Ajay Puri

CT-guided percutaneous core needle biopsy in deep seated musculoskeletal lesions : a prospective study of 128 cases

ObjectivesAlthough large lesions of the limbs can easily be biopsied without image guidance, lesions in the spine, paraspinal area and pelvis are difficult to target, and benefit from CT guidance to improve the accuracy of targeting the lesion for biopsy purposes. A prospective study of CT-guided core needle biopsies for deep-seated musculoskeletal lesions was conducted at a referral cancer institute over a 4-year period with the aim of assessing the safety and efficacy of the procedure.Patients & methodsFrom January 2000 to December 2003, 136 consecutive CT-guided biopsy sessions were undertaken for musculoskeletal lesions in 128 patients comprising 73 males and 55 females. The following data was recorded in all patients: demographic data, suspected clinicoradiological diagnosis, data related to core biopsy session (date, site, approach, total time required in minutes, number of cores, surgeon satisfaction with adequacy of cores), patient discomfort, complications, histopathology report and number of further sessions if material obtained during the first biopsy session was not confirmatory. The sample obtained during the biopsy session was considered inconclusive if, in the opinion of the pathologist, inadequate or non-representative tissue had been obtained. The diagnosis was considered inaccurate if the final histopathological diagnosis did not match with the biopsy diagnosis, or if subsequent clinicoradiological evaluation at follow up did not correlate with the biopsy diagnosis in those patients who were treated with modalities other than surgery.ResultsIn 121 patients, a single session was sufficient to obtain representative material, whilst for six patients two sessions, and for one patient three sessions were necessary. The time taken for biopsy, including the pre-biopsy CT examination time, varied from 15 min to 60 min (median 30 min). For 110 bony lesions 116 sessions were required, and for 18 soft-tissue lesions 20 sessions were required. 108 biopsy sessions yielded a diagnosis, whilst 28 were inconclusive (diagnostic yield of 79.41%). Of 108 diagnostic biopsies, five were considered inaccurate (accuracy rate of 95.37%). The overall diagnostic yield and accuracy rate for bony lesions were 81.03% and 95.74%; and those for soft-tissue lesions were 70% and 92.85%. There were two complications with no permanent sequelae.ConclusionCT-guided core needle biopsy is a safe, easy, and effective technique for the evaluation of deep-seated musculoskeletal lesions, with a high rate of diagnostic yield and accuracy. It facilitates definitive therapy without the patient having to undergo a major surgical procedure for diagnosis.

Revisiting Chordoma With Brachyury, a “New Age” Marker: Analysis of a Validation Study on 51 Cases

CONTEXT Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas. OBJECTIVE To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors. DESIGN Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry. RESULTS The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, respectively. Brachyury staining was positive in 46 of the 51 chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The dedifferentiated area in 2 chordomas was negative for brachyury staining. Fourteen of 15 chordomas with chondroid component showed positive brachyury staining. Immunohistochemical expression of other markers, included cytokeratin (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22 of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%). CONCLUSION Exclusive brachyury expression in more than 90% of chordomas indicates its value as a unique, specific marker with other sensitive markers like cytokeratin, epithelial membrane antigen, and/or S100 protein in substantiating a diagnosis of chordoma, including on small biopsies.

Monogenic and polygenic determinants of sarcoma risk: an international genetic study

BACKGROUND Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young. Outside rare syndromes, the nature, extent, and clinical significance of their genetic origins are not known. We aimed to investigate the genetic basis for bone and soft-tissue sarcoma seen in routine clinical practice. METHODS In this genetic study, we included 1162 patients with sarcoma from four cohorts (the International Sarcoma Kindred Study [ISKS], 966 probands; Project GENESIS, 48 probands; Asan Bio-Resource Center, 138 probands; and kConFab, ten probands), who were older than 15 years at the time of consent and had a histologically confirmed diagnosis of sarcoma, recruited from specialist sarcoma clinics without regard to family history. Detailed clinical, pathological, and pedigree information was collected, and cancer diagnoses in probands and relatives were independently verified. Targeted exon sequencing using blood (n=1114) or saliva (n=48) samples was done on 72 genes (selected due to associations with increased cancer risk) and rare variants were stratified into classes approximating the International Agency for Research on Cancer (IARC) clinical classification for genetic variation. We did a case-control rare variant burden analysis using 6545 Caucasian controls included from three cohorts (ISKS, 235 controls; LifePool, 2010 controls; and National Heart, Lung, and Blood Institute Exome Sequencing Project [ESP], 4300 controls). FINDINGS The median age at cancer diagnosis in 1162 sarcoma probands was 46 years (IQR 29-58), 170 (15%) of 1162 probands had multiple primary cancers, and 155 (17%) of 911 families with informative pedigrees fitted recognisable cancer syndromes. Using a case-control rare variant burden analysis, 638 (55%) of 1162 sarcoma probands bore an excess of pathogenic germline variants (combined odds ratio [OR] 1·43, 95% CI 1·24-1·64, p<0·0001), with 227 known or expected pathogenic variants occurring in 217 individuals. All classes of pathogenic variants (known, expected, or predicted) were associated with earlier age of cancer onset. In addition to TP53, ATM, ATR, and BRCA2, an unexpected excess of functionally pathogenic variants was seen in ERCC2. Probands were more likely than controls to have multiple pathogenic variants compared with the combined control cohort group and the LifePool control cohort (OR 2·22, 95% CI 1·57-3·14, p=1·2 × 10(-6)) and the cumulative burden of multiple variants correlated with earlier age at cancer diagnosis (Mantel-Cox log-rank test for trend, p=0·0032). 66 of 1162 probands carried notifiable variants following expert clinical review (those recognised to be clinically significant to health and about which patients should be advised), whereas 293 (25%) probands carried variants with potential therapeutic significance. INTERPRETATION About half of patients with sarcoma have putatively pathogenic monogenic and polygenic variation in known and novel cancer genes, with implications for risk management and treatment. FUNDING Rainbows for Kate Foundation, Johanna Sewell Research Foundation, Australian National Health and Medical Research Council, Cancer Australia, Sarcoma UK, National Cancer Institute, Liddy Shriver Sarcoma Initiative.

Decision making in primary sacral tumors

BACKGROUND CONTEXT Primary tumors of the sacrum are extremely rare lesions. Their management is governed by an interplay of complex factors. Appropriate decision making is crucial to obtain the best possible outcome in terms of maximizing disease control while attempting to minimize neurological dysfunction. PURPOSE Our study presents the results of a group of patients with primary tumors of the sacrum who were surgically treated by the same multidisciplinary team at a specialist oncology center over a relatively short period of time (5 years). STUDY DESIGN/SETTING Patients were identified by a retrospective review from a prospectively maintained database. PATIENT SAMPLE Between January 2000 and December 2005, 17 primary sacral tumors were surgically treated at our institution, a referral center for oncology. OUTCOME MEASURES We evaluated the outcome in terms of local disease control, residual neurological dysfunction, and complications as a result of surgical intervention. METHODS There were 12 males and 5 females. The diagnosis included chordoma in six patients, giant cell tumor in seven patients, aneurysmal bone cyst in two patients, and a chondrosarcoma and an osteoblastoma in one patient each. Sixteen of these patients were analyzed. Four lesions had their upper extent at S1, six lesions had their upper extent at S2, four lesions had their upper extent at S3, and two lesions were below S3. Ten cases were treated with wide excision and underwent partial sacral amputations. Five cases had a midline sacral amputation through S1, three through S2, and two through S3. Six benign lesions were treated with curettage. None of the patients received chemotherapy. Four cases received postoperative radiation. The follow-up duration ranged from 18 to 44 months with a mean of 31 months. RESULTS None of the six patients who presented with loss of bladder and bowel control regained it after surgery. Of the 10 patients who had intact bladder and bowel control preoperatively only 4 retained bladder and bowel control postoperatively. Of the six patients who lost bladder and bowel control postoperatively, four patients had a wide excision where bilateral S2 roots were sacrificed. The other two cases in whom the disease extended up to S1 had curettage. Local recurrence occurred in 4 of the 10 lesions treated with wide excision. All the patients who had inadequate margins recurred. Local recurrence occurred in two of the six lesions treated with curettage. Three of the four cases who received postoperative irradiation developed recurrence. Our wound complication rate was 13%. CONCLUSION Wide resection with adequate margins gives the best chance of local control and should be the surgery of choice for all malignant primary sacral tumors and in benign lesions involving lower segments when preservation of both S3 roots is possible. Intralesional curettage has a higher risk of local recurrence without providing the certainty of retaining neurological function. To retain bladder and bowel control and minimize neurological dysfunction, it may be worthwhile managing benign sacral tumors that extend above S3 with serial embolization. The administration of parenteral bisphosphonates may prove beneficial in cases of giant cell tumor managed with serial embolization.

Limb salvage surgery for osteosarcoma: effective low-cost treatment.

Successful management of osteosarcoma with limb salvage surgery is a challenging problem in the developing world. We report our early results with low-cost chemotherapy (without methotrexate) and low-cost limb salvage surgery. We prospectively collected data for 135 patients with histologically proven high-grade osteosarcoma of the extremities given neoadjuvant chemotherapy and treated with limb salvage surgery between January 2000 and February 2004. A locally designed and fabricated stainless steel customized megaprosthesis was used in 78 patients. Disease status and function was evaluated at followup ranging from 24 to 72 months. Followup data were available for 120 of the 135 patients. There were eight infections, four prosthesis breakages and three loosenings. Eighteen patients had local recurrence; 17 of these patients also developed lung metastases. Seventy-three patients (61%) were disease-free at followup. The group of 34 patients with 100% necrosis had better disease-free survival (79%). According to a modified Enneking system, the average functional score was 25.5 of 30 (85%) for the lower extremity and 20 of 30 (66%) for the shoulder. Our preliminary results suggest osteosarcoma can be managed well in a developing country in a cost-effective way. Limb salvage surgery has now become the standard of care.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Perioperative Interstitial Brachytherapy for Soft Tissue Sarcomas: Prognostic Factors and Long-Term Results of 155 Patients

BackgroundThe goal of this study was to evaluate the efficacy of temporary interstitial brachytherapy (BRT) for patients undergoing combined modality management of soft tissue sarcomas (STS).MethodsFrom January 1990 to December 2003, 155 adults 18–88 years of age (median = 42 years) with STS who had received BRT as part of locoregional treatment were included in this review. Sixty-four percent were males. Sixty-nine percent had primary lesions. Sixty percent had lesions involving the lower extremities. Spindle cell sarcoma (28%) and synovial sarcoma (16%) were the most common histologic types and 51% had grade III lesions. Treatment included wide local excision of primary tumor with BRT with or without external beam radiotherapy (EBRT).ResultsAfter a median followup of 45 months, the local control (LC), disease-free survival (DFS), and overall survival (OS) for the entire cohort was 71%, 57%, and 73%, respectively. DFS was superior for superficial tumors compared with that for deep tumors (96% vs. 54%, P =.02). Patients with a tumor less than 5 cm had superior OS (88% vs. 63%, P =.05). Cumulative radiotherapy dose greater than 60 Gy had a significant positive impact on LC (P = .003), DFS (P =.003), and OS (P =.048). Subcutaneous fibrosis (21%) was the major complication.ConclusionsTemporary perioperative iridium-192 interstitial BRT with or without EBRT after function-preserving surgery results in satisfactory outcome in patients with STS. Both low dose rate and high dose rate BRT are equivalent in terms of disease control and complications when used alone or in combination with EBRT. BRT results in fewer complications compared with the combination of BRT and EBRT.

Giant cell tumor of bone in children and adolescents.

Background: There are very few series that document giant cell tumor of bone (GCT) in the immature skeleton, and the reported incidence in literature varies from 1.8% to 10.6%. The purpose of this study was to document the incidence of GCT in patients with open physis in the Indian population and study the course of the disease with respect to its adult counterpart to see if it behaved any differently. Methods: Between January 2000 and December 2005, 17 (6%) of 285 surgically treated patients with histologically proven GCT had open physis on imaging. Treatment was directed toward local control without sacrificing joint function, with most lesions treated with intralesional curettage. Results Fourteen (82%) patients were girls. The most common site was around the knee (53%). Of 15 lesions in tubular bones, 13 were epiphysiometaphyseal in location. An open physis did not prevent GCT from penetrating the epiphyseal cartilage. Histologically, the tumors were typical of GCT. Of 15 patients available for follow-up, 3 (20%) developed local recurrence. Conclusions: Although the overall incidence of GCT may be higher in the Asian population, the percentage of skeletally immature patients or those nearing skeletal maturity is similar to that described in literature. The biological behavior of the disease is similar to that seen in adults, except a marked female preponderance, principles of treatment, recurrence patterns, and course of the disease mirror the behavior of its adult counterpart. Level of Evidence: Level IV, case series.

Alveolar soft part sarcoma 'revisited': clinicopathological review of 47 cases from a tertiary cancer referral centre, including immunohistochemical expression of TFE3 in 22 cases and 21 other tumours.

Background: Alveolar soft part sarcoma accounts for 0.5–1.0% of soft tissue sarcomas in the United States. At our Hospital, it constitutes 1.8% of the newly diagnosed soft tissue sarcomas. Lately, TFE3 has been found to be a useful immunohistochemical marker for diagnosing this sarcoma. Methods: We reviewed 47 cases of alveolar soft part sarcoma that were either treated at Tata Memorial Hospital, Mumbai, India, or were referred in consultation from various parts of India. TFE3 immunohistochemical staining was performed on 22 alveolar soft part sarcomas and on 21 other tumours. Results: Unlike most other large series, 58% of patients were males and 40% were females. The ages ranged from 2 to 54 years (median 24 years). Tumours were located in the deep soft tissues of lower extremities (54%), upper extremities (13%), head and neck (11%), retroperitoneum (10%), chest wall (6%), pelvis (4%), and were positive for TFE3 (20/22, 91%), desmin (3/18, 16%), myoglobin (1/6, 17%) and smooth muscle actin (1/9, 11%). TFE3 was positive in tumour controls that comprised paragangliomas (3/4), translocation related renal cell carcinoma (1/1), adrenocortical carcinoma (1/3) and granular cell tumour (1/3). Treatment consisted of primary surgical excision, metastatectomy, chemotherapy and radiotherapy. Seven tumours (24%) recurred locally and 21 of 29 (72%) metastasised, mainly to the lungs. Follow-up information (5–108 months, median 27.5 months) was available for 22 patients. No patients died in the relatively short follow-up period. Conclusions: TFE3 is a useful immunohistochemical marker for diagnosis of an alveolar soft part sarcoma. Awareness of other tumours expressing TFE3 is vital. Alveolar soft part sarcoma has a high metastasis rate but relatively good short-term survival. Surgical excision with follow-up forms the present management.

The outcome of the treatment of diaphyseal primary bone sarcoma by resection, irradiation and re-implantation of the host bone

We analysed the outcome of patients with primary non-metastatic diaphyseal sarcomas who had en bloc resection with preservation of the adjoining joints and reconstruction with re-implantation of sterilised tumour bone after extracorporeal radiation (50 Gy). Between March 2005 and September 2009, 32 patients (16 Ewings sarcoma and 16 osteogenic sarcoma) with a mean age of 15 years (2 to 35) underwent this procedure. The femur was the most common site in 17 patients, followed by the tibia in 11, humerus in three and ulna in one. The mean resected length of bone was 19 cm (10 to 26). A total of 31 patients were available at a mean follow-up of 34 months (12 to 74). The mean time to union for all osteotomy sites was 7.3 months (3 to 28): metaphyseal osteotomy sites united quicker than diaphyseal osteotomy sites (5.8 months (3 to 10) versus 9.5 months (4 to 28)). There were three local recurrences, all in soft-tissue away from irradiated graft. At the time of final follow-up, 19 patients were free of disease, one was alive with disease and 11 had died of disease. The mean Musculoskeletal Tumor Society Score for 29 patients evaluated at the last follow-up was 26 (9 to 30). Extracorporeal irradiation is an oncologically safe and inexpensive technique for limb salvage in diaphyseal sarcomas and has good functional results.

Rotationplasty for Bone Tumors: Is There Still a Role?

We evaluated the disease status and functional results in 30 patients (range, 6-25 years) who underwent rotationplasty for bone sarcomas from January 2000 to February 2004. Plating was used for fixation in all 27 distal femur resections. In the proximal femur tumor, the distal femur was contoured and fixed to the ilium with cancellous screws. In the two cases involving the entire femur, the upper end of the tibia was articulated with the acetabulum in one case and an Austin Moore prosthesis was inserted in the upper end of the tibia in the other. Two patients underwent an amputation after postoperative vascular compromise. Other complications included venous congestion in two patients, who recovered after exploration, partially recovered nerve palsy in one, wound infection in two, local recurrence in one, and nonunion with subsequent bone grafting in one. Functional evaluation was documented in 26 patients with a followup ranging from 24 to 60 months. Using the Musculoskeletal Tumor Society scoring system, the score was 25 or greater in 20 of 26 patients. In appropriately indicated cases, rotationplasty provides good local disease control and good function.Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.