Diagnosis and management of primary breast sarcoma

Primary sarcoma of the breast is an extremely rare and heterogeneous disease. The rarity of this tumour limits most studies to small retrospective case reviews and case reports and has made clinicopathological study difficult. This article reviews the current literature on the diagnosis and management of breast sarcoma. The optimal treatment of breast sarcoma involves a multidisciplinary team prior to the initiation of treatment. Patients with tumours less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Negative surgical margins are more important for local recurrence and overall survival than the extent of surgical resection. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumour and help obtain negative surgical margins. Whether chemotherapy is indicated is primarily determined by tumour size. There is evidence that tumours larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis. After surgical resection, patients with chemosensitive tumours should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Radiation therapy should be used to improve local control in cases in which the tumour is larger than 5 cm and in cases with positive surgical margins. We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. The appropriate treatment of breast sarcoma requires a multidisciplinary team approach necessitating experienced sarcoma surgeons, pathologists, radiotherapists and medical oncologists. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival.     

Is chemosensitivity testing for peri-operative treatment planning in gastro-intestinal cancer by the human tumour colony assay worthwhile?

Based on the concept of a combined modality cancer treatment in surgical oncology, the use of the human tumour colony assay for routine chemosensitivity testing and prospective treatment planning was investigated in 204 surgical biopsies of primary human solid tumours. The majority of the tumours (135/204) were of gastro-intestinal (GI) origin. Sufficient growth for drug testing occurred in 29-67% of all tumours depending on the tumour type, with a mean of 36% in GI-carcinomas. Chemosensitivity testing in vitro against standard anti-cancer agents correlated well with clinical experience, 5-FU and FUDR being the most active drugs (27% respectively 24% sensitive tumours in vitro) in GI-carcinomas. Relatively good agreement of in vitro/in vivo correlations was seen with an overall of 25/32 correct predictions in GI and other tumours. Predictivity was particularly good for loco-regional chemotherapy. Nevertheless, the limited in vitro growth rate of gastro-intestinal tumour specimens and their chemoresistance restrict the use of this method-in particular with respect to individual treatment planning.     

Cerebral haemangiopericytoma treated with conservative surgery and radiotherapy

Cerebral haemangiopericytomas are rare tumours that resemble meningiomas but behave more aggressively, with a tendency to metastasize. We report two patients with haemangiopericytoma who had limited surgical resections owing to perioperative blood loss but who had massive tumour shrinkage after a course of radical radiotherapy. We suggest a more conservative surgical approach to the management of these tumours.     

Proliferative response of human and animal tumours to surgical wounding of normal tissues: onset, duration and inhibition.

Acceleration of secondary tumour growth and metastases following excision of a primary tumour has been attributed to the consequent removal of primary tumour-generated inhibitory factors. However, our studies have shown that surgical wounding of normal tissues significantly stimulated the growth of malignant tissues without the concomitant presence or excision of a tumour mass. A humoral stimulating component was indicated by the proliferative response of tumours and metastases distant from the surgical wound. All 16 human and murine tumours, of nine different histologies, showed a measurable acceleration of growth when implanted in surgically treated animals, suggesting that the ability of malignant tissue to respond to surgical wounding of normal tissue was not histologically or species specific. The proliferative surge of malignant tissues was detectable soon after wounding and had a duration of 2-3 days. The surgical wound as the source of the tumour-stimulating factor(s) was affirmed by the significant inhibition of tumour proliferative responses when a somatostatin analogue was applied topically to the surgical wound within 1 h of wounding, and/or during the critical tumour-stimulatory period of 1-2 days after wounding. A potential therapeutic window for reducing a risk factor that may be inadvertently imposed upon every surgical/oncology patient is indicated.     

Immune responses to naturally occurring rat sarcomas.

Attempts were made to induce immunity to 5 spontaneous rat sarcomas transplanted into syngeneic recipients. Rats were immunized by surgical removal of growing tumour transplants or by treatment with attenuated tumour, followed by challenge with tumour cells in suspension. Two tumours wee apparently not immunogenic, but a low level of immunity was induced against 2, and weak evidence of immunity was observed with another. Induced immunity was individually specific rather than cross-reactive. It is concluded that, contrary to some reports, some spontaneous animal tumours are immunogenic in the strain of origin.     

Peripheral plasma immunoreactive 6-oxo-prostaglandin F1 alpha and gynaecological tumours.

Peripheral plasma levels of immunoreactive 6-oxo-PGF1 alpha, the stable hydrolysis product of prostacyclin, were significantly higher in female patients with tumours of the genital tract than in normal controls. In the groups with malignant tumours, these high levels declined after operation and/or radiotherapy if the tumour responded to treatment. In patients who did not respond to treatment or with tumour recurrence, levels of plasma 6-oxo-PGF1 alpha remained high or even rose further. Benign gynaecological tumours were also associated with significantly raised plasma 6-oxo-PGF1 alpha levels, and these fell to normal levels immediately on surgical removal of the tumour. Possible reasons for these alterations are described. Further investigations are warranted to see whether serial measurements of plasma 6-oxo-PGF1 alpha could be used as a prognostic index for the clinical status of patients with gynaecological tumours.     

Microbiology and management of infected solid tumours

Infection has been recognized as one of the major obstacles to the successful management of patients with malignant tumours. Aerobic and anaerobic bacteria of endogenous source are a major cause of infections in the necrotic tumour, especially when they occur in proximity to a site where these bacteria reside as part of the normal flora. Although surgical removal or evacuation of the purulent fluid is preferred, this is not always feasible in a patient with a malignant tumour. Antimicrobial therapy against potential bacterial pathogens is often the sole therapy or is used along with surgical drainage or removal of the infected area. This review describes the microbiology and management of infection in necrotic tumours.     

Angiosarcoma of the scalp presenting in association with borderline malignant phyllodes tumour of the breast

Phyllodes tumours and angiosarcoma are both rare mesenchymal tumours. There are no reports of their coexistence in the literature except in families with germline p53 mutations. Here we report a case of an elderly woman who developed an extensive angiosarcoma of the scalp nearly 4 years after surgical removal of a borderline malignant phyllodes tumour of the breast. The scalp lesion was initially thought more likely to be a metastasis of her first rare tumour than a second equally rare primary tumour, but histologically this was not the case. The case and the literature are discussed.     

Is MRI more accurate than CT in estimating the real size of adrenal tumours?

BACKGROUND: The size of adrenal tumour plays an important role in the indications for surgical excision of non-functioning adrenal tumours and in selecting the best surgical approach. Computed tomography (CT) has been reported to underestimate the real size of adrenal lesions. The accuracy of magnetic resonance imaging (MRI) in predicting the true tumour size has not been previously investigated. The present retrospective study investigates the accuracy of MRI and CT in the pre-operative determination of true adrenal tumour size. METHODS: The medical records of 65 patients who underwent adrenalectomy for an adrenal mass were reviewed. The size of adrenal tumours as determined by pre-operative MRI and/or CT was compared with the "true" histopathological size. The impact of histological diagnosis on size estimation was also investigated. RESULTS: The median age at diagnosis was 42 years (range 1-82 years) and more patients were female (60%). Five patients had bilateral adrenalectomy, thus giving rise to 70 adrenal specimens. The histopathological size of adrenal tumours ranged from 0.9 to 26 cm with a mean of 5.96 cm and a median of 4.70 cm. For tumours larger than 3 cm, MRI significantly underestimated the real tumour size by 20% (P<0.001). CT also underestimated the size of such tumours by 18.1% (P<0.003). Adrenal phaeochromocytomas were consistently underestimated by both modalities. CONCLUSIONS: MRI and CT significantly underestimated the true size of adrenal tumours larger than 3 cm by 20% and 18%, respectively. Surgeons and endocrinologists should interpret the pre-operative size of adrenal lesions with caution. Copyright Harcourt Publishers Limited.     

Interleukin 2 (IL-2) therapy: potential advantages of locoregional versus systemic administration.

There has been an apparent discrepancy between the results obtained with IL-2 based immunotherapy in animal tumour models, including veterinary cancer patients, and human cancer patients. We argue that this is due to differences in the therapeutic regimens used to treat human and veterinary cancer patients. The main differences are systemic therapy and surgical removal of the primary tumour in case of human cancer patients, whereas these treatment modalities are not used in IL-2 treated veterinary cancer cases. We have developed a treatment protocol, in which IL-2 is applied locally, that has been successful against transplanted tumours as well as spontaneous tumours of varying origin and immunogenicity. In view of immunobiological considerations we conclude that local treatment of cancer with IL-2 makes more sense than systemic treatment, as usually applied in the clinic, and that surgical removal of tumours may be detrimental to successful IL-2 therapy.     

Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin.

The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated.     

DNA flow cytometry of hereditary and sporadic paragangliomas (glomus tumours)

Paragangliomas (glomus tumours) are benign, hypervascular tumours which in general are treated by surgical excision. The indication for treatment of these often slow-growing tumours needs additional criteria for predicting tumour progressiveness. For this reason the nuclear DNA content of 99 paragangliomas, 65 of them originating from patients with a positive family history, was analysed by flow cytometry. Unequivocal evidence of DNA aneuploidy was found in 37% of these clinically and histologically benign tumours, the average duration of follow up amounting to at least 10 years. The DNA index of the aneuploid tumours ranged from 0.90 to 2.03. No correlation was found between DNA ploidy and familiality or between DNA content and clinical criteria indicative of tumour progression, which means that DNA ploidy of these tumours cannot serve as a predictor for an expected growth pattern or familiality. DNA aneuploidy in hereditary and sporadic paragangliomas is not clinically related to malignancy, but indicates that these tumours are true neoplasias cytogenetically.     

Pathological factors in survival of lung tumours: local extent, size, and nodal involvement

The pathological features, particularly local extent, size, and nodal involvement, of 405 surgical specimens of human lung carcinomas were studied. A direct relationship was found between local extent and size of the tumour and between local extent and the incidence of lymph node metastasis, but not between tumour size and the incidence of lymph node metastasis. The survival rates in the 405 tumours were calculated with the actuarial method in relation to the 3 pathological factors: local extent, lymph node metastasis and tumour size showed a predictive value in prognosis of lung tumours. Their prognostic value, however, was much more meaningful when the three pathological factors were considered in relation to each other. As a matter of fact, the size of the tumour showed no predictive value when lymph node metastasis was present. On the ground of the mutual influence of the 3 factors in affecting prognosis a pathological stage-grouping of lung tumours has been suggested.     

Preoperative assessment of parapharyngeal tumour

Due to deep seated location and presence of vital structures, the tumours of the parapharyngeal space poses difficulty in its early diagnosis, histological nature and surgical extirpation. Modes of radiological assessment in pre-computed tomography (GT) scan era were sialography of the parotid gland to see whether the tumour is of salivary origin and angiography to note the vascularity of the tumour. Post CT scan era has changed the assessment protocol. In this article, the authors have tried to make a comparative evalua?tion between non-contrast GT, GT with systemic contrast and GT sialogram in 14 cases of parapharyngeal tumours. Angiography was done only when the tumours showed marked enhancement with systemic contrast. Subsequently, 13 patients underwent surgery for removal of the mass. Application of high-resolution GT helped in not only to see the extent of the tumour but also to pinpoint the probable histologic nature.     

Measurement of tumour size in case selection for breast cancer therapy by clinical assessment and ultrasound.

AIMS: Clinical assessment of tumour size is often used to choose between mastectomy and primary medical therapy. Clinical and imaging modalities may have varying levels of accuracy across the range of tumour sizes. The aim of this study was to compare the accuracy of clinical measurement and ultrasound in discriminating palpable tumours up to 3 cm vs those greater than 3 cm. METHODS: A prospective analysis of 111 consecutive patients with palpable breast cancer was performed. All women had clinical measurement by caliper and ultrasound assessment prior to any needle biopsy. Clinical measurement and ultrasound assessment of size were compared to pathological tumour size of the surgical specimen. RESULTS: Both clinical and ultrasound measurement underestimate the size of larger tumours. The overall accuracy of clinical assessment and ultrasound examination in correctly identifying a 30 mm cut off was 70.3 and 77.5%, respectively. Ultrasound was significantly more accurate at determining the size of tumours <30 mm (p=0.007) but there was no significant difference between both modalities in assessing tumours greater than 30 mm. CONCLUSIONS: Ultrasound assessment of breast cancer size is more accurate than clinical assessment for tumours less than 30 mm. As clinical examination is as accurate on ultrasound for tumours greater than 30 mm, clinical assessment of tumour size alone is adequate to select patients for primary medical therapy or mastectomy.     

Chondromyxoid fibroma of the skull base: differential diagnosis and radiotherapy: two case reports and a review of the literature

Chondromyxoid fibromas are uncommon tumours mostly arising in long bones of young males. Involvement of the skull base is extremely rare. We describe two new cases of base of the skull chondromyxoid fibromas. The tumours were incompletely excised and irradiated with protons because of the high risk of complications of another surgical procedure. The rationale for proton therapy was based on the intimate relations between the tumour and the organs at risk. Skull base chondromyxoid fibroma is a very rare, slowly growing benign tumour that can cause severe disabilities due to tumour compression of critical structures. Only surgical resection has been shown to be relatively effective. We report two cases of incompletely excised lesions treated by postoperative high-dose radiation including proton therapy with no active disease and complication. Our review of the literature allows us to conclude that histological diagnosis of lesions in this site is a trap for pathologists and that radiotherapy is not contraindicated.     

Studies on the antigenicity of radiation-induced murine osteosarcomata

The immunogenicities of 15 murine osteosarcomata induced with a bone seeking radioisotope (⁹⁰Sr) in normal and chimaeric CBA mice were studied. Attempts were made to induce tumour-specific immunity in syngeneic mice by treatment with x-irradiated (15,000 rad) tumour or surgical excision of developing subcutaneous tumour grafts. Resistance was evoked against 6 tumours and this was relatively weak. With the remaining tumours, no resistance against the immunizing tumour could be demonstrated, even though the transplantation tests were made highly sensitive by the use of inocula of as few as 2 × 10³ cells in pre-irradiated (400 rad) hosts. Sera from mice immunized against each of the tumours were tested against viable cells of the immunizing tumour by indirect immunofluorescence. In no instance did tumour antisera give a convincing reaction with tumour cells although alloantisera raised by hyperimmunization of H-2 identical and H-2 different donors with osteosarcomata consistently gave strongly positive reactions. The results are interpreted as illustrating the weak tumour specific antigenicity of radiation-induced murine osteosarcomata. The possibility that antigenic deficiency is a consequence of immunosurveillance in this tumour system is discussed.     

Major surgery in elderly head and neck cancer patients: immediate and long-term surgical results and complication rates

Background: Evaluation of immediate and long-term surgical results in major surgery for the head and neck tumours in elderly patients and identification of tumour and patient related factors that affect the incidence and severity of surgical and medical complications.Methods: Retrospective analysis of a series of 24 consecutive patients aged 70 and over with head and neck tumours undergoing extensive surgical resections with reconstruction with/without osseous and/or soft tissue transfer. Patients’ demographics and surgery and tumour related data were extracted from appropriate charts and recorded. Pre-existent comorbid conditions, immediate and long-term surgical and medical complications were analysed. Pre-existing comorbidities were graded and staged using the Comorbidity Data Collection Form. Postoperative surgical and medical complications were scored according to their severity.Results: Overall complication rate in present study was 63% and 54% of patients experienced clinically important surgical and/or medical complications. However, medium admission time remained at 16 days. Presence of advanced comorbidity, longer operative times and advanced stage of disease seemed to influence the development of surgical or medical complications.Conclusions: Major surgery for head and neck tumours is of great value even in elderly patients providing very good surgical results with acceptable complication rates. The choice of treatment modality should be based on all factors affecting the treatment outcomes. In particular, the presence of the co-existent underlying diseases should be assessed meticulously and in cases with clinically important comorbidities the surgical treatment stress should be reduced to minimum.     

'Tumour volume' as a predictor of survival after resection of non-small-cell lung cancer (NSCLC)

Many factors have been individually related to outcome in populations of non-small-cell lung cancer (NSCLC) patients. Factors responsible for the outcome of an individual after surgical resection are poorly understood. We have examined the importance of ''tumour volume'' in determining prognosis of patients following resection of NSCLC in a multivariate model. Cox''s proportional hazard analysis was used to determine the relative prognostic significance of stage, patient age, gender, tumour cell-type, nodal score and estimated ''tumour volume'' in 669 cases with NSCLC treated with surgical resection, of which 280 had died. All factors (except tumour cell-type, P = 0.33) were individually related to survival (P < 0.05). When examined together, survival time was significantly and independently related to ''tumour volume'' and stage (P < 0.001), and other factors ceased to be significant. In cases with stage I or II tumours, risk of death was found to increase significantly with increasing estimated ''tumour volume'' (23.8% relative increase in hazard to death per doubling of ''tumour volume'', 95% confidence interval 13.2-35.2%, P < 0.001 stage I; P < 0.006 stage II). In cases with stage IIIa tumours this factor alone was the significant prognostic variable. In conclusion, an estimate of ''tumour volume'' significantly improves prediction of prognosis for individual NSCLC patients with UICC stage I or II tumours.     

Chondrosarcoma nose and paranasal sinuses — A surgeon’s dilemma

Chondrosarcomas of Nose and Paranasal Sinuses are very rare tumours. In the world literature only 77 cases were reported. Being rare tumours, no individual or institution has authenticated datas about its biological behaviour and ideal treatment. This tumour, inspite of being very well encapsulated has got the tendency to recur at the primary site and away from primary site. We had the opportunity of treating 3 cases of Chondrosarcoma Nose and Paranasal Sinuses at our Centre. There was no difficulty in establishing diagnosis. Problem was in offering an effective treatment. Our experience is similar to those of other authors. This tumours require repeated surgical excision. Recurrence is the rule inspite of tumour clearance. Radio therapy has got no role to play in the treatment of Chondrosarcoma.