Penetration of amphotericin B in human lung tissue after single liposomal amphotericin B (AmBisome) infusion.

The distribution of amphotericin B in lung tissue was studied in 18 patients with primary or secondary lung cancer who underwent thoracotomy and pulmonary resection. At different times before surgery the patients were treated with liposomal amphotericin B 1.5 mg/kg by i.v. infusion over 1h. Blood and lung tissue samples were collected during surgery (one subject for each collecting time) and assayed for amphotericin B levels by HPLC. Due to surgical requirements, it was possible to obtain data from the 10th to the 25th h after the end of infusion. Plasma amphotericin B concentrations progressively decreased from 3.4 microg/ml at the 10th h to 1 microg/ml at the 25th h after the end of intravenous infusion. In lung tissue samples the lowest amphotericin B concentration (about 1 microg/g) was observed at the 10th h, then a progressive increase was observed with the highest value (2.5 microg/g) determined at the 25th h.

Minimally invasive thoracic surgery for diagnostic assessment and palliative treatment in recurrent neoplastic pleural effusion.

BACKGROUND: We evaluated the effectiveness of VATS in the diagnosis and palliative treatment of recurrent neoplastic pleural effusions. METHODS: From 1987 to 2001, we performed 325 VATS chemical pleurodesis for malignant pleural effusions. We used talc in 253 subjects (78 %) and alcohol in 72 (22 %) as the sclerosant agent. In 226 patients (68 %) we performed biopsies because the histology was unknown. RESULTS: Mean operating time was 33.38 +/- 9.77 minutes (median: 32; range: 19 - 58), and the mean duration of chest intubation was 3.78 +/- 1.33 days (median: 4; range 2 - 8). Complications occurred in 2 % of patients. Thirty-day mortality was 2 %. Mean postoperative in hospital stay was 5.53 +/- 1.90 days (median 6; range: 2 - 11). We obtained 264 (81 %) therapeutic successes (no effusion recurrence within 4 months), and 55 relapses of which 32 had talc insufflation (13 % of talc group) and 23 alcohol instillation (32 % of alcohol group). CONCLUSIONS: VATS chemical pleurodesis is a safe, useful, versatile procedure for oncological pleural effusion management. The use of talc rather than alcohol significantly increased the therapeutic success rate. VATS should be considered the treatment of choice in patients with advanced neoplasm to obtain good palliation and a better quality of life.

[The role of surgical therapy for esophageal microcytoma. Experience of there clinical cases and results analysis]. / Il ruolo della terapia chirurgica nel microcitoma dell'esofago. Esperienza di tre casi clinici ed analisi dei risultati.

Small cell carcinoma of the esophagus is a rare tumor. It was described for the first time in 1952 by McKeown and 200 cases have been reported till now. Because of its similarity with small cell carcinoma of the lung, the treatment of this tumor is controversial. In our Institute we treated three patients with small cell carcinoma of the esophagus. All subjects underwent subtotal esophagectomy with esophagogastroanastomosis through laparotomic and thoracotomic approach. Histologically, the tumor was classified as pure SCEC in one patient and mixed SCEC in the other two. The stage I and II patients received operation as single treatment. The two patients are alive and disease free 219 and 193 months after surgery. The third patient, classified at stage III, underwent postoperative chemotherapy but local and distant recurrence was observed 11 months after surgical resection. He was submitted to a second choice chemotherapy, but he died 24 months after the operation. The long-term survival observed in our two patients treated by surgery is the longest described in literature. Our experience seems to demonstrate that an early diagnosis and oncological radical resection, may be helpful in the long-term prognosis even in presence of a very aggressive neoplasm.

[Biphasic blastoma of the lung. Report of 4 consecutive cases and evaluation of long-term prognosis]. / Il blastoma bifasico del polmone. Report di 4 case consecutivi e valutazione della prognosi a distanza.

Pulmonary blastoma is a rare malignant disease and it can occur in adults and in children. In 1952, Barnard reported the first case classified as pulmonary embryoma while in 1961 Spencer reported the first case as pulmonary blastoma. Since then 200 cases were described in literature. Four patients with adult primary pulmonary blastoma were treated in our Institute. The tumor was right sided in all cases; it belonged to upper lobe in 1 patient, to middle in 1 and to lower in 2. The patients underwent middle lobectomy in 1 case, lower lobectomy in 2 and upper lobe typical segmentectomy in one (the subject previously operated for lung adenocarcinoma). Histology detected primary pulmonary biphasic blastoma in all the cases. In only one case it was associated with hilar lymph nodal metastases. She received adjuvant chemotherapy, but after 17 months she developed distant metastases and she died 22 months after operation. About the other 3 patients: one patient died 6 months after intervention for acute cardiac disease, while two subjects are still alive and disease free 158 and 70 months after surgery. Surgical resection, when radicality could be ensured, is considered the treatment of choice, in absence of other curative therapies. The analysis of our experience confirms surgery to be a good therapeutic choice permitting to obtain long term survivals. The patient, alive ten years after the operation, is one of the longest survival case for pulmonary blastoma reported in literature.

[Use of the skin-closure system Medizip in median sternotomy in oncological patients. Evaluation of results obtained in 30 patients]. / Utilizzo del dispositivo Medizip per la sutura cutanea in caso di sternotomia mediana in pazienti oncologici. Valutazione dei risultati ottenuti in 30 pazienti.

BACKGROUND: The authors evaluate effectiveness, safety and cosmetic results obtained using the new skin closing system Medizip. METHODS: At the Thoracic Surgery Department of the National Cancer Institute (Milan) between June 1999 and March 2001, in 30 patients who underwent median sternotomy for bilateral pulmonary wedge resections, Medizip a new skin-closing system to suture the sternal wounds has been used. Twenty patients were under 30 (66%) and 6 of the 10 remaining were females. The average age was 34.25+/-21.60 years, (median: 25, range: 12-72). It took about half a minute (average time: 30.00+/-10.54 seconds) to perform all the application manoeuvres. In order to better evaluate the cosmetic results obtained, a scale of three levels was created: level 1: very good, level 2: satisfactory, level 3: inadequate. RESULTS: Twenty-eight 20 cm-long zippers, one 25 cm-long and one 30 cm-long were employed. Medizip has been kept in site for 9.88+/-2.12 days on average (median: 9; range: 8-12). The time employed for each dressing was on average 70.00+/-21.35 seconds (median: 70, range: 46-128). No wound infections were observed even if all the patients were affected by neoplastic diseases and were immunocompromised because of lots of antiblastic treatments. The quick removal (few seconds) and the non-invasiveness of the disposal constitutes remarkable advantages. Using the criteria previously described, 26 patients at level 1 (87%), and 4 (13%) at level 2 were classified. CONCLUSIONS: Medizip is considered to be an effective skin-closure system easy and quick to handle, assuring very good cosmetic results, with non-invasive removal, particularly useful in pediatric patients and in young adults affected by neoplastic diseases undergone to a lot of combined treatments.

Unsuspected residual disease at the resection margin after surgery for lung cancer: fate of patients after long-term follow-up.

OBJECTIVE: This retrospective study evaluates the survival impact of the residual margin disease after bronchial resection for cancer and suggests tactics in cases of microresidual disease. METHODS: Between March 1988 and 1998, 4530 consecutive patients underwent surgery for non-small cell lung cancer at our institution. Only incomplete resections after microscopic evaluation (R1) were included in the study. Residual tumour cells were found on the bronchial resection margins of 39 lobectomies, 12 pneumonectomies, 4 segmental resections and one bilobectomy. Histological findings were: squamous cell carcinoma in 38 cases, adenocarcinoma in 15 and large cell carcinoma in three. In all 56 cases, invasive mucosal carcinoma was found exclusively on the bronchial resection margin. Nineteen tumours were stage I; 12, stage II; 17, stage IIIa; 5, stage IIIb; and three, stage IV. Nineteen patients (59.3%) with early stage tumours (I and II) received adjuvant radiation therapy and only three chemotherapy. RESULTS: The prognosis in these cases was disease-stage related (21 and 38.4% of deaths due to the disease). Forty-one percent of the stage IIIa patients received radiation therapy and 17.6% chemotherapy: 70.6% died of tumour relapse. Forty percent of the stage IIIb patients received radiation therapy and 20% chemotherapy: 60% died of disease progression. All of the stage IV patients died within 3 months from surgical resection. At the end of the study, 21 patients were alive after an interval of 22-142 months (18 in stage I or II). The 10-year actuarial survival rate was 44%. The percentage survival for stage IIIa was 16.8, after 10 years, and fell to 45 months for stage IIIb. CONCLUSIONS: The prognosis of our stage I or II patients with microresidual tumour on the bronchial resection margin (R1) was similar to that of the patients in the same disease stage, whose resection was microscopically radical (R0) and the same was true of the patients in stage III. In patients with residual tumour cells on the bronchial stump we did not observe worsened long-term survivals.

The difficult approach to neoplastic superior vena cava syndrome: surgical option.

AIM: Superior vena cava syndrome is a dramatic event that can be cured in specialized centers. METHODS: Between 1989 and 1995 6 patients with superior vena cava syndrome underwent surgical treatment for thoracic tumors. In all cases the vena was restricted by a neoplastic sleeve. A median sternotomy was performed in all cases. Two patients received an associated right anterolateral thoracotomy to obtain good surgical exposure for tumor resection and grafting. A 12 mm diameter polytetrafluoroethylene graft was inserted in all cases. The tumor resection was radical in 4 cases (2 thymic carcinomas, 2 malignant germ cell tumors) and palliative in 2 (1 non-small cell lung cancer and 1 mediastinal fibrosis). RESULTS: We had no in-hospital mortality. All patients had immediate relief of obstruction after by-pass. Three patients were alive without disease at the end of follow-up (40-96 mo), one patient died of postoperative complications after 4 mo, 2 patients died of disease after 4 and 12 mo. CONCLUSION: PTFE by-pass graft for treatment of the obstructed SVC relieves SVC syndrome and has good medium term patency.

A particular case with long-term follow-up of rare malignant hemangiopericytoma of the lung with metachronous diaphragmatic metastasis.

The authors report the case of a woman with a primary hemangiopericytoma of the lung and successive metachronous diaphragmatic metastasis treated with surgery only according to the patient's decision. The patient was first submitted to left lower lobectomy with resection of diaphragm and three ribs en-bloc for pulmonary sarcoma. One year later, a chest computed tomography (CT) scan showed a small lesion above the diaphragm on the left side. She refused the proposed operation and returned fifteen months later with a new thorax CT, and told us that she had in the meantime become pregnant and given birth. A rethoracotomy to remove the metastatic diaphragmatic tumor was performed. Chemotherapy with anthracycline and iphosphamide was proposed, but the patient again refused therapy for fear of side effects impairing another pregnancy. Currently, the patient is alive and disease-free, 68 months after the first treatment. The authors emphasize the long-term follow-up obtained with surgery alone in this kind of rare sarcoma.

Major surgery in lung cancer in elderly patients? Risk factors analysis and long-term results.

BACKGROUND: In the Oncological Thoracic Surgery Department of the Istituto Nazionale Tumori of Milan a retrospective study was performed on lung cancer patients 70 years old or more with the aim of evaluate the role of surgical treatment and to analyse long-term results. METHODS: In our Institute from January 1988 to December 1993, 151 lung cancer patients 70 years old or more underwent surgery for lung cancer. One hundred and twenty-six of them (83%) were males and 25 were females (17%), the average age was 73.09+/-2.91 years (median: 77; range: 70-82). All the subjects were completely staged preoperatively. In order to establish operability criteria, we considered some selection parameters. Patients general conditions were evaluated using Karnofsky score accepting only the ones with 70% or more for surgery, all the cases performed cardio-respiratory functional evaluation. Patients with: a) FEV1 <60% of predicted value or FEV1 <1 l; b) PaO2 <60 mmHg e PaCO2 >40 mmHg were excluded from surgery. RESULTS: The operations performed were: 23 pneumonectomies, 6 bilobectomies, 93 lobectomies, 13 segmentectomies and 16 wedge resections. Eight cases were submitted to thoracectomy in association to pulmonary resection. Peroperative mortality was 3% and morbidity was 10%. Histological examination showed 69 adenocarcinomas, 65 squamous carcinomas, 4 large cells carcinomas, 4 typical carcinoids, 5 small cells carcinomas, 2 mucoepidermal carcinomas and 2 adenosquamous carcinomas. Eighty-six patients were classified at stage I, 38 at stage II, 24 at stage III and 3 at stage IV (multifocal disease). The actuarial 4-years global survival predicted with Kaplan Meier method was 40%, in particular it was 75% for stage I patients. CONCLUSIONS: In case of resectable primary pulmonary neoplasm, surgery represents the first choice therapy; patient's age doesn't seem to be an absolute contraindication, but it has to be evaluated with biological and not with age criteria. Using adequate selection criteria, it's possible to obtain, in patients older than 70 years, long-term survivals that don't seem to differ from global survivals.

Gastrobronchial fistula repair followed by esophageal leak--rescue by transesophageal drainage of the pleural cavity.

A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia was diagnosed six years after an esophagectomy with gastric pull-up. After failed surgical repair, an uncontained esophagopleural leak developed. Fistula closure was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became dislodged. Transesophageal drainage was positioned endoscopically through the suture-line defect and led to closure of the leak after 10 days.

Video-assisted thoracoscopic surgery for diagnosis, staging, and management of lung cancer with suspected mediastinal lymphadenopathy.

The aim of this report was to evaluate the effectiveness of video-assisted thoracoscopic surgery (VATS) in staging, diagnosis, and treatment of lung cancer. Fifty-two patients were scheduled for mediastinal lymph node VATS biopsy at the Oncologic Thoracic Surgery Department of the National Cancer Institute in Milan. Fifty patients underwent lymph nodal thoracoscopic biopsy (96%), whereas for the other 2 patients, histologic diagnosis was done by pleural metastatic nodule thoracoscopic biopsy (4%). We performed 17 lymph nodal biopsies in level 5 (33%), 14 in level 6 (27%), 12 in level 7 (23%), and 7 in level 8 (13%). No postoperative complications were observed, and 19 subjects (36%) underwent open lung resection. The histologic diagnosis was adenocarcinoma in 25 cases (48%), epidermoid carcinoma in 14 (27%), microcytoma in 9 (17%), and giant-cell lung carcinoma in 4 (8%); 10 patients were at stage I (19%), 9 at stage II (17%), 31 at stage III (60%), and 2 at stage IV (4%). The use of VATS allowed diagnosis of the suspected involved mediastinal lymph nodes in lung cancer patients and obviated the need for painful thoracotomy, enabling accurate staging and thus selection of the optimal treatment.

Clinical and pathologic predictors of survival in patients with thymic tumors.

BACKGROUND: The aim of this study is to evaluate the impact of thymectomy in patients with thymic neoplasms and to identify clinical and histopathological factors associated with improved long-term outcome of surgery. METHODS: We treated 74 patients between February 1987 and July 1993. There were 29 total and 36 simple thymectomies. These last cases, all non-myasthenic, had benign thymomas (n=30) but 6 had thymic carcinomas. Nine tumors were no-resected (5 thymomas and 4 thymic carcinomas). Minimum follow-up by Department of Thoracic Surgery Istituto Nazionale Tumori was 60 months after thymectomy. We divided the specimens according to Marino and Muller-Hermelink's classification: 54 thymomas, 18 thymic carcinomas and 2 no-diagnosis specify thymomas. There were 53 stage I, 1 stage II, 13 stage III, 5 stage IVa and 2 stage IVb according to Masaoka. RESULTS: Forty-six patients with treated thymoma were alive without disease at the end of follow-up, the remaining 8 died from recurrence in 6, a new tumor in 1 and a heart attack in the last. Of 18 thymic carcinomas 9 were alive at the end of follow-up (1 with recurrence), only 4 dead from recurrence. The actuarial survival of patients with thymomas was 88.5% at 5 years, (73.6% in cortical type, 85.7% in medullary type, 93.9% in mixed type, 100% in predominantly cortical type). Myasthenia gravis didn't influence the survival: 87.3 (no MG) vs 90%. Advanced stage thymomas significantly increased the risk of death from early stage I: 32.4 vs 100% at 5 years. In thymic carcinoma patients with well-differentiated thymic carcinoma (WDTC) died less than others: the actuarial probability of survival at 5 years was 90 vs 68%. CONCLUSIONS: Thymectomy was the best treatment to long term outcome. In our experience, survival was related to histotype and to local extension of tumor.

Surgical treatment of gastric metastases from cutaneous melanoma: experience of the National Cancer Institute of Milan.

AIM: To evaluate the role of a surgical approach in patients affected with gastric metastases from cutaneous melanoma. METHODS: A retrospective review of our local melanoma database of 2100 patients identified 31 cases with gastric metastatic deposits. Nine of them were considered candidates for surgical resection. RESULTS: Median overall survival of the 9 patients who underwent surgery was 14.2 months. Six (67%) underwent a local radical resection of disease, and 3 (33%) had a simple exploratory laparotomy. The median survival was 21.6 months (range, 4-32 months) for the subset receiving radical surgery and 3.6 months (range, 2-6 months) for the patients who had no resection. Median follow-up was 14.2 months. No specific correlation of serologic LDH levels and final outcome, as documented elsewhere, was observed. A marked decreased or substantial remission of symptoms with an improvement in quality of life was observed in all radically resected patients. CONCLUSIONS: Patients with gastric metastases from melanoma may benefit from surgery if all macroscopic disease can be removed. In addition, gastric resection in patients with symptomatic melanoma spread to the stomach provides important symptomatic palliation.

[Analysis and long-term survival in sternectomy with plastic reconstruction for primary and secondary neoplasms of the sternum]. / Analisi e sopravvivenza a lungo termine nelle sternectomie con ricostruzioni plastiche per neoplasie primitive e secondarie dello sterno.

From January 1980 to December 1999, 88 patients underwent surgical resection for tumours involving the sternum. Thirty were males, aged 16 to 76 years, and 58 females, aged 23 to 78 years (mean ages: 48 and 53 years, respectively). There were 30 primary malignant tumours, 28 local recurrences or distant metastases from breast cancer, 16 other tumours, and 14 radionecroses. Total sternectomy was performed in 8 cases, subtotal (> 50%) in 32, and partial (< 50%) in 48. Concurrent en-bloc resection of the anterior ribs was performed in 61 patients, and of the clavicle in 13. Resection was extended to the lung in 22 patients, to the pericardium in 17, to both in 2, to the diaphragm and pericardium in 4. Bone and soft tissue defects were repaired with prosthetic material associated with a muscular or myocutaneous flap in 55 patients, with prosthetic material alone in 13 cases, with a muscular or myocutaneous flap in 5 cases, and with other techniques in the remaining patients. The resection was considered to be macroscopically radical in 78 patients and palliative in 10 cases. There was one perioperative mortality and significant morbidity was limited to 13 cases. Among the patients treated with a radical intent, 48 were alive and disease-free at the end of follow-up. The 10-year survival rate was 85% in primary tumours. For breast cancer relapses, 10-year survival was the same as 5-year survival (41.8%). In our experience, an en-bloc sternal resection for a primary or secondary tumour, followed by plastic repair using prosthetic material and/or a myocutaneous flap, is a safe, effective treatment. This intervention permits the execution of extensive radical resections for sternal neoplasms, as well as enabling the patient to obtain a better quality of life. Long-term survival after radical sternectomy also depends on the histological type of the tumour.

Linkage disequilibrium pattern in the L-myc gene in Italian and Japanese non-small-cell lung-cancer patients.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3-3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism.

[Significance of video-assisted thoracoscopic surgery in the diagnosis and staging of primary pulmonary neoplasms]. / L'importanza della chirurgia toracoscopica video-assistita nella diagnostica e nella stadiazione delle neoplasie polmonari primitive.

The authors describe the usefulness of video-assisted thoracoscopic surgery (VATS) in the staging and diagnosis of primary lung cancer. In the Oncological Thoracic Surgery Department of Milan's National Cancer Institute, over the period from January 1995 to January 2000, 46 patients, suspected of having mediastinal lymphadenopathies in the presence of lung cancer, were proposed for a VATS biopsy. Forty-four patients underwent a thoracoscopic lymph node biopsy (95%), while in 2 subjects, in whom pleural metastases were found, the histological diagnosis was established by pleural metastatic nodule thoracoscopic biopsy (5%). A VATS lymph node biopsy was performed in 16 cases at level 5 (35%), in 13 at level 6 (28%), in 9 at level 7 (19%) and in 6 at level 8 (13%). Lymph node biopsies were ipsilateral in 37 patients (80%) and contralateral in 7 (15%). No postoperative complications were observed. Histological examination revealed adenocarcinoma in 23 cases (50%), epidermoid carcinoma in 12 (26%), microcytoma in 8 (17%) and giant-cell lung carcinoma in 3 (7%). Two patients were classified as stage IV (5%), 7 as stage III B (15%) and 21 as stage III A (45%). The subsequent treatment was neoadjuvant chemotherapy for stage III A patients and chemotherapy in association with radiotherapy for stage III B subjects. The patients with microcytoma underwent integrated radiotherapy and chemotherapy and pan-encephalic radiotherapy. Sixteen patients, with negative frozen-section histological findings for mediastinal lymph node neoplastic disease, underwent pulmonary resection after thoracotomy in the same operating session (35%) and were subsequently classified as stages I and II. In conclusion, VATS proved extremely useful in the diagnosis and staging of patients affected by lung cancer with synchronous lymph node enlargement. This procedure allowed the diagnosis of suspect involved mediastinal lymph nodes in all cases thus affected and the exclusion of lymph node disease in patients subsequently treated by lung resection in a single session. The precise staging obtained then made it possible to direct the patients towards the most appropriate form of treatment.

Unusual association between cutaneous melanoma and axillary metastasis from occult breast cancer detected by sentinel node biopsy.

We report a case of cutaneous Stage I melanoma associated with occult breast cancer detected incidentally during a sentinel node biopsy. A brief review of the literature is presented with particular emphasis on this association and on an examination of the theoretical link which may exist between melanoma and breast cancer.

[Pulmonary metastasis of basal cell carcinoma of the skin. 3 case reports]. / Le metastasi polmonari da carcinoma basocellulare della cute. Presentazione di tre casi.

The Authors describe three cases of lung metastasis from a basal cell carcinoma of the skin observed in the Department of Thoracic Surgery of the National Cancer Institute in Milan. The incidence of this rare occurrence reported in the literature is approximately 0.1%, The aim of the study was to evaluate the therapeutic treatment adopted in these unusual situations. In all cases the primary basal cell carcinoma of the skin was located in the head. All three patients had several local and regional recurrences and underwent multiple surgical excisions and subsequent plastic procedures. In each case complementary radiotherapy was implemented. The metastases appeared in the lung 9, 17 and 21 years, respectively, after onset of the primary tumour as bilateral nodules in two cases and as a single nodule in one. Curative surgery was possible only in one subject, consisting in a bilateral metastasectomy via a midline sternotomy, with 5-year survival. Surgery was withheld in the other two subjects owing to advanced age and the presence of bilateral nodules with concomitant bone metastasis, respectively. Both were treated by chemotherapy and the patient with synchronous bone metastasis also received radiotherapy. The elderly subject died after six months, and the other patient after 19 months despite partial remission of disease. In our experience, curative therapy proves difficult due to multiple metastases. In the literature there are few reports regarding this rare type of metastatic lung disease, but surgical intervention would appear to be the therapy offering the best chance of long-term survival while chemotherapy constitutes the second-choice treatment.

Association between cutaneous melanoma and neurofibromatosis type 1: analysis of three clinical cases and review of the literature.

The authors report a rare association between cutaneous melanoma and Von Recklinghausen's disease (NF-1) and analyze the possible meaning of this occurrence. Various types of tumors have been associated with NF-1, in particular those of neuroectodermal origin, such as malignant peripheral nerve sheath tumors (MPNST) and phaeochromocytoma. The development of malignant melanoma in NF-1 patients is rare. Data from the literature is enable to demonstrate an increased incidence of cutaneous melanoma in patients with neurofibromatosis but the association of these two disorders seems reasonable in theory, as both are abnormalities of a neural crest origin. The cases described may represent not only a clinical report of two rarely associated disorders, but may also confirm the biological mechanisms responsible for these infrequent diseases.