Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in GIST patients.

BACKGROUND: The expression of the insulin-like growth factor (IGF) system has never been studied in gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: We studied the immunohistochemical expression of IGF1 receptor (IGFR-I), IGF1 and IGF2 in 94 samples of GISTs. IGF1 and IGF2 expression was scored in three classes: negative (N), moderate (M) and strong (S), according to staining intensity and extent. RESULTS: IGFR-I was overexpressed in all cases. IGF1 and IGF2 expression was absent in 25 and 48 cases, moderate in 29 and 16 cases and strong in 40 and 30 cases, respectively. Strong IGF1 expression significantly correlated with higher mitotic index (P = 0.0001), larger (P = 0.01), higher risk (P = 0.0002), metastatic (P = 0.0001) and relapsed (P = 0.04) GISTs. Strong IGF2 expression correlated with higher mitotic index (P = 0.05) and higher risk GISTs (P = 0.001). The Kaplan-Meier analysis (N versus M versus S) showed a significant worsening of the disease-free survival (DFS) with the increase of IGF1 (P = 0.02) and IGF2 (P = 0.02) expression. In the subgroup of patients with operated high-risk GISTs, there was a better trend in DFS for patients affected by GISTs with negative IGF1 and IGF2. CONCLUSIONS: The expression of IGF1 and IGF2 seems to predict relapse in GIST patients.

KIT and PDGFRalpha mutations in 104 patients with gastrointestinal stromal tumors (GISTs): a population-based study.

BACKGROUND: The prognostic significance of KIT or platelet-derived growth factor receptor alpha (PDGFRalpha) mutations in gastrointestinal stromal tumors (GISTs) is still controversial. PATIENTS AND METHODS: In all, 104 patients were diagnosed with GISTs by KIT immunoreactivity; tumor DNA was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17 and in PDGFRalpha exons 12 and 18. Disease-free survival (DFS) was analyzed in 85 radically resected patients. RESULTS: KIT mutations occurred in exon 11 (69), in exon 9 (11) and in exon 17 (1). PDGFRalpha mutations were detected in exon 18 (10) and in exon 12 (3). Ten GISTs were wild type. Exon 11 mutations were as follows: deletions in 42 cases and point mutations in 20 cases and insertions and duplications, respectively, in 2 and 5 cases. A better trend in DFS was evident for duplicated and point-mutated exon 11 KIT GISTs. There was a significant association between PDGFRalpha mutations, gastric location and lower mitotic index. Moreover, PDGFRalpha-mutated GISTs seemed to have a better outcome. CONCLUSIONS: Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFRalpha-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior.

Inadequacy of ultrasonography for monitoring response to treatment of liver metastases.

PURPOSE: We prospectively evaluated the clinical efficacy of ultrasonography (US) in monitoring the effect of medical treatment in patients with liver metastases, by comparing serial US assessment with serial magnetic resonance imaging (MRI) evaluation and clinical outcome in a group of 41 patients with solid tumors. PATIENTS AND METHODS: Both examinations were performed in patients with metastatic liver disease at the start of a new treatment modality and monthly thereafter for 3 months; close monitoring was prolonged beyond the third month in cases in which there was disagreement between the two techniques and the clinical course was not conclusive. RESULTS: Planned follow-up was completed in 37 cases. There was limited concordance between the two examinations: in 21 cases only (56.8%), US and MRI gave concordant information on the evolution of hepatic metastases; in eight cases, both agreed on progression of disease (PD), in 11 cases on stable disease (SD), and in one case each on partial response (PR) and complete response (CR). In the remaining 16 cases (43.2%), there was disagreement between the two examinations. On the basis of subsequent clinical course, this discrepancy was shown to be due to US inadequacy in 13 cases and to MRI inadequacy in one case; in two cases, the clinical course was not conclusive. The most striking limits of US appeared to be twofold: (1) a progressive appearance, with chemotherapy, of a diffusely inhomogeneous structure of the liver, resulting in obscuration of focal lesions (and a subsequent judgement of CR) in cases in which lesions were, on the contrary, detected at MRI and usually confirmed by subsequent clinical course; and (2) false US-determined PD in cases in which lesions proven at baseline MRI were noted at US only after one to two courses of therapy. CONCLUSION: We conclude that US, which is known to be inaccurate for screening of liver metastases, is unreliable for the follow-up of metastatic liver disease; despite its wide availability, low cost, and noninvasiveness, critical therapeutic decisions should not be made based on the outcome of this test.

A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer.

From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy.

Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer.

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.

Teniposide as single drug therapy for elderly patients affected by small cell lung cancer.

From January 1987 to December 1990, 26/105 previously untreated patients affected by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since 19 of them were older than 70 years and 7 suffered from severe chronic diseases, received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5, every 3 weeks until disease progression. After a minimum of two courses, 24 patients were evaluable for response: 13 with limited disease (LD) and 11 with extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol violation). Response rate, by disease stage, was: in the 13 LD, 1 complete response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the 11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95% confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of response was 7 months (range 2-32). Median overall duration of survival was 9 months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of courses delivered, whereas no further important side-effects were recorded, excluding alopecia, which was common. Teniposide used alone appeared a safe and effective palliative treatment for poor-risk patients; the major limitation was the low CR rate.

A phase I study of paclitaxel and 5-fluorouracil in advanced gastric cancer.

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of paclitaxel and 5-Fluorouracil (5-FU) in advanced gastric cancer patients. The patients, refractory to the PELF regimen (5-FU, leucovorin, cisplatin, epidoxorubicin), received weekly 5-FU at the fixed dose of 500 mg/m2, and escalating doses of paclitaxel every 3 weeks with a starting dose of 150 mg/m2 given as in 3-h infusion. The dose was escalated by 25 mg/m2 every 3 patients. Fifteen patients entered the study. The upper paclitaxel dose (225 mg/m2) was given to 6 patients. Up to this dose, no severe toxicity (grade 3-4) was recorded. Apart from alopecia, grade 1-2 leukopenia occurred in 5 patients and grade 1-2 neurotoxicity in 2 patients. All patients were evaluable for response (at least 2 cycles): 2 patients achieved an objective response (200 and 225 mg/m2). In 6 patients, treatment resulted in notable relief from symptoms. Out-patient paclitaxel given over 3 h and 5-FU may be combined safely for the treatment of patients with advanced gastric cancer. The recommended doses for phase II study are paclitaxel 225 mg/m2 and 5-FU 500 mg/m2.

Loss of hMLH1 expression correlates with improved survival in stage III-IV ovarian cancer patients.

Pre-clinical data suggest a relationship between DNA MisMatch Repair (MMR) system failure, particularly the inactivation of genes hMLH1 and hMSH2, and resistance to drugs like cisplatin and carboplatin. We studied the correlation between loss of hMLH1 expression in tumour cells and clinical outcome in 38 patients with ovarian cancer, who underwent cisplatin-based chemotherapy. 19 patients (56%) showed loss of hMLH1 expression (Group A) while 15 patients (44%) showed normal hMLH1 expression (Group B). 4 patients were not evaluable for hMLH1 expression. The 2 groups of patients were similar for clinical characteristics, response to chemotherapy and time to progression. Group A patients showed a median survival of 55 months whereas Group B patients had a median survival of 12 months (P=0.014). Loss of hMLH1 expression was the only independent predictor of survival in the multivariate analysis. Our observations suggest a relationship between loss of hMLH1 and improved survival in advanced ovarian cancer.

The value of necropsy in oncology.

The effectiveness of diagnostic procedures in cancer patients was evaluated by comparing clinical with necropsy findings. Necropsy and clinical records of 102 patients were reviewed for primary site and histology of tumour, metastatic sites, presence of second neoplasms, associated non-neoplastic diseases, terminal illness and cause of death. Major discordances between clinical and postmortem findings were found in 34 (33%) cases: in 10 of these a correct clinical definition of site and histology of the primary tumour would have resulted in a change of management and prognosis; in 4 cases in which a major non-neoplastic pathology had been responsible for death, correct diagnosis might have resulted in prolongation of survival. Spread of disease was generally underestimated, even for metastases in clinically accessible organs. Even more disappointing were the clinical data related to terminal illness and cause of death (43% overall concordance).

Symptomatic, stage IV, non-small-cell lung cancer (NSCLC): response, toxicity, performance status change and symptom relief in patients treated with cisplatin, vinblastine and mitomycin-C.

In a series of 46 symptomatic patients with metastatic, stage IV, non-small-cell lung cancer (NSCLC), we used a three-drug combination with cisplatin (120 mg/m2), vinblastine (6 mg/m2) and mitomycin-C (6 mg/m2) (PVM), repeated every 3 weeks. After two courses, we observed that none of the patients had achieved a complete response; 33% (15/46) had partial response (95% confidence limits: 19.2-46.8); 39% (18/46), stable disease and 28% (13/46), progressive disease. Median response duration was 14.0 weeks (range, 4-36.7), median time to progression 22.4 weeks (range, 7-44.4), and median survival time 26.4 weeks (range, 1-103). WHO grade III-IV myelotoxicity occurred in 15.2% of the courses administered, affecting 39.5% of patients, and severe nephrotoxicity was observed in 9.3% of patients. No toxic death occurred. The post-treatment KPS score increased in 7 patients with partial response (47%), 4 with stable disease (22%) and 1 with progressive disease (8%), while it decreased in 3 patients with partial response (20%), 3 with stable disease (17%) and 10 with progressive disease (77%). In all, KPS increased in 12/46 cases (26%). However, no statistically significant difference was observed when the KPS score before and after treatment was compared in the total group of patients or when it was compared in the total group of patients or when it was compared in responders and in non-responders. After chemotherapy, there was complete disappearance of at least one symptom in 27.1% of cases and improvement in 27.1%. Overall, major symptom control occurred in 54.3% of cases, with a median palliation time lasting 10 weeks (range, 4-32). Patients with partial remission and stable disease achieved symptomatic palliation in 90% and 55.5% of cases, respectively. When we compared the palliation rate between responders and non-responders, a significant difference was noted (Chi-square test: P < 0.05). Although our schedule did not produce a higher objective response rate and the KPS score was not significantly improved, the symptom palliation appeared worthwhile considering the highly unfavourable prognosis of the patients investigated.

Aminoglutethimide in advanced breast cancer: plasma levels and clinical results after low and high doses.

Drug plasma levels, metabolism data and clinical results were evaluated after the daily administration of either 500 or 1,000 mg aminoglutethimide (AG, Orimeten, Ciba-Geigy) plus hydrocortisone acetate (20 mg b. i. d.). A total of 34 patients with advanced breast cancer entered the study: 17 were given 1,000 mg/day and 17 received 500 mg/day for at least 3 months. A novel HPLC method was developed to determine the levels of AG and its known metabolites [N-acetyl-AG (NAG), formyl-AG, nitroglutethimide, hydroxy-AG] in the biological samples. AG plasma concentration was significantly higher during the 1,000-mg/day regimen. NAG was the only metabolite observed in plasma, always occurring at concentrations lower than those of the parent drug. The ratios between NAG and AG levels distinguish two statistically different groups of patients. Irrespective of the dose, a partial response was observed in 44% of the patients; no change in 32% of cases; and progressive disease had an incidence of 24%. The probability of response was not dependent on the drug AUC or on the NAG/AG ratio and did not significantly depend on previous hormone treatment. Neither the plasmatic level of the AG or metabolite concentrations nor the NAG/AG ratio seemed to affect the incidence of side effects.

Chemotherapeutic treatment in unresectable nonsmall cell lung-cancer (nsclc) - a further attempt to modulate Cisplatin, vinblastine and mitomycin-C (pvm) schedule.

Searching for a more appropriate PVM (cisplatin, vinblastine and mitomycin-C) schedule against NSCLC, we treated 62 patients with unresectable NSCLC (49 males and 13 females), with the following regimen: high-dose cisplatin, 120 mg/m(2) i.v., day 1; common-dose vinblastine, 6 mg/m(2) i.v., day 1, and low-dose-mitomycin-C, 6 mg/m(2) i.v., day 1, repeated every 3 weeks, until progression or tolerance. Following a minimum of 2 courses, responses, by extent of disease, were as follows: in 16 patients with stage IIIB: 2 CR, 5 PR (total response rate, 44%), 8 SD and 1 PD; in 42 patients with stage IV: no CR, 15 PR (total response rate, 33%), 18 SD and 13 PD. Overall response rate was 35% with (95%) confidence limit range 23%-47%. In all the series, median duration of response was 17 weeks (range, 4-98 wks) and median time to progression 26 weeks (range, 7-111 wks). Drug related toxicity was WHO grade III and IV, leucopenia: in 30% and 11% of patients, thrombocytopenia in 27% and 10% of patients, respectively. Twelve patients (19%) developed severe anemia requiring transfusions. Three out of 5 patients dismissed treatment due to irreversible nephrotoxicity. No pulmonary toxic effect was recorded and no drug related death occurred. Fifty out of 62 patients (81%) received full doses as scheduled and 12 (19%) required cisplatin-dose reduction alone from 30% to 50%. Median duration of survival, in overall patients, was 27 weeks (range, 2-144 wks). Our results were in line with those of literature; this schedule with low-dose mitomycin-C and a single-dose vinblastine per course, seemed well feasible and safe. However, we recommend a cisplatin dose reduction to 80-90 mg/m(2) to optimise this schedule.

c-erbB-2 and common prognostic factors in breast cancer patients.

We report data on c-erbB-2, hormone receptors, and Ki-67 proliferation associated antigen in ninety-seven unselected breast carcinoma specimens. Immunohistochemical results and clinical data (age, axillary nodal involvement, menopausal status, tumor size) were compared. Positivity for c-erbB-2 staining was detected in the 46% of tumors. There was no correlation among c-erbB-2 status and age, menopausal status, tumor size, lymph nodes involvement or Ki-67 index. An inverse relationship of c-erbB-2 and estrogen and progesterone receptor status was detected, although not statistically significant. Increased levels of c-erbB-2 were observed in 40-50% of all the subsets of patients grouped on the basis of established prognostic factors. These higher levels could lead to the identification of further subsets of patients at higher risk of relapse. However, at present, the role of c-erbB-2 for clinical management of patients with breast cancer remains unclear.

Factors influencing response to second-line treatment with teniposide (VM26) in patients with progressive small cell lung cancer (SCLC).

Twenty-eight patients with small cell lung cancer (SCLC), 12 with limited (LD) and 16 with extensive (ED) disease, 22 of them relapsed to first-line treatment and 6 not responsive, were treated with a single-agent second-line treatment consisting of teniposide (VM26) 60 mg/m2, i.v. on days 1 to 5, every three weeks, until progression. After a minimum of two courses, we observed no complete response, 7 (LD/ED = 4/3) partial responses (25%), 4 (LD/ED = 2/2) minor responses (14%), and 17 (LD/ED = 6/11) with no change (61%). Median duration of response (partial plus minor) was 3.5 months (range 1-8). Median duration of survival, from VM26 administration, was in LD 6 months (range 2.5-11), in ED 3 months (range 1.5-6) and in all patients 4 months (1.5-11). Correlating the 11 responses with major prognostic variables present in the patients, we observed that KPS > 70, few initial courses of PL/VP16 and response to first-line treatment were significant determinants for successful salvage treatment. This study suggests the need to consider detailed patient characteristics of exposure to previous treatment before prompting new drug phase II studies on SCLC.

Teniposide (VM26) as second-line treatment for small cell lung cancer.

Twenty-six out of 53 patients with small cell lung cancer (SCLC) who relapsed or progressed following a first treatment (induction plus maintenance), were treated by a second-line chemotherapy consisting of: Teniposide (VM26), 60 mg/m2 i.v., days 1-5, every 3 weeks until further progression. The response rate obtained in 24 evaluable patients was: 7 (29%) partial response, 4 (17%) minor response, 8 stable disease, 5 progressive disease and 2 patients with early death. In the whole group, median survival time from the start of VM26 treatment, was 4 months (range 1-11). These data were compared to the median survival (1.5 months, range 1-7) of the remaining 27 patients, the control group, who at the time of progression did not receive further treatment. The difference between survivals was statistically significant (Log-rank test: p less than 0.05). According to these data VM26 seemed to be active, but larger studies better focused on all clinical variables are needed before firm conclusions can be drawn.

The clinical impact of FEM regimen (5-fluorouracil, 4-epidoxorubicin and mitomycin-C) in advanced gastric cancer patients.

The activity of FEM regimen in metastatic gastric cancer patients was assessed in seventy-seven patients receiving, as palliative treatment, 5FU 600 mg/m2 i.v. on days 1, 8, 29, 36; epiADR 70 mg/m2 i.v. on days 1, 29; MIT-C 10 mg/m2 i.v. on days 1, 29. Cycles were repeated every 58 days. One patient achieved a complete response and 12 a partial response, resulting in an overall response rate of 16% (95% CI: 8% to 24%). Median remission duration was 6 months. Median survival time for all patients was 8 months. Side-effects were mild and principally in the form of leukopenia (three episodes grade III). Our results support the recent findings about the lack of effectiveness of this regimen. Although it is a safe and well tolerable chemotherapeutic combination, FEM regimen should not be recommended as routinary treatment for gastric cancer patients who are not eligible for clinical trials.

Synchronous primary hepatic lymphoma and epidermoid lung carcinoma treated with chemotherapy and surgery.

While involvement of the liver by non-Hodgkin's lymphoma is a relatively frequent event, primary liver lymphoma is an uncommon disease. We describe a case of synchronous primary hepatic lymphoma and epidermoid lung carcinoma occurring in a 61-year-old male patient. Complete remission of both diseases was achieved with a radical approach, which included combination chemotherapy and surgery. The patient has now been in persisting complete remission for 40 months after surgery.

Assessing quality of life in patients with cancer: a comparison of a visual-analogue and a categorical model.

A simple instrument for self-assessment of quality of life (QL) in patients with cancer was elaborated using a linear analogue scale (LAS). The instrument was based on five questions, exploring different functional areas; the same questions were also addressed in a parallel format, where problems were seen from an opposite point of view (positive/negative). The LAS was given to 222 patients, for a total of 372 tests collected. Internal consistency was satisfactory (Cronbach's alpha = 0.75); QL score was significantly correlated to parameters of disease. Concordance between scales, as judged by comparison of parallel formats, was statistically significant but poor. A questionnaire was then elaborated with similar items, based on a categorical scale. A direct comparison between LAS and our questionnaire was made on a group of 41 patients. Internal consistency was poor for the LAS (alpha = 0.58) and good for the questionnaire (alpha = 0.93); Spearman's rank correlation coefficients were disappointing for the LAS and good for the questionnaire; the questionnaire was judged reliable in 82.9% of cases, the LAS in 29.3% only; the questionnaire score, and not the LAS score, was significantly correlated with PS and disease status. In conclusion, many patients appeared unable to correctly interpret the visual-analogue scale; the categorical scale was more immediate and correctly understood by the large majority of patients; the correlation between score and important parameters of QL was maintained, and internal consistency was excellent, indicating a satisfactory reliability of this instrument.

Metastatic tumors of the adrenals.

Adrenals are a common site of metastasis for many solid tumors. Adrenal metastases, and related symptoms of adrenal failure, are usually overlooked in clinical practice. This is probably due to the functional compensation of the adrenal glands and to the fact that signs and symptoms of adrenal insufficiency are aspecific, and often masked by symptoms of the neoplastic disease. In some tumors in which adrenal involvement is particularly frequent, adrenal evaluation should be an essential part of the preoperative diagnostic work-up. In case of demonstration of metastatic involvement the patient could be spared a useless resection of the primary tumor. However, in selected patients, even after the demonstration of an adrenal metastasis, radical surgery could still be considered for tumors with favorable biological behaviour. In patients with widespread disease, if clinical indicators of possible adrenal involvement are present an adequate palliative therapy should be started, thus ameliorating the quality of life of the patients.

Mucocele-like tumour of the breast.

Mucocele-like (ML) lesions of the breast are rare tumours and were reported as benign lesions that histologically resembled colloid carcinoma of the breast when first described about sixteen years ago. Only subsequent reports identified ML lesions associated with ductal hyperplasia or carcinoma. The Authors report an additional case of ML tumour of the breast and review the available medical literature. A young asymptomatic woman, without family history of breast cancer, presented with a palpable breast mass. As the radiological aspect was not typical of a simple cyst, the patient underwent a fine needle aspiration biopsy which showed a doubtful pathological pattern compatible with fibroadenoma. The patient underwent surgery and the gross examination of the surgically removed mass revealed multiple aggregated cysts containing mucinous material. Microscopic examination showed a ML tumour of the breast, with aspects of cribriform ductal hyperplasia.