A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

BACKGROUND: Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. METHODS: Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. RESULTS: We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. CONCLUSIONS: A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history.

[Squamous cell carcinoma on a pleomorphic adenoma with amyloid stroma of the palate]. / Carcinome épidermoïde du palais sur adénome pléomorphe à stroma amyloïde.

INTRODUCTION: Squamous cell carcinoma ex-pleomorphic adenoma (CXAP) is a malignant and rare mixed tumor. We report a new case. OBSERVATION: A seventy-year-old woman consulted for a mass in the left hemi-face having evolved over the last 20years. The physical examination revealed a hard and large tumor invading all the palate. Computed tomography revealed a heterogeneous 8.5cm long maxillary mass. The diagnosis of CXAP was made on a biopsy. A histological study confirmed the diagnosis after surgical resection of the tumor, specifying its noninvasive character. DISCUSSION: CXAP is generally located in the parotid gland; it is very rarely located in the palate. The degenerated epithelial component generally corresponds to an adenocarcinoma or an undifferentiated carcinoma; squamous-cell carcinoma is more rarely reported. The prognosis is excellent for the micro and noninvasive types. Surgery remains the treatment of choice.

[Esophageal leiomyomatosis revealing an Alport syndrome]. / Léiomyomatose oesophagienne révélatrice d'un syndrome d'Alport.

Alport syndrome is a rare progressive hematuric nephropathy associated with sensorineural deafness. Leiomyomatosis associated with Alport syndrome is quite rare. We report a particular case of Alport syndrome which was diagnosed in the setting of an oesophageal leiomyomatosis. Alport syndrome and leiomyomatosis are caused by mutation of the genes encoding for the alpha chain of type IV collagen. In view of the important clinical and genetic implications, renal function and urinary status should be controlled in any patient with oesophageal leiomyomatosis.

[Amelanotic spitzoid melanoma of the digit: case report]. / Melanome spitzoide achromique du doigt: à propos d'une observation.

BACKGROUND: Melanomas of digit is rare, accounting for 1% of all cutaneous melanomas. We report a new case. AIM: Our purpose is to discuss the clinicopathological characteristics and the difficulties encountred in establishing diagnosis of this rare tumor. OBSERVATION: we report the case of a 25-years-old woman, who consulted for nodular and ulcerated lesion of the right index, located in the external face of the metacarpo-phalangeal joint. The nodule was biopsied and histopathologic exam concluded to spitzoid melanoma. The surgical margins were involved. The patient refused surgical recovery. She consulted 3 years later with axillary lymph nodes. A wide excision of the tumor with lymph node biopsy were made. Histological study concluded to a tumoral residu incompletely excided with lymph node metastases. Amputation of the second digit with dissection of the axillary lymph nodes was made. The surgical margins were tumor free. Lung metastases appeared with a follow up of two months. The patient died early after starting chemotherapy with Deticen. CONCLUSION: In our report, clinical presentation was misleading causing a diagnosis and therapeutic delay. Pathologically, all the histological types of melanoma were described in the digit except spitzoid melanoma.

Pediatric high grade gliomas: Clinico-pathological profile, therapeutic approaches and factors affecting overall survival.

INTRODUCTION: Pediatric high grade gliomas are rare tumors of the central nervous system. Treatment is multidisciplinary, comprising surgical excision followed by radiotherapy and/or chemotherapy. OBJECTIVES: describe these tumors' characteristics as seen in our institution, and identify factors associated with better overall survival. PATIENTS AND METHODS: We conducted a retrospective study of 30 cases of pediatric high grade glioma treated consecutively in our institution over a 20-year period. Brainstem tumors and patients aged more than 22years were excluded. Univariate analysis was conducted to determine factors associated with better overall survival. RESULTS: The series comprised 30 pediatric high grade gliomas: 27 glioblastomas and 3 anaplastic astrocytomas. The sex ratio was 1.7. Mean age was 13years. Tumors were mainly located in the cerebral hemispheres (63.3%). Median tumor size was 5cm. Glioblastomas were subdivided into 26 cases of classical subtype (96.3%) and 1 case of epithelioid subtype (3.7%). Surgical strategy consisted in tumor resection in 24 cases (80%). Twenty-one patients (70%) received postoperative radiotherapy. Therapeutic response at end of treatment was complete in 7 cases (23.3%). Postoperative radiation therapy and complete treatment response were significantly associated with improved overall survival in all high grade gliomas and also specifically in glioblastomas (P<0.001 and P=0.005, respectively). CONCLUSION: Our results suggest that postoperative radiotherapy and complete treatment response are predictive factors for better overall survival in pediatric high grade glioma.

[Unusual tumor of the stomach]. / Tumeur inhabituelle de l'estomac.

Stomach melanomas are exceptional and often secondary to cutaneous tumors. Their symptomatology is not specific. We report the case of a 66-year-old woman, hospitalized with a three month history of epigastric pain and weight loss. Gastroscopy had revealed a polyp of the gastric mucosa. Histopathologic examination confirmed the diagnosis of a gastric infiltration by a melanoma. At exploration, there were lung, liver and bone metastasis and no cutaneous melanoma. The diagnosis of polymetastasis from a melanoma without primitive was kept. The patient died three months later.

[Breast metastasis: anatomoclinical study of six cases]. / Les métastases mammaires: étude anatomoclinique de six cas.

INTRODUCTION: Breast metastases are rare. They represent 0.4 to 6% of all breast cancers. Our aim is to discuss the means of diagnosis and the clinicopathological features. PATIENTS AND METHODS: We report a retrospective survey of six cases of breast metastases diagnosed over a period of 11 years (1992-2003) in the laboratory of anatomy and pathological cytology of the university hospital of Sfax. The diagnosis was carried on a material of cytoponction in two cases, a biopsy in three cases, a surgery specimen in one case. Immunohistochemical study was performed in four cases. Clinical, therapeutic and evolutionary data were collected from the files of patients. RESULTS: Metastases to the breast constituted 0.43% of all breast cancers. The primary tumors understood a case of gingival-maxillary non-Hodgkin's lymphoma, a case of retroauricular melanoma, a case of soft tissue leiomyosarcoma, a case of uterine choriocarcinoma, a case of rectal neuroendocrine carcinoma and a case of gastric signet cell carcinoma. All patients were women, the middle age was 45.5 years. In three cases the metastases to the breast was concomitant to the diagnosis of the primitive tumour. Clinically it was a nodule in five cases, the size average was 2.3cm, and a subareolar thickening in one case. The mammary involvement was bilateral in two cases. The middle survival after the diagnosis was eight months. CONCLUSION: Metastases to the breast must be distinguished from primary breast cancers whose treatment and outcome are different. A confrontation of clinical and pathological data is recommended for an accurate diagnosis. Immunohistochemical study is of great interest particularly when the breast tumour is revealing the disease.

(AC) dinucleotide repeat polymorphism in intron 1 of human EGFR shows ethnic specificities and high evidence for association with breast cancer.

A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (chi2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (chi2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity.

[Metastatic signet ring cell carcinoma to the breast from stomach]. / Métastase mammaire d'un adénocarcinome à cellules en bague à chaton gastrique.

Metastatic tumors in the breast are quite rare and constitute 0.5 to 6% of all breast malignancies. They often occur in a polymetastatic context. The most frequent primitive tumors are lymphoma, leukaemia and malignant melanoma. The gastric origin is seldom reported. We report here the observation of a 40-years woman operated in urgency for an acute abdominal syndrome. A gastric tumor was discovered intraoperatively with ovarian metastasis and peritoneal carcinosis. The pathological examination revealed a gastric signet ring cell carcinoma with an infiltration of the right ovary. Four months later, the patient presented with a lump of the right breast. The histologic examination corresponded to a mammary metastasis by a signet ring cell carcinoma from stomach. The objective of our work is to discuss through this observation the anatomoclinical and evolutionary characteristics of breast metastasis.

[Clinical case of the month. Histological discovery of a lung cancer in an enormous emphysematous bulla]. / Le cas clinique du mois. Découverte histologique d'un cancer du poumon dans une énorme bulle d'emphysème.

The development of a lung cancer in young patients with emphysematous bullae is a classical, albeit rare, event. These patients can however be operated upon for the resection of a giant bulla causing respiratory distress. We report the case of a 41 year old male patient who was submitted to the resection of a giant right apical emphysematous bulla. The histopathological examination of the fragment revealed an undifferentiated lung carcinoma the diameter of which was less than one centimeter. This observation underlines the need for a systematic examination of the resected material and for a careful radiological follow-up of such patients.

[Renal medullary carcinoma: a case report]. / Le carcinome médullaire du rein: une observation.

Renal medullary carcinoma is an aggressive malignant tumour, recently reported in the literature. It is usually reported in the relatively young patients with drepanocytic trai. Histologically, the tumour is constituted by a tumoral proliferation with diffuse or glandular architecture and inflammatory stroma. The carcinomatous cells have plasmocytoid or rhabdoid aspect. We report a case of 40 years old man who presented macroscopic hematuria. Through this observation and the review of the literature we discuss the anatomoclinical and the prognostic aspects of this exceptional tumour.

[Medullary compression revealing the presence of a follicular lymphoma: a case report]. / Compression médullaire révélatrice d'un lymphome folliculaire: à propos d'un cas.

Epidural localization is a rare presenting sign of non-Hodgkin's lymphoma. These tumours are classified in the majority of cases as large B cell lymphomas. Low grade lymphomas are rarely reported. We report a 43-year-old woman admitted for a total functional disability of the two lower limbs. Magnetic resonance imaging revealed a spinal epidural mass extending from D7 to D9. A laminectomy was performed. The histopathological study revealed a follicular lymphoma. The patient underwent a spinal irradiation and chemotherapy. Follow up evaluation at 16 months demonstrated no evidence of relapse. Our purpose is to describe the clinical features, the pathologic findings, the treatment and the prognosis of non-Hodgkin's lymphoma revealed by an epidural involvement.

[Pelvic actinomycosis: two cases]. / Actinomycose pelvienne: à propos de deux cas.

INTRODUCTION: Actinomycosis is a chronic suppurative granulomatous disease caused by different Actinomyces species, mostly bacillus: the Actinomyces israeli. The pelvis location of this infection is rare. OBSERVATIONS: We report two cases of actinomycosis that were diagnosed after the surgical treatment of a suspected ovarian tumor and a suspected acute peritonitis. Diagnosis in both cases was based on the histopathologic findings. CONCLUSION: The incidence of pelvic actinomycosis is increasing since 1960 related to the frequent use of intra uterine device. The clinical symptomatology is not specific, simulating a neoplastic or an inflammatory process. The treatment combines operative and antibiotic therapy.

[Granulosa-cell tumor of the ovary: report of 16 cases]. / Tumeur de la granulosa de l'ovaire: à propos de 16 cas.

OBJECTIVE: The aim of this work was to describe the epidemiological, pathological and clinical features of granulosa cell tumors and to study the different prognostic factors in order to determine an appropriate therapeutic attitude. PATIENTS AND METHODS: We proceeded with a retrospective study of 16 cases of granulosa cell tumors of the ovary diagnosed over a period of 10 years (1994-2003). These cases included one case of juvenile type and 15 adult types. RESULTS: Mean patient age was 46 years for the adult type (range 20-70 years) and 35 years for the juvenile type; 19% of the patients were nulliparous, 31% were menopausals. The predominant symptom was abdomino-pelvic pain with frequent hormonal manifestations. Mean tumor size was 10.5 cm with a solido-cystic aspect in 50% of cases. The treatment was surgical in all cases. Among the 16 patients, 14 (87.5%) were diagnosed at stage I and one (6.2%) at stage II. The juvenile tumor was at stage IV at time of diagnosis and only adjuvant chemotherapy was given. No relapse nor recurrence were noted for the adult type after a mean follow up of 2 years 2 months. For the juvenile form, locoregional recurrence with liver metastasis developed after 9 months. CONCLUSION: Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. The juvenile forms are more exceptional and more aggressive. A prolonged post therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form but frequent and early for the juvenile form.

Telangiectatic osteosarcoma of the rib: a rare entity and a potential diagnostic pitfall.

Osteosarcoma (OS) is a common primary malignant tumor of bones that produces osteoid matrix. Telangiectatic osteosarcoma (TOS) is a rare variant of OS. It affects the long bones especially the lower end of femur and the upper ends of tibia and humerus, a distribution similar to the conventional osteosarcoma. The rib involvement is very infrequent. We present a case of TOS of the rib that posed a diagnostic difficulty owing to its unusual location and to its resemblance to giant cell tumor and aneurysmal bone cyst. Correspondence.

[Feminizing testicular syndrome with multiple hamartomas and bilateral paratesticular leiomyomas]. / Syndrome du testicule féminisant associé à des hamartomes multiples et à des léiomyomes paratesticulaires bilatéraux.

INTRODUCTION: Complete androgen insensitivity syndrome or testicular feminization syndrome (TF) is the most common form of male pseudohermaphrodism, caused by a failure of androgen receptor binding. Patient with male genotype 46 XY, has a female morphotype with well developed external sexual organs. EXEGESIS: - We report the case of a 29 year-old girl with a TF syndrome discovered during the exploration of a primary amenorrhoea. Bilateral orchidectomy was performed. The testis were immature; they showed bilateral leiomyoma of the tunica albuginea and multiple hamartomas on the right side. CONCLUSION: Benign tumors are developped in 80% of cases of TF and they are generally hamartomatous nodules of testis. Association of paratesticular leiomyoma to synchronous hamartoma has never been described, its histogenesis is discussed.

An unusual tumour of the lung.

We report a case of a 51-year-old woman with a solitary mast cell tumour of the lung, a rare neoplasm with only three previously-reported cases reported in the literature. Unlike previous cases, the tumour in the present case was bulky, measuring 14 cm in diameter and budding into the segmental bronchus. Histologically, it showed proliferation of typical metachromatic mast cells intermingled with undifferentiated cells with a ratio of 3:1. The neoplastic mast cells stained strongly with tryptase, CD117, CD68 and CD45, CD14 and CD33; whereas the undifferentiated cells lacked all these markers and expressed EMA and cytokeratin. Histological examination of bone marrow and laboratory data were unremarkable. To our knowledge, this is the fourth case of solitary extracutaneous mastocytoma of the lung. The differentiating features of this neoplasm and a review of literature are presented.

[Verrucous carcinoma of the kidney: report of 2 cases]. / Carcinome verruqueux du rein: à propos de deux cas.

The verrucous carcinoma is an unusual shape of well differentiated squamous cell carcinoma, first described at the ORL region; the kidney location is rare; the risk factors are represented essentially by lithiasis and/or urinary infection; the clinical symptom is not specific. Diagnosis is facilitated by radiological investigations and particularly excretory urogram/ultrasound; certainly diagnosis is pathological. The nephro-ureterectomy with collar resection of the bladder is the choice treatment. We report two observations and we clarify clinicopathological aspects of this type of carcinoma and we discuss the prognosis.