Bone marrow biopsy in the initial staging of Ewing sarcoma: Experience from a single institution.

BACKGROUND: Ewing sarcoma (ES) is the second most common bone tumor in adolescents and children. Staging workup for ES includes imaging and bone marrow biopsy (BMB). The effective role of BMB is now under discussion. PROCEDURE: A monoinstitutional retrospective analysis reviewed clinical charts, imaging, and histology of patients with diagnosis of ES treated at the Rizzoli Institute between 1998 and 2017. RESULTS: The cohort included 504 cases of ES of bone; 137 (27%) had metastases at diagnosis, while the remaining 367 had localized disease. Twelve patients had a positive BMB (2.4%). Eleven had distant metastases detected at initial workup staging with imaging assessment: six patients presented with bone metastases, five with both bone and lung metastases. Only one patient with ES of the foot (second metatarsus) was found to have bone marrow involvement with negative imaging evaluation (0.3%). CONCLUSIONS: On the basis of our data, we suggest reconsidering the effective role of BMB in initial staging workup for patients with ES with no signs of metastases by modern imaging techniques. In metastatic disease, the assessment of the bone marrow status may remain useful to identify a group of patients at very high risk who could benefit from different treatment strategies.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

BACKGROUND: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. METHODS: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. RESULTS: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). CONCLUSIONS: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Bone marrow metastasis in primary bronchial mucoepidermoid carcinoma: a case report.

Primary bronchial mucoepidermoid carcinoma in the lung is relatively rare. It rarely presents with the highly malignant biological characteristic of bone marrow metastasis. We describe a case of this disease with bone marrow metastasis. A 56-year-old man with the primary manifestation of bone pain and bloodstained sputum had two abnormal shadows on the left inferior lobar bronchus and peripheral tissue of the lower lobe of the left lung, respectively. Computed tomography-guided percutaneous puncture biopsy and bone imaging confirmed the diagnosis of high-grade bronchial mucoepidermoid carcinoma with bone metastasis. However, the patient soon presented with progressive hemoglobin and platelet decline and severe multi-organ hemorrhage. Subsequently, we performed bone marrow aspiration and biopsy, which revealed malignant cells and necrosis. The patient deteriorated rapidly from the disease, and died on the 16th day of admission. We hope that this case report will increase awareness of the possibility of primary high-grade bronchial mucoepidermoid carcinoma metastasizing to the bone marrow, which might be a poor prognostic factor.

Sagittal mandibular osteotomy for removal of intraosseous lesion.

The ramus sagittal split osteotomy or mandibular body is an established technique for correction of dentofacial deformities but can have an accurate indication in cases requiring surgical access to remove lesions or more teeth included in the region of the mandibular angle. The main advantages of this technique are the possibility of preservation of the inferior alveolar nerve bundle and significant reduction in postoperative morbidity. In this article, the authors show a case in which the sagittal osteotomy of the mandible was used to gain access for removal of a lesion (complex odontoma).

Pooled analysis of the prognostic relevance of disseminated tumor cells in the bone marrow of patients with ovarian cancer.

OBJECTIVE: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer. MATERIALS AND METHODS: Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs. RESULTS: Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 × 106 mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37-65 months vs 33 months; 95% confidence interval, 23-43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival. CONCLUSIONS: Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.

Metal-backed versus all-polyethylene tibias in megaprostheses of the distal femur.

In megaprostheses, the tibial component is rarely a source of failure. The evolution of these implants has followed standard arthroplasty trends moving from majority use of all-polyethylene tibias (APT) to high volume use of metal-backed tibial (MBT) components. We report the results of 72 endoprostheses using either MBT (n = 42) or APT (n = 30) implanted between 1994 and 2006. Failures of the implant related to the tibial component were isolated, and 5-year survival of the tibial implant of the MBT cohort was 94%, and for the APT cohort, 87% (P = .39). The difference in tibial component failures between the 2 groups was not statistically significant (Pearson χ(2) = 0.1535, P = .6952). Revision rates for the entire implant and infection rates were not significantly different between the 2 groups.

Genetic diagnosis of alveolar rhabdomyosarcoma in the bone marrow of a patient without evidence of primary tumor.

Alveolar rhabdomyosarcoma (ARMS) is characterized by two pathognomonic translocations, both involving the FOXO1 gene. We describe a case of a 10-year-old child with multiple lytic lesions involving all the vertebral bodies, sternum and femur and a bone marrow biopsy compatible with a small round cell neoplasia, but no evidence of a primary tumor. Interphase FISH analysis with specific probes evidenced a rearrangement involving the FOXO1 gene and RT-PCR identified the PAX7-FOXO1 fusion transcript. These data show a case of ARMS with no evidence of primary tumor presenting the PAX7-FOXO1 fusion gene.

Isolated gingival relapse of acute lymphoblastic leukemia after transplantation.

A patient with a history of precursor B-cell leukemia presented with an isolated ulcerating gum lesion 8 years after allogeneic stem cell transplantation with severe graft versus host disease. A biopsy revealed an undifferentiated malignant hemic lesion. Examinations of the peripheral blood and marrow were normal. Molecular studies confirmed clonal relationship between the gum lesion with the original marrow disease, despite the anatomical, histological and chronological separations.

[A case of gastric cancer accompanied by disseminated carcinomatosis of bone marrow with DIC recovered by sequential therapy consisting of MTX and 5-FU].

A 78-year-old male was admitted to our hospital complaining of anorexia. Endoscopy revealed gastric cancer with pyloric stenosis and MRI showed multiple metastasis of thoracic vertebral body. Blood examinations showed DIC and CEA was 118.3 ng/mL. Sternum bone marrow biopsy revealed poorly-differentiated adenocarcinoma. Chemotherapy with sequential therapy consisting of MTX and 5-FU (MTX 150 mg/body, 5-FU 1,000 mg/body) was performed in addition to anti-DIC therapy. After 3 courses, DIC was resolved. Then, we changed the chemotherapy regimen to S-1/ paclitaxel (S-1 60 mg/body, PTX 60 mg/body). After 2 courses, the primary tumor was remarkably reduced and CEA decreased to within normal limits. After discharge, the patient has been undergoing chemotherapy on an outpatient basis.

[A case of disseminated bone marrow carcinosis with disseminated intravascular coagulation successfully controlled with S-1 after total gastrectomy for advanced gastric cancer].

Bone marrow carcinosis due to gastric cancer with disseminated intravascular coagulation(DIC)occurs suddenly, progresses rapidly, and has a very poor prognosis. In addition, physical status tends to be bad at the time of the episode, and palliative care is generally selected as the treatment method. The case was a 70-year-old woman who underwent total gastrectomy for scirrhous stomach cancer five years previously. She recently noticed gingival hemorrhage, and was referred to our hospital by a nearby doctor. As a result of her examination, she was diagnosed with disseminated bone marrow carcinosis as a postoperative recurrence of gastric cancer that resulted in DIC. We transfused blood platelets and fresh frozen plasma into her, and controlled the bleeding tendency temporarily. She was started on oral administration of S-1 for improvement of DIC, and the therapy was successful without loss of QOL. It is easy to continue S-1 therapy as chemotherapy in the outpatient department, because it is a matter of internal medicine.

Prognostic Significance of FDG Uptake of Bone Marrow on PET/CT in Patients With Non-Small-Cell Lung Cancer After Curative Surgical Resection.

BACKGROUND: This study evaluated the relationship between 18F-fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography (PET)/computed tomography (CT) imaging and serum inflammatory markers and assessed the prognostic value of FDG uptake of BM in patients with non-small-cell lung cancer (NSCLC) who underwent curative surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 110 NSCLC patients who underwent FDG PET/CT imaging and subsequent curative surgical resection. The maximum standardized uptake value of NSCLC (Tmax), mean FDG uptake of BM (BM SUV), and BM to liver uptake ratio (BLR) were measured. The relationships between BM SUV, BLR, and serum inflammatory markers were evaluated and the prognostic significance of PET/CT parameters for predicting recurrence-free survival (RFS) and overall survival (OS) were assessed. RESULTS: BM SUV and BLR were significantly associated with serum C-reactive protein (CRP) level, white blood cell count, and the neutrophil to lymphocyte ratio (NLR). BLR was also significantly correlated with serum albumin and the platelet to lymphocyte ratio. In univariate analysis, tumor, node, metastases (TNM) stage, serum CRP level, NLR, Tmax, and BLR were significant prognostic factors for RFS and OS, whereas histopathology and tumor size were significant prognostic factors for RFS. In multivariate analysis, BLR, histopathology, TNM stage, and Tmax were independent prognostic factors for RFS and TNM stage and Tmax were independent prognostic factors for OS. CONCLUSION: FDG uptake of BM on PET/CT imaging was correlated with serum inflammatory markers and was an independent predictor for RFS, along with FDG uptake of NSCLC.

Recent advances in the mangement of multiple myeloma.

The management of multiple myeloma has undergone a major change during the past decade. Currently, patients < 65 years of age with advanced disease (stage II-III) are best treated with initial chemotherapy (3-4 cycles of vincristine, adriamycin and dexamethasone, or vincristine, adriamycin and methyl prednisolone, or thalidomide and dexamethasone followed by high dose chemotherapy with autologous peripheral blood stem cell transplantation. More than 50% of patients achieve complete response following this approach. The results of a number of nonrandomized and randomized studies indicate that treatment with high dose chemotherapy followed by autologous peripheral blood stem cell transplantation is associated with improved overall and event-free survival compared with conventional chemotherapy. The absence of chromosome 13 abnormalities, serum albumin levels > 3.5 g/dl and low serum b-2 microglobulin are associated with a better outcome. Almost all patients with significant bone disease or osteoporosis are candidates for therapy with bisphosphonates. About one-third of patients with relapsed or refractory myeloma benefit from therapy with thalidomide or bortezomib (a proteosome inhibitor). Recent work in the immunotherapy of myeloma suggests that some novel immune-based approaches might be useful in the management. The application of cytogenetics and molecular genetics, especially gene expression profiling, are likely to be areas of active research in future studies.

Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy.

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important. PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients' prognosis. RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P =.032 and P =.014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.

Comparison between Use of PSA Kinetics and Bone Marrow Micrometastasis to Define Local or Systemic Relapse in Men with Biochemical Failure after Radical Prostatectomy for Prostate Cancer.

BACKGROUND: Treatment of biochemical failure after radical prostatectomy for prostate cancer is largely empirically based. The use of PSA kinetics has been used as a guide to determine local or systemic treatment of biochemical failure. We here compared PSA kinetics with detection of bone marrow micrometastasis as methods to determine local or systemic relapse. MATERIALS AND METHODS: A transversal study was conducted of men with biochemical failure, defined as a serum PSA >0.2ng/ml after radical prostatectomy. Consecutive patients having undergone radical prostatectomy and with biochemical failure were enrolled and clinical and pathological details were recorded. Bone marrow biopsies were obtained from the iliac crest and touch prints made, micrometastasis (mM) being detected using anti-PSA. The clinical parameters of total serum PSA, PSA velocity, PSA doubling time and time to biochemical failure, age, Gleason score and pathological stage were registered. RESULTS: A total of 147 men, mean age 71.6 ± 8.2 years, with a median time to biochemical failure of 5.5 years (IQR 1.0-6.3 years) participated in the study. Bone marrow samples were positive for micrometastasis in 98/147 (67%) of patients at the time of biochemical failure. The results of bone marrow micrometastasis detected by immunocytochemistry were not concordant with local relapse as defined by PSA velocity, time to biochemical failure or Gleason score. In men with a PSA doubling time of < six months or a total serum PSA of >2,5ng/ml at the time of biochemical failure the detection of bone marrow micrometastasis was significantly higher. CONCLUSIONS: The detection of bone marrow micrometastasis could be useful in defining systemic relapse, this minimally invasive procedure warranting further studies with a larger group of patients.

Intracranial spread of Merkel cell carcinoma through intact skull.

We report an unusual case of Merkel cell carcinoma presenting as a frontal scalp mass with apparent invasion into underlying brain parenchyma through grossly intact calvaria. Despite wide local excision, craniectomy, intracranial tumor resection, and postoperative adjuvant irradiation, widespread systemic metastases resistant to chemotherapy developed, and the patient died 9 months after surgery. This case report confirms that Merkel cell carcinoma of the head and neck, already known to be an aggressive tumor, has the capacity for rapid intracranial extension. We propose that in this case, the mechanism of intracranial metastasis was via communicating veins rather than through bone destruction or systemic metastasis. Appropriate preoperative imaging should be carried out to define the extent of this tumor when it is adjacent to the skull. We found contrast-enhanced magnetic resonance imaging to be superior to computed tomography for defining soft tissue extent and marrow space involvement within underlying bone.

Detection of breast cancer cells in the bone marrow or peripheral blood: methods and prognostic significance.

Tumor cells can reach every anatomic district, organ and tissue through the peripheral blood circulation. Tumor cell shedding is considered an early event in the multi-phase process of metastasis, and the possibility of detecting tumor cells in the bloodstream and/or bone marrow before clinical evidence of distant metastases needs to be explored. The use of new sophisticated diagnostic and investigative techniques has boosted the study of tumor cell contamination of bone marrow and peripheral blood. Molecular techniques, such as reverse-transcriptase polymerase chain reaction, may be useful tools to reach this target, but, today, immunocytochemistry is still considered the gold standard to assess new techniques to detect isolated tumor cells in hematopoietic tissue. Little is known about the biology of isolated tumor cells in the peripheral blood or bone marrow. Two crucial points need to be evaluated: the identification of specific markers of breast cancer cells with clonogenic potential and their biologic properties, and the prognostic impact of the detection of isolated tumor cells in the bone marrow or peripheral blood stem cell collections.

[Solitary extra-bone-marrow form of plasmacytoma: diagnostic difficulties]. / Odosobniona pozaszpikowa postac szpiczaka plazmocytowego--trudnosci diagnostyczne.

We present the patient with soft tissue tumor, which in histopathological examination proved to be plasmacytoma. Initial laboratory and radiological diagnostics did not suggest recognition.

Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report.

BACKGROUND: While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/µl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions. CASE PRESENTATION: Massive neutrophil leukocytosis of approximately 100,000/µl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma. A bone marrow trephine biopsy revealed massively increased granulopoiesis, but no evidence of monoclonal myeloproliferative disease. After the primary tumor had been resected, white blood count (WBC) plummeted and went back to nearly normal levels within one week. With progressive metastatic disease, granulocyte colony-stimulating factor (G-CSF) plasma levels were found to be increased by 10-fold. White blood count (WBC) strictly correlated with tumor burden and response to chemotherapy. In the final stage of treatment resistent disease, white blood count (WBC) approximated 300,000/µl. CONCLUSION: We report on a granulocyte colony-stimulating factor (G-CSF) secreting undifferentiated endometrial sarcoma, which was associated with extreme neutrophil counts. White blood count (WBC) were closely correlated with tumor burden and associated with an aggressive clinical course. We suggest that paraneoplastic neutrophilia represents a poor prognostic sign in soft tissue sarcoma. In patients with similar constellations, antitumor therapy must not be delayed.