewing sarcoma. Immunostains were not diagnostically conclusive while transmission electron microscopy on the BM cells demonstrated a clear skeletal muscle differentiation. The morphologic findings led to a tentative designation of metastatic embryonal rhabdomyosarcoma (RMS). It was not until cytogenetic analysis revealed the specific translocation t(2;13)(q35;q14) did the alveolar RMS finally get confirmed. Despite an exhaustive search by imaging studies, a primary tumor was not detected. This case illustrates that the massive BM involvement by atypical alveolar RMS of unknown origin may pose serious diagnostic challenges. Multidisciplinary studies are required to reach a definitive diagnosis.

Multiple myeloma presenting with coexisting severe marrow hypoplasia.

A 68-year-old man was referred to us with clinical and bone marrow (BM) features compatible with aplastic anemia. The correct diagnosis, hypoplasia of the BM coexisting with multiple myeloma, became apparent after noting rouleaux in the peripheral blood (PB) and approximately 50% plasma cells in the touch imprint of one of the two BM biopsies done. As standard therapy was precluded, the patient was put on dexamethasone but died within 4 days. This first case of the coexistence of untreated myeloma with aplastic BM shows that even apparently straightforward hypoplasia seen on the BM biopsy should be interpreted in conjunction with the PB smear and the BM touch imprint findings. Among other things, the BM biopsy and imprint should be repeated if the PB has findings such as rouleaux that do not fit with straightforward aplastic anemia. The combination of myeloma and BM aplasia precludes standard therapy and is rapidly fatal.

Cáncer de mama detección de células tumorales aisladas en médula ósea: relación con factores pronósticos / Breast cancer detection of isolated tumor cells in osseous: medulla relation with prognostic factors

La presencia de células tumorales en médula ósea en pacientes con cáncer de mama no metastático ha sido reportada en la literatura internacional, sin embargo, su valor pronóstico no está claro. El presente es el primer estudio nacional dirigido a determinar la incidencia de este hallazgo en nuestros pacientes y establecer su significado al relacionarlo con factores pronósticos conocidos. Se analizó la médula ósea de 40 pacientes con cáncer de mama no metastático que acudieron a la consulta de patología mamaria del Instituto Oncológico “Dr. Luis Razetti” entre enero de 2005 y abril de 2006. Las muestras fueron analizadas con hematoxilina-eosina e inmunohistoquímica con la aplicación de anticuerpos anticitoqueratina y se determinó la relación entre la presencia de células tumorales asiladas en médula ósea y los factores pronósticos conocidos. De las pacientes estudiadas, un 8 por ciento presentaron células tumorales aisladas en médula ósea; y este hallazgo se relacionó desde el punto de vista estadístico con el tamaño tumoral, estadio de la enfermedad, estado de los receptores hormonales. Durante el seguimiento de estas pacientes no se evidenció recaída sistémica. En pacientes con cáncer de mama no metastático es posible detectar células tumorales aisladas en aspirados de médula ósea y este hallazgo parece estar relacionado con factores pronósticos conocidos. Sin embargo, el impacto de este nuevo elemento evaluado en el pronóstico de las pacientes y su utilidad en la toma de decisiones terapéuticas está por definirse.

The presence of isolated tumor cells in non metastatic breast cancer patients has been reported in the international literature, however its prognostic values is actually not clear. The present work is the first national report to determinate these find and his incidence in our patients, the objetive was to determine the relationship between this isolated tumour cells and the knowing prognostic factors. We analyzed the bone marrow of 40 patients with non metastatic breast cancer whom accede to the breast cancer department consult of the “Dr. Luis Razetti” Oncology Institute, between the years January 2005 and April 2006. The specimens were analized with hematoxilin-eosin and an inmunohystochemistry with the application of the anticytokeratin antiboides and the determination of the relationship between the presence of isolated tumor cells and known prognostic factors was established. Of the studied patients the bone marrow study reported isolated tumour cells in 8 % of the patients and this finding was statistically related with the tumour size, the pathological stage and the hormonal receptors status. During the following time no systemic recurrence was reported in our patients. In patients with non metastatic breast cancer it is possible to detect isolated tumor cells in bone marrow and this finding seems to be related with some known prognostic factos, however the impact of this new element in the prognosis of the patients and its utility in the therapeutic decisions making needs to be defined.

Persistent Anemia in a Patient with Diffuse Large B Cell Lymphoma: Pure Red Cell Aplasia Associated with Latent Epstein-Barr Virus Infection in Bone Marrow

We report a case of pure red cell aplasia (PRCA), which was initially suspected as a result of bone marrow involvement of diffuse large B cell lymphoma. Persistent anemia without an obvious cause was observed in a 47-yr-old man diagnosed with relapsed diffuse large B cell lymphoma. The bone marrow study showed only erythroid hypoplasia without the evidence of bone marrow involvement with lymphoma cells, thus PRCA was suggested. However, parvovirus infection was excluded as a potential cause of PRCA because of negative IgM anti-parvovirus B19 antibody and negative parvovirus PCR in the serum. Latent Epstein-Barr virus (EBV) infection of bone marrow was suggested by in situ hybridization with EBV-encoded small RNA (EBER) that showed a strong positive expression in bone marrow cells. Thus, PRCA was thought to be associated with latent EBV infection in bone marrow cells. Although the finding of unexplained anemia is a possible predictor of bone marrow involvement with lymphoma cells, PRCA as a result of a viral infection including EBV should be considered in lymphoma patients. This is the first report of the occurrence of PRCA associated with latent EBV infection in a patient with non-Hodgkin's lymphoma.

Diffusion-Weighted Imaging with Sensitivity Encoding (SENSE) for Detecting Cranial Bone Marrow Metastases: Comparison with T1-Weighted Images

OBJECTIVE: This study was designed to determine whether diffusion-weighted imaging (DWI) with sensitivity encoding (SENSE) could detect bone marrow involvement in patients with cranial bone marrow (CBM) metastases. DWI results obtained were compared with T1-weighted imaging (T1WI) findings. MATERIALS AND METHODS: DWI with sensitivity encoding (SENSE; b value = 1,000) was performed consecutively in 13 patients with CBM metastases diagnosed pathologically and radiologically. CBM lesions were dichotomized according to the involved site, i.e., skull base or calvarium. Two radiologists qualitatively evaluated the relative conspicuousness of CBM lesions and image qualities in B0 and in isotropic DWI and in T1WI. According to region of interest analysis of normal and pathologic marrow for these three sequences, absolute signal difference percentages (SD%) were calculated to quantitatively analyze lesion contrast. RESULTS: All 20 lesions in 13 patients with CBM metastases revealed abnormal DWI signals in areas corresponding to T1WI abnormalities. Both skull base and calvarial lesions provided better lesion conspicuousness than T1WI and B0 images. Although the image quality of DWI was less satisfactory than that of T1WI, relatively good image qualities were obtained. Quantitatively, B0 images (SD%, 82.1+/-7.9%) showed better lesion contrast than isotropic DWI (SD%, 71.4+/-13.7%) and T1WI (SD%, 65.7+/-9.3%) images. CONCLUSION: For scan times of less than 30 seconds, DWI with SENSE was able to detect bone marrow involvement, and was superior to T1WI in terms of lesion conspicuity. DWI with SENSE may be helpful for the detection of cranial bone/bone marrow metastases when used in conjunction with conventional MR sequences.

Small cell carcinoma of the ovary presenting as bone marrow metastasis: a rare presenting feature.

Small cell carcinoma (SCC) of ovary-hypercalcaemic type is a rare cancer of young pre-menopausal women of unclear histogenesis. Bone metastasis and bone marrow infiltration by ovarian carcinomas is a rare feature and only a few case reports are available in the literature. Herein we report a case of small cell carcinoma-hypercalcaemic type of both the ovaries with bone marrow infiltration and features of metastatic calcification in various organs.

Bone marrow metastasis in solid tumors.

Bone marrow examination has been increasingly useful in documenting metastatic involvement of tumors. A retrospective analysis of 73 cases of bone marrow metastasis of solid tumors revealed 27 cases in the pediatric age group and 46 cases in the adult age group. All 27 pediatric cases were that of neuroblastoma. In the adult bone marrow metastasis from carcinoma prostate were present in 22 cases followed by carcinoma breast in 13 cases. Rest were 5 cases of carcinoma lung, 4 cases of carcinoma colon, 1 case each of carcinoma thyroid and renal cell carcinoma. A number of associated features were observed which may help to suggest bone marrow metastasis, in the absence of tumor cells in the bone marrow.

Bone marrow involvement in a primary mediastinal extragonadal non-seminomatous germ cell tumour.

A case of primary mediastinal extragonadal germ cell tumour with involvement of bone marrow, a rare finding, is reported with a review of literature.

Malignant melanoma metastatic to bone marrow.

Bone marrow aspiration and biopsy is a useful means of detecting systemic involvement in patients with non haematological malignancy. Metastases of malignant melanoma may be detected in the bone marrow in a small percentage of patients. Two cases of malignant melanoma, with metastasis to marrow at the time of presentation, are described. In one case, bone marrow was the first site where the malignancy was identified. Subsequent investigations revealed an anal melanoma. In the second case, the patient had widespread dissemination from a tonsillar melanoma to many organs of the body, including bone marrow.

Simultaneous occurrence of Hodgkin's disease and chronic lymphocyte leukemia: a unique presentation

Chronic lymphocytic leukemia (CLL) is a chronic, low-grade hematologic malignancy that can transform to a large cell non-Hodgkin's lymphoma (Richter's syndrome), which is associated with an unfavorable prognosis. A distinct Hodgkin's disease subgroup of lymphomatous CLL transformation has been well characterized. We describe a patient presenting with simultaneous manifestations of CLL and Hodgkin's disease. This patient is unique, presenting with separate sites of involvement of each disease within the same organ, in this case the bone marrow. The morphologic and immunohistochemical findings at diagnosis are correlated with the findings of the postmortem examination