PHYLLODES TUMOURS: A CLINICOPATHOLOGICAL REVIEW OF 30 CASES

Thirty cases of phyllodes tumour (cystosarcoma phyllodes) of the breast that presented to the Clinical Oncology Unit at Guy's Hospital were reviewed. Tumours were classified as benign, malignant or borderline according to the following histological criteria: mitotic rate, nuclear pleomorphism, stromal overgrowth and tumour margins. In 14 (46.5%) cases the tumours were considered histologically benign, in 11 (36.5%) malignant, and in five (17%) borderline. Recurrence was seen in a similar proportion of patients with tumours classified as benign (21 %) and malignant (18 %) according to histological criteria. Malignant lesions tended to recur earlier. Infiltrating tumour margins were noted in all patients and stromal overgrowth in all hut one in whom recurrence was observed. Risk of recurrence also appeared to he related to tumour size. Only one patient developed distant metastases and died of her disease. Because of treatment variation no conclusion can he made regarding optimal therapy but the importance of adequate clearance, either through wide excision or mastectomy, is emphasized for all phyllodes tumours irrespective of histological features.     

Beta irradiation of recurrent ptergia: results and complications.

Although postoperative beta irradiation for prevention of pterygium recurrence is widely used, its complication rate has not been widely appreciated. Thirty-six patients underwent pterygium excision followed by irradiation with 90Sr to between 1600 and 5300 cGy (median 2400) in two to four fractions over 7 to 27 days. A median of three fields were used in each treatment course (range two to 10). Most patients had undergone previous treatment for their pterygia, including surgery alone (25 patients), or both surgery and irradiation (5 patients). Overall, recurrences developed in 10 eyes (28%). Recurrence occurred in one eye after re-irradiation (20%), compared to 9 of 31 (29%) previously non-irradiated eyes (p greater than 0.1). There was no association with number of excisions and recurrences, although all but 6 patients had undergone more than one excision. Thirteen patients (36%) developed complications including: epithelial defect or corneal thinning (3), symblepharon (5), cataract (4) and corneal ulceration (1). Complications developed in 4 of the 5 (80%) re-irradiated eyes compared to 9 of 31 (29%) previously non-irradiated eyes (p less than 0.05). The power of the statistical analysis was limited by sample size, but no significant association was observed between the development of complications or recurrences and total dose, number of abutting fields, number of previous surgical excisions or patient age, even when re-irradiated patients were excluded. Recently described calibration uncertainties with the 90Sr applicator may explain in part these complications. Alternatively, technical factors such as the number of fields or volume treated may play a role. Excessive complications and recurrences with the use of postoperative beta irradiation in this series emphasize the danger of re-treatment and the need for alternative safe and effective therapies.     

Transperineal percutaneous iridium-192 interstitial template implant of the prostate: results and complications in 321 patients.

A total of 321 patients with localized adenocarcinoma of the prostate treated by modified pelvic lymphadenectomy, Iridium-192 implant, and external beam iridium radiation were retrospectively reviewed. Analysis covered 8 years between 1981 and 1989 with a median population age of 72 (range 42 through 82 years). Disease-free survival for the entire group is 69% at 5 years with a median follow-up of 34 months (range 1.5 months to 98.5 months). As expected, both bulkier disease and positive nodal status adversely affected 5-year disease-free survival (p = 0.0001 for both). For tumors stage T1b (A2), T2a (B1), T2b (B2), T3 (C) the disease-free survival is 89.5%, 89.9%, 64.7%, and 48.8%, respectively; for NO disease 5-year disease-free survival is 76.5% versus N1/N2 disease with 5-year disease-free survival of 33.2%. Local control was excellent except for bulkier disease (p = 0.009). Tumors T1b, T2a, T2b, and T3 have 60-month local control rates of 95%, 93%, 83.6%, and 73.1%, respectively. Histologic grade also affected disease-free survival and local control with grade 1, grade 2, grade 3 showing 81.2%, 65.7%, and 45.1% disease-free survival at 5 years; and 93.6%, 82.2%, and 72.4% local control at 5 years. Estimates obtained using Kaplan-Meier method. Radiation induced morbidity was analyzed separately for all patients, there were 41 patients (13% of total) with 54 documented complications. There were no Grade 4 or 5 complications as per RTOG categories. Only 3 cases showed grade 3 complications (1%) and 51 cases showed grade 2 complications (15.9%). Grade 1 complications were not recorded. Of the grade 2 and grade 3 complications 30 were GU and 22 were rectal. The morbidity associated with combined interstitial implantation by transperineal percutaneous template and external beam iridium radiation for the localized prostate cancer is minimal with excellent local control and disease-free survival.     

Monoclonal antibodies directed characterization of epidermal and hepatic cytochrome P-450 isozymes induced by skin application of therapeutic crude coal tar

A single application of crude coal tar (CCT) solution (USP) to the skin of neonatal rats was shown to induce epidermal and hepatic cytochrome P-450(P-450)-dependent monooxygenase activities. To further characterize the induction response, in this study we have utilized highly specific monoclonal antibodies (MoAb) 1-7-1, 2-66-3, and 1-98-1 directed against highly purified rat liver P-450s induced by 3-methyl-cholanthrene, phenobarbital and ethanol, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of hepatic microsomes prepared from CCT-treated animals showed a significant increase in the coomassie blue stainable proteins in the P-450 region; however, this was not evident in epidermal microsomes. Immunoblot analysis of epidermal and hepatic microsomes with MoAb 1-7-1 revealed strong immunoprecipitin bands in both tissues. MoAb 2-66-3 showed significant immunoreactivity only with hepatic microsomes. Interestingly, CCT treatment resulted in suppression of immunoreactivity with MoAb 1-98-1 in hepatic microsomes. MoAb 1-7-1 and 2-66-3 exhibited concentration-dependent inhibitory effects in aryl hydrocarbon hydroxylase and 7-ethoxycoumarin-O-deethylase activities induced by CCT application. MoAb 1-7-1 was substantially more effective in this respect. Epidermal and hepatic microsomes prepared from CCT-treated rats showed significantly greater metabolism of benzo(a)pyrene (BP). MoAb 1-7-1 and MoAb 2-66-3 inhibited BP metabolism in both the tissues. However, MoAb 1-7-1 was more inhibitory in this regard as compared to MoAb 2-66-3. These studies indicate that topical application of therapeutic CCT to the skin of neonatal rats results in induction of P-450 isozyme c in epidermis and isozymes b and c in liver, and that this induction is associated with the suppression of P-450 isozyme j in liver.     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.