ANZ J. Surg. 2003; 73: 26–30
ORIGINAL ARTICLE ORIGINAL ARTICLE
EXTRA-NODAL LYMPHOMA PRESENTING AS A MIMIC OF SOFT-TISSUE SARCOMA BRETT KNOWLES* AND JONATHAN W. SERPELL*† *Department of Surgery, Alfred Hospital and †Department of Surgery, Frankston Hospital, Monash University, Victoria, Australia
Background: A variety of soft-tissue tumours result in soft-tissue masses, which are all differential diagnoses of soft-tissue sarcomas. A rare cause is extra-nodal lymphoma which, unlike a soft-tissue sarcoma which it mimics, should not be excised, but rather treated by chemotherapy and/or radiotherapy. The aim of the present study was to identify clinical, radiological, biopsy and management features of lymphoma when presenting as a soft-tissue mass. Methods: A review of 17 cases of soft-tissue lymphoma presenting as a soft-tissue mass from a total database of 295 soft-tissue tumours was undertaken. Lymphomas arising in cervical, axillary and inguinal nodes were excluded. Results: All patients presented with a soft-tissue mass but none had the symptoms of lymphoma. Computed tomography scanning identified seven (54%) of 13 with regional lymphadenopathy, six (46%) of 13 with encasement of major vascular structures and three with invasion across major soft-tissue boundaries. Core biopsy established a diagnosis in 13 patients (sensitivity 93%). All patients were treated with either chemotherapy and/or radiotherapy and all are alive with a mean follow up of 19 months. None underwent major resectional surgery. Conclusion: The present series highlights a rare subgroup of patients with extra-nodal soft-tissue lymphoma mimicking soft-tissue sarcoma. Core biopsy is accurate in their diagnosis. Computed tomography scanning may show features suggesting the diagnosis. Key words: cancer, core biopsy, CT scanning, extra-nodal lymphoma, soft-tissue sarcoma, surgery. Abbreviations: BHCG, β-human chorionic gonadotropin; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CT,
computed tomography; FNAC, fine-needle aspiration cytology; GCSF, granulocyte colony stimulating factor; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; STS, soft-tissue sarcoma; USS, ultrasound imaging.
INTRODUCTION Benign soft-tissue masses are common whereas soft-tissue malignancies are rare.1,2 However, a variety of malignancies may result in a soft-tissue mass, each of which requires accurate identification because the treatment may differ widely depending on the precise diagnosis. The commonest malignant soft-tissue mass is a soft-tissue sarcoma (STS).3 Although the incidence of malignant lymphoma is up to 10 times commoner than STS and is increasing,3,4 the involvement of soft-tissue by lymphoma, either as a primary event or as part of more disseminated disease is rare.3–6 Thus, although painless lymphadenopathy is the initial abnormality in the majority of patients with malignant lymphoma, a rare subgroup may present with an isolated soft-tissue mass either in an extremity, the trunk or as a large retro-peritoneal mass mimicking the more common STS.2,5,7 These lymphomas presenting and mimicking soft-tissue masses are important to the surgeon because their management differs to that of other malignant and non-neoplastic soft-tissue masses,1 where the usual treatment is excisional surgery. In contrast, lymphoma is best treated by chemotherapy and/or radiotherapy rather than major resectional surgery.
B. Knowles MB BS; J. W. Serpell MD, FRACS. Correspondence: Associate Professor J. W. Serpell, 29 Hastings Road, Frankston, Vic. 3199, Australia. Email:
[email protected] Accepted for publication 18 September 2002.
Nearly all previously reported cases of lymphomas presenting as soft-tissue masses are in the pathology literature.1,4–6,8,9 Few of these reports define the typical clinical, radiological and diagnostic features of this condition. The aims of the present study were therefore to (i) report the clinical and radiological features, methods of diagnosis, treatment and clinical outcome of a series of patients who presented with lymphomas mimicking soft-tissue sarcomas; (ii) identify factors suggesting the diagnosis; and (iii) emphasize the important aspects of their management.
METHODS A retrospective review of the senior author’s (JWS) soft-tissue database (165 tumours collected between 1991 and 2002) was undertaken to identify patients referred with a suspected diagnosis of soft-tissue tumour and subsequently shown to have lymphoma. In addition, the database of a previous 12-month (1989/ 1990) series of 130 soft-tissue tumours referred for investigation to the Royal Marsden Hospital in London was also reviewed for patients with lymphoma.1 Masses developing within common extremity lymph node sites, including cervical, axillary, and inguinal nodes were excluded. All masses presenting as soft-tissue tumours thought not to be arising from these lymph node sites were included. Therefore two patients with supraclavicular masses, clinically diagnosed as lipomas were included as a subgroup, although they were subsequently shown to be masses due to underlying supraclavicular nodal lymphoma. Two other patients with soft-tissue neck masses clinically presenting as STS were included; one
71F
43F
67M
41M
70F
63M
90F
47F
36F
61F
78F
76F
46F
M F F M
1
2
3
4
5
6
7
8
9
10
11
12
13
14m 15m 16m 17m
(L) Forearm
Site
Peri-aortic and intra-mesenteric Small bowel mesentry
CT-guided core biopsy CT-guided FNA + core biopsy
CT-guided FNA + core biopsy
FNA+ incisional biopsy
Method of diagnosis
(R) sided neck mass, ? (R) lobe of thyroid
(L) Supra-clavicular Fossa FNA + incisional biopsy (R) Shoulder (R) Buttock (R) Anterior chest wall (L) Shoulder
Painless increasing STM 5 × 3 × 3 cm
Painless STM Painless STM Painless STM Painless STM
(L) Forearm swelling 15 × 7 cm and weakness Painless increasing STM 15 × 15 cm
USS-guided FNA + core biopsy + incisional biopsy (L) forearm – extensor USS-guided core compartment into flexor biopsy Retro-peritoneal CT-guided core biopsy
Clinical course
DLC Stage IEA Intermediate Grade
CHOP + Local Clinical remission at 2 years radiotherapy
Disease free at 3 years
CHOP + Local Clinical remission radiotherapy CHOP + Local Clinical remission for 3 years before radiotherapy high grade transformation to DLC held in partial remission by second round to high dose chemotherapy FMC Staging to be CHOP + Local Yet to undergo therapy completed low grade radiotherapy
DLC State IEA Intermediate grade FSC Stage IVA Low grade
DLC in NLP HD Stage IA
CHOP
Emergency Clinical remission at 18 months CHOP + Local radiotherapy CHOP + Local Clinical remission radiotherapy
CHOP + Local Represented transformation to DLC. radiotherapy Poor response to current chemoand radiotherapy
DLC Stage IVA Intermediate grade
DLC Stage IA Intermediate grade
Good response to first cycle of CHOP CHOP Relapse after 5 months responded to high dose chemotherapy, but recurred again 3 months later. High dose CXRT with GSF rescue CHOP + Local Undergoing initial therapy radiotherapy
CHOP
CHOP + Local Clinical remission at 4 years later radiotherapy
Local No evidence of disease 1 year later radiotherapy
Initial therapy
SLL Stage IIA Low grade DLC Stage IEA Intermediate grade
SLL Stage IIA Intermediate grade
NLP HD Stage IEA
Pathology/stage
USS-guided FNA NS HD Stage IIEA + core biopsy + incisional biopsy USS-guided core MC HD Stage IVA biopsy
FNA + core biopsy
Painless increasing STM 5 × 6 × 6 cm
(L) paravertebral mass extending into psoas and erector spine (L) Supra-clavicular fossa
2.5 × 2 × 1.5 cm Mid (L) sided neck mass outside thyroid
6 × 4 cm
Encasing (L) iliac wing CT-guided core with infiltration of the biopsy abdominal wall muscle 10 × 6.5 × 4 cm (L) Adductor region thigh USS-guided FNA + core biopsy
12 × 5 cm
7 × 5.5 × 8 cm
Large diffuse
12 cm diameter Peri-aortic abdominal
10 × 10 mm
Size
Painless increasing STM 7 × 2 cm
Incidental mass seen on MRI
Previous low grade FLC in remission 10 months presents with increasing STM Neck mass, airway obstruction
Swollen (L) leg with painless pelvic mass
Epigastric pain with mobile mass
Pain between scapula and LUQ abdominal mass 2/12 Bilateral leg swelling
Painless STM Past history of NLP HD
Presentation
MC HD, mixed cellularity Hodgkin’s disease; NLP HD, nodular lymphocyte predominant Hodgkin’s disease; NS HD, nodular sclerosing Hodgkin’s disease; DLC, diffuse large-cell lymphoma; FLC, follicular large-cell lymphoma; FMC, follicular mixed-cell lymphoma; FSC, follicular small-cell; SLL, small lymphocytic lymphoma; STM, soft-tissue mass; FNA, fine-needle aspiration; CT, computed tomography; USS, ultrasound imaging; all staging: Ann Arbour system; CHOP, cyclophosphamide, vincristine, adriamycin, and prednisolone.
Age/sex
Case
Table 1. Patient series characteristics
LYMPHOMA MIMICKING SOFT-TISSUE SARCOMA 27
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KNOWLES AND SERPELL
mass was subsequently shown to be lymphoma of the thyroid, and the other mass was shown to be nodal lymphoma in the middeep cervical chain. For each patient clinical features, primary tumour characteristics, site, size, method of diagnosis, radiological findings, and treatment were recorded. The patients were classified according to the Ann Arbour Staging Classification for nonHodgkin’s malignant lymphoma and subclassified by histological types. Details of clinical follow up were obtained by review of the patient’s history and communication with the patient’s oncologist.
RESULTS Thirteen cases of lymphoma mimicking soft-tissue tumours were identified. These came from the database of 165 tumours. A further four cases were identified from the Royal Marsden Hospital database of 130 cases referred during a 12-month period in 1989/1990.1 Limited information was available for these four cases but data on sex, site, and method of diagnosis were available and are included in these analyses of results. All other results presented are based on complete data for the 13 patients of the senior authors’ series. The features of the 17 patients are summarized in Table 1. The patients were of mean age 60.7 ± 16.7 years (range: 32–90 years). There were 12 women and five men. All patients presented with an enlarging soft-tissue mass or with complications due to the mass. One patient presented with airway obstruction. Two patients presented with ipsilateral limb oedema. One patient presented due to an incidental finding on a magnetic resonance imaging (MRI) scan for a different indication. No patient complained of B symptoms such as weight loss, night sweats, unexplained fevers, rash or arthralgia. The mean size of the mass was 9.0 cm ± 4.0 cm (range: 2.5–15 cm) in the largest dimension, as measured on computed tomography (CT) or ultrasound imaging (USS). The most common radiological investigation was CT scan. Eleven of the 13 cases for whom data were available had CT imaging demonstrating diffuse tumour with an attenuation lower than that of normal Table 2. Method of tissue diagnosis used Investigation
n
Core biopsy only FNA + core biopsy FNA + incisional biopsy FNA + incisional + core biopsy
9 4 2 2
Total
17
FNA, fine-needle aspiration.
Table 3. Sensitivity in diagnosis Investigation
n
True positive
False negative
Sensitivity (%)
FNA Core biopsy Incisional
8 15 4
5 14 4
3 1 0
62.5 93.3 100
A positive result indicates that features of a lymphoma were detected. Further studies may have been required to completely type the disease. FNA, fine-needle aspiration.
muscle. In addition seven (54%) of 13 (cases 2, 3, 8, 9, 10, 12 and 13) demonstrated local lymphadenopathy. Cases 5, 9 and 11 had a mass crossing major soft-tissue boundary planes as follows: attachments to the wing of the ilium; the thoraco-lumbar fascia; and interosseous membrane, respectively. Six (46%) of 13 (cases 2, 3, 4, 6, 11 and 12) demonstrated encasement of vascular structures on CT scanning. The two cases not imaged with CT were investigated with MRI. Final diagnosis, including lymphoma subtyping and grading in the 17 patients was established by core biopsy in 13 patients, and incisional biopsy in four patients (Table 2). Fine-needle aspiration cytology (FNAC) diagnosed lymphoma in five of eight (a sensitivity of 62.5%), but further tissue was required for lymphoma typing in each of these cases. Overall 15 patients underwent core biopsy, which was positive for lymphoma in 14 patients. The overall sensitivity of core biopsy was 93% (Table 3). Four cases required an incisional biopsy. All incisional biopsies were performed after initial investigation with either FNAC (n = 3) and/or core biopsy (n = 1) proved inconclusive for malignancy or it was thought that further tissue was required for subtyping of the lymphoma. Each incisional biopsy enabled a final tissue diagnosis to be made with no further tissue sampling required. Overall, six patients had stage I disease (the single and only site of involvement). Three patients had stage II disease (involvement of two or more regions on the same side of the diaphragm). Three patients had widely disseminated stage IV disease. One patient is yet to be completely staged. Seven of the patients had extra-nodal involvement as the presenting mass and five of these patients were classified as having primary stage 1E soft-tissue lymphomas. The remaining six patients had nodal tissue origins, but presenting as extra-nodal soft-tissue masses. The histological subtypes of the lymphomas were varied. Ten patients had non-Hodgkin’s lymphomas, including one patient with a diffuse, large-cell non-Hodgkin’s lymphoma arising with a nodular predominant Hodgkin’s disease. Three patients had Hodgkin’s disease. Of the non-Hodgkin’s patients, in six the subtype was diffuse large-cell lymphoma, two had small lymphocytic cell lymphoma and one each had follicular small-cell and follicular mixed-cell lymphoma. Seven of these 10 cases of non-Hodgkin’s lymphoma were intermediate grade, and three were low grade. Chemotherapy was given to 12 patients; of these, eight patients were given adjuvant radiotherapy and one patient received radiotherapy alone. Of the 13 patients in the present series, all are alive with a mean follow up of 19 months (range: 1–48 months). Seven patients are in clinical remission and four are currently undergoing initial therapy. Of the remaining two cases, case 4 had disease relapse after 5 months of clinical remission that responded to high-dose chemotherapy. This patient has undergone further high-dose chemotherapy with granulocyte colony stimulating factor (GCSF) rescue. Case 12 had 3 years of clinical remission before high-grade transformation to a diffuse large-cell lymphoma that is being held in partial remission with chemotherapy.
DISCUSSION The present series of 17 patients has highlighted a rare subgroup of patients with lymphoma mimicking the presentation of STS. When a patient presents with a clinically malignant soft-tissue mass, the differential diagnosis will include not only all varieties
LYMPHOMA MIMICKING SOFT-TISSUE SARCOMA
of benign masses but also a variety of malignant tumours involving soft tissue including; soft-tissue sarcomas, metastatic melanoma, metastatic carcinoma (e.g. small-cell carcinoma of the lung), malignant bone tumours involving soft tissue (e.g. Ewing’s sarcoma), and lymphomas.1 Distinction between these by accurate diagnosis is essential because treatments will often differ significantly. For example, STS will usually be treated by a radical local excision of the tumour, perhaps sacrificing some degree of function to achieve tumour clearance, even in the context of limb conservation. For metastatic lung cancer, chemotherapy may be appropriate. For lymphoma, radical surgery of excisional type is neither appropriate nor definitive and the usual treatment of choice will involve chemotherapy and/or radiotherapy. The commonest malignant soft-tissue mass is a soft-tissue sarcoma,3 with an incidence of 1.5 per 100 000 population in the USA.2 However, as a group, STS represent less than 1% of all malignant tumours.1 Most STS present as a painless increasing soft-tissue mass.2 Lymphomas presenting as a soft-tissue mass in the extremity are even rarer. A review of all malignant lymphomas seen at the Mayo Clinic from 1976 to 1986 found eight cases of stage IA extra-nodal malignant lymphoma among 7000 cases. These cases therefore represent only 0.11% of all malignant lymphomas.4 It is not surprising therefore that in the majority of cases the appearance of a discrete soft-tissue mass in an otherwise healthy patient is interpreted to represent either a benign softtissue tumour such as a lipoma or a soft-tissue sarcoma. It should be remembered that tumours deep to the deep fascia are more likely to be malignant than benign.10 The gastrointestinal tract, orbit, respiratory tract, skin, bone, thyroid, and the central nervous system are more common sites of extra-nodal lymphoma than soft tissues. Extra-nodal lymphoma can occur as a primary (stage IE) process or as a manifestation of disseminated disease. Primary extra-nodal soft-tissue lymphoma is by definition a tumour of the soft tissues in a region not typically considered to be rich in lymph nodes. The commonest sites for STS and extra-nodal lymphomas are the lower limb, especially in the thigh (25%), followed by retroperitoneum (16%), then the upper limb (11%).2,5 However, a number of patients in the present series of lymphomas presented with masses in unusual sites such as the erector spinae muscle, the supraclavicular fossa, and surrounding the wing of the ilium. Therefore, although STS may occur in any site, the presence of a malignant soft-tissue tumour in an unusual position should raise a clinical suspicion of lymphoma. Of the 17 cases of lymphoma presenting as mimics of STS, nine patients presented with a soft-tissue mass of the extremity or parietal trunk, and these were most easily confused with a STS. Four patients presented with retroperitoneal masses without ‘B symptoms’ or clinical lymphadenopathy. Two patients presented with apparent lipomas of the supraclavicular fossa. Both were subsequently shown to have underlying lymphoma of lymph nodes, presumably pushing the supraclavicular fat pad into prominence and thereby mimicking a lipoma. The cases of these patients emphasize the importance of achieving at least a cytological diagnosis for ‘lipomas’ that are growing, that have appeared recently, that are clinically firmer than usual, that are deep to the deep fascia, or greater than 5 cm in maximal dimension. Lipomas have specific diagnostic appearances on CT scanning, and hence should be imaged if there is concern about their diagnosis. The most common cause of a large retroperitoneal mass is STS (45%), followed by urogenital and lymphomatous malignancies
29
(18% each), and then benign causes (18%).7 In these patients with retroperitoneal masses thorough preoperative assessment is essential to ensure appropriate treatment. A soft-tissue sarcoma will require resection if possible, whereas a germ cell urogenital secondary tumour will be treated by specific chemotherapy, which will differ in turn to that required for lymphoma. Such a distinction of these retroperitoneal masses is usually possible with core biopsy, immunohistochemistry and tumour markers such as lactate dehydrogenase (LDH), α-fetoprotein, β-human chorionic gonadotropin (BHCG), carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125 and CA 19. Regional lymph node involvement is seen infrequently in adult STS (4% of all patients), except in some cases of synovial and epitheloid sarcomas, and indicates poor prognosis.2,11,12 Therefore a mass with associated lymphadenopathy, whether detected clinically or on CT scanning, should raise suspicion of a diagnosis other than STS, for example lymphoma. Preoperative imaging is essential to plan the biopsy and definitive resection of soft-tissue tumours. The majority of the present patients had their tumours imaged with CT. The specific features of CT scanning suggesting a diagnosis of lymphoma rather than STS have not previously been addressed.13 However, it has previously been reported that radiological evidence of confluent lymphadenopathy encasing a major vascular structure favours the diagnosis of lymphoma over STS.2 Six of our 13 cases demonstrated this finding. Seven (54%) of our 13 cases had lymph node involvement on CT, suggesting a diagnosis other than STS. We also noted three cases in which CT demonstrated a soft-tissue mass invading normal fascial planes including the interosseous membrane, the thoraco-lumbar fascia and the attachments to the wing of the ilium. Grem et al. reported similar fascial plane invasion in their three-patient case series.14 Except in advanced cases or in tumours disrupted by previous surgical intervention, most STS respect fascial borders and during continued growth tend to spread along fascial boundaries, vessels and nerves rather than invading across these barriers. Hence, they may remain within well-defined anatomical compartments.15 Therefore, we suggest that the demonstration on CT or MRI of a soft-tissue mass crossing fascial planes is a pointer to the diagnosis of a soft-tissue lymphoma. It is, however, recognized that clinical and radiological studies cannot reliably distinguish soft-tissue lymphoma from soft-tissue sarcoma, rather this distinction requires pathological examination of tumour tissue. Accurate diagnosis, usually achievable by core biopsy, should be the aim preoperatively. Core biopsy is known to be highly accurate, with overall accuracy rates reported between 94% and 100%.1,16–19 This high degree of accuracy is confirmed in the current series with a sensitivity for diagnosis of lymphoma of 93%. Core biopsy allows definitive one-stage surgery for patients with STS, appropriate planning of multidisciplinary treatment preoperatively, and has the advantage of the opportunity for appropriate preoperative counselling of the patient. In addition, core biopsy will avoid unnecessary open biopsies, which have the attendant possible complications of wound infection and breakdown in a significant percentage of cases.1,20 In the present series it has been shown that lymphomas mimicking an STS can be diagnosed by core biopsy, thereby avoiding inappropriate radical operation and allowing appropriate staging and therapy. In most cases the tissue obtained by core biopsy is adequate to subtype the tumour. However, a core biopsy should be a carefully planned procedure involving surgeon, radiologist and pathologist to ensure appropriate siting of the biopsy, handling of the tissue and
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KNOWLES AND SERPELL
that an adequate amount of tissue is obtained so that all studies including immunohistochemistry can be performed. In the present series, and in the experience of others, although lymphomas can be diagnosed on cytology and distinguished from other malignancies involving soft tissue, they cannot be subtyped.19 Hence, a further biopsy following FNAC will be required for patients with lymphoma. Avoidance of inappropriate radical surgery for a patient with lymphoma will not only avoid potential postoperative morbidity but, because the tumour is left in situ it will provide a useful clinical parameter to assess effectiveness and response to treatment. In the present series there was one false negative core biopsy due to a mixed lipoma and lymphoma that developed within the supraclavicular fossa. This patient therefore required an incisional biopsy in addition to cytology and core biopsy. We suggest, as have others, that the likelihood of core biopsy providing a definitive diagnosis is increased if undertaken under ultrasound control to ensure the sampling of solid and non-necrotic elements of the tumour.21 In conclusion the present series has demonstrated an important subgroup of patients who presented with lymphoma mimicking a soft-tissue sarcoma. The diagnosis is important because radical excisional surgery is inappropriate and treatment with chemotherapy and/or radiotherapy is effective. The diagnosis may be suggested by clinical features and also by CT scan findings indicating invasion of fascial planes not normally breached by softtissue sarcomas, the presence of occult lymphadenopathy, and confluent lymphadenopathy encasing major vascular structures. Core biopsy is accurate in diagnosing these soft-tissue lymphomas and allows full subtyping. The possibility of a soft-tissue lymphoma should always be part of the differential diagnosis of a presumed soft-tissue sarcoma.
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5. Lanham G, Weiss S, Enzinger F. Malignant lymphoma: A study of 75 cases presenting in soft tissue. Am. J. Surg. Pathol. 1989; 13: 1–10. 6. Wakely P, Frable W, Kneisl J. Soft tissue aspiration cytopathology of malignant lymphoma and leukemia. Cancer 2001; 93: 35–9. 7. Storm F, Mahvi D. Diagnosis and management of retroperitoneal soft tissue sarcoma. Ann. Surg. 1990; 214: 2–10. 8. Axiotics C, Fuks J, Jennings T, Kadish A. Peripheral t-cell lymphoma presenting as a soft tissue mass of the extremity. Arch. Pathol. Lab. Med. 1988; 112: 850–1. 9. Radhi J, Ibrahiem J, Al-Tweigeri T. Soft tissue malignant lymphoma at sites of previous surgery. J. Clin. Pathol. 1998; 51: 629–32. 10. Shiu MH, Hajdu SI. Management of soft tissue sarcomas of the extremity. Semin. Oncol. 1981; 8: 172–9. 11. Westbury G. Surgery in the management of soft tissue sarcoma. Clin. Oncol. 1989; 1: 101–5. 12. Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults: Analysis of data from a prospective data base of 1,772 sarcoma patients. Ann. Surg. 1993; 217: 72–7. 13. Malloy P, Fishman E, Magid D. Lymphoma of bone, muscle, and skin: CT findings. AJR 1992; 159: 805–9. 14. Grem J, Neville A, Smith S, Gould H, Love R, Trump D. Massive skeletal muscle invasion by lymphoma. Arch. Intern. Med. 1985; 145: 1818–21. 15. Peabody T, Simon M. Principles of staging of soft tissue sarcomas. Clin. Orthop. 1993; 289: 19–31. 16. Ball ABS, Fisher C, Pittman M, Watkins RM, Westbury G. Diagnosis of soft tissue tumours by Tru-cut biopsy. Br. J. Surg. 1990; 77: 756–8. 17. Kissin MW, Fisher C, Carter RL, Horton LWL, Westbury G. Value of Tru-cut biopsy in the diagnosis of soft tissue sarcomas. Br. J. Surg. 1986; 73: 742–4. 18. Serpell JW, Pitcher ME. Pre-operative core biopsy of soft-tissue tumours facilitates their surgical management. Aust. N.Z. J. Surg. 1998; 68: 345–9. 19. Barth RJ, Merino MJ, Solomon D, Yang JC, Baker AR. A prospective study of the value of core needle biopsy and fine needle aspiration in the diagnosis of soft tissue masses. Surgery 1992; 112: 536–43. 20. Mankin HJ, Lange TA, Spanier SS. The hazards of biopsy in patients with malignant primary bone and soft tissue sarcomas. J. Bone Joint Surg. Am. 1982; 64: 1121–7. 21. Ayala AG, Ro JY, Fanning CV, Flores JP, Yasko AW. Core needle biopsy and fine needle aspiration in the diagnosis of bone and soft tissue lesions. Hematol. Oncol. Clin. North Am. 1995; 9: 633–51.
