Adolescents and young adults with classical Hodgkin lymphoma in northern Tunisia: insights from an adult single-institutional study.

PURPOSE: The aim of this study was to extensively describe the epidemiological, clinical and therapeutic outcomes of adolescents and young adults (AYA) population with classical Hodgkin Lymphoma (cHL). Then, a comparison between AYAs and adults and between the subgroups of AYAs treated with the same adult protocol was accomplished to further inform on optimal therapy approach of choice for adolescent patients. MATERIAL AND METHODS: In this mono-centric, retrospective study, we reviewed the medical records. We analyzed 112 consecutive North Tunisian patients, including 66 AYAs (15 to 39 years) and 46 adults (≥40years) affected by cHL treated from 2000 to 2015 at Salah Azaiez Institute. Then, we performed a comparative analysis between AYA and 46 adult patients and a subgroup analysis between adolescents and young adults. All patients were treated according to the national protocol for HL, edited by the Tunisian Society of Hematology. The treatment included chemotherapy and involved-field radiotherapy (RT) at a dose of 20 or 30 Grays (Gy) for responders and 36Gy for non-responders. RESULTS: AYA patients presented with adverse features with nodular sclerosis subtype (p=3.88×10-02) and mediastinal mass involvement (p=9.40×10-04). At a median follow-up of 51 and 32 months for AYAs and adults, respectively, no statistical difference in terms of 3 and 5-years overall survival (OS) and event-free survival (EFS) was shown. Using the Kaplan-Meier method, in AYAs, the ABVD regimen has an impact on 3-years EFS (p=4.63×10-02). The 36Gy RT was associated with the best 3-years EFS (p=9.24×10-03). Besides, AYA patients with advanced-stage had the worst 3-years OS (76%) (p=2.41×10-02). Although the adolescents and young adults shared similar clinical presentation, we noted that the adolescent group had the worst 3-years EFS (48%), but the best 3-years OS (91%). We identified 15% of primary refractory patients and a rate of toxicity of 5.3% in AYA. CONCLUSION: The treatment approach used is well tolerated by adult patients. However, the AYA patients and particularly adolescent subgroup had more advanced disease at diagnosis and should be treated more intensively in dedicated units. RT dose<36Gy and ABVD chemotherapy were associated with lower EFS in this population.

[Primary breast sarcomas: About 30 cases treated at Salah-Azaiez institute in Tunisia]. / Sarcomes mammaires primitifs : à propos de 30 cas traités à l'institut Salah-Azaiez de Tunis.

PURPOSE: To identify retrospectively prognostic factors of primary breast sarcoma and review its treatment modalities. MATERIALS AND METHODS: This is a descriptive study on 30 cases of primary breast sarcoma. We carried out a univariate and multivariate analysis correlating clinical, pathological and therapeutic parameters with disease-free survival and overall survival. RESULTS: The mean age was 46.8 years. The mean tumour size was 10cm. The 30 cases were 18 phyllodes sarcomas, eight angiosarcomas, three liposarcomas and a case of granulocytic sarcoma. Sixteen patients had adjuvant radiotherapy and only seven patients received adjuvant chemotherapy. The median follow-up was 64 months. Overall survival rates at 3 and 5 years were 49.1% and 33.7%. Disease-free survival rates at 3 and 5 years were 22.8% and 15.2% respectively. The analytical study of the following parameters: tumour size and presence or absence of node or distant metastases, showed no correlation with overall survival nor with disease-free survival. Furthermore, adjuvant radiotherapy did not improve overall survival (P=0.298; hazard ratio [HR]=1 [0.982-1.04]) nor disease-free survival (P=0.61; HR=0.942 [0.862-1.029]). By univariate analyses, we identified a correlation between overall survival, surgical margins (>1cm) (P=0005; HR=3.4 [1.217-9.919]) and tumour necrosis (P=0.028; HR=0.099 [0.014-0.682]). We did not find any independent prognostic factor by multivariate analysis. CONCLUSION: The prognosis of primary breast sarcoma seems to depend essentially on optimal surgical excision (margin over 1cm). The only potential histological parameter correlated with the prognosis is the presence of tumour necrosis. The histological subtype should not be considered as a prognostic marker for overall or disease-free survival in patients with primary breast sarcoma.

Usefulness of IGF-1 serum levels as diagnostic marker of nasopharyngeal carcinoma.

BACKGROUND: The role of IGF-1 in promoting cancer has been investigated for many years. The aim of this study is to explore the relationship between rates of IGF-1 and NPC and to evaluate association of IGF-1 with clinical parameters. MATERIALS AND METHODS: IGF-1 levels was measured by Elisa test among 82 NPC patients and 60 healthy controls RESULTS: Our results showed, for the first time, a significant increased levels of IGF-I in NPC by in comparison with healthy controls (p<0.01). According to the age, sex and tumor size of NPC patients, we demonstrated that IGF-1 concentrations are significantly higher in NPC aged over 30 years compared to patients aged less than 30 years (p<0.01). The IGF-1 levels are, also, higher among women compared to men (p<0.01). The concentrations of IGF-1 were positively correlated with tumor size of NPC patients (p<0.01). CONCLUSION: IGF-I could be a good nasopharyngeal cancer diagnostic marker.

[Dirofilariasis of the breast: Two new cases in Tunisia]. / Dirofilariose mammaire: à propos de deux nouveaux cas en Tunisie.

Dirofilariasis is an endemic animal parasitic disease in the Mediterranean basin. Its occurrence in humans is rare; when it occurs, it is most often in cutaneous locations. We report two new cases of dirofilariasis of the breast in two Tunisian women, aged 32 and 45 years old. Both came from northern Tunisia and consulted for breast lumps. Clinical examination and imaging findings suggested benign tumors. After surgical excision, the pathology examination confirmed the diagnosis, based on the presence of Dirofilaria repens in the specimen. Dirofilariasis prevalence is probably underestimated because of its non-specific clinical presentation. Breast locations are rare and frequently consist of tumors with benign features. Surgical resection confirms the diagnosis and is the only treatment.

Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early-onset breast/ovarian cancer from Tunisia.

The contribution of BRCA1/BRCA2 mutations to hereditary breast cancer in the Tunisian population has not been accurately estimated. The purpose of our study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in early onset and familial breast/ovarian cancer among Tunisian women. To identify predictive factors for BRCA1/2 mutations, we screened the entire coding sequences and intron/exon boundaries of BRCA1/BRCA2 genes in 48 patients by direct sequencing. Twelve pathogenic mutations were detected (25%); three in BRCA1 (c.211dupA in four families, c.5266dupC in three families and c.1504_1508delTTAAA in one family) and two novel mutations in BRCA2 (c.1313dupT in two families and c.7654dupT in two families). We also identified 23 different polymorphisms and unclassified variants. These results indicate that our population has a spectrum of recurrent BRCA mutations.

[Metabolic profile of Tunisian obese adult]. / Profil Métabolique de L'adulte Obèse Tunisien.

BACKGROUND: Obesity is associated with multiple comorbidities such us metabolic and cardiovascular diseases. AIMS: Evaluate metabolic profile and to determinate the frequency of metabolic syndrome in Tunisian obese adult. METHODS: It's a prospective study realized in the unit of obesity research in the national institute of nutrition between April 2003 and March 2005.This study concerned two groups of subjects aged between 20 and 60 years old : Group 1 (n = 100) obese (BMI (3) 30 kg/m2) and group 2 (n= 60) controls with normal weight (BMI between 18,5 and 24,9 kg/m2). RESULTS: Mean number of metabolic complications is significantly higher (P < 10-3) in obese (3,28 +/- 2) than in controls (1,16 +/- 1,2). Impaired fasting glucose and type 2 diabetes mellitus are respectively more frequent in obese (37 % and 16 %) than in non obese (5 % et 1,7 %). Hyperinsulinemia is significantly (P<10-3) more frequent in obese. hypertriglyceridemia, hypercholesterolemia and hyperapolipoproteinaemia B are significantly (P = 0,01, P < 10-3 et P < 10-3) more frequent in obese than in no overweight subjects. The prevalence of hyperuricemia increased significantly (P = 0,01) in overweight subjects than in normal weight subjects. Metabolic syndrome is significantly more frequent (P < 10-3) in obese (48 %) than in control (1,7 %). CONCLUSION: Obesity, especially visceral obesity , is associated with a cluster of metabolic complications increasing the risk of coronary heart disease. We stress on the importance of primary prevention and early management of obesity.

[Sentinel node in breast cancer. Experience of the Salah-Azaïz Institute of Tunis]. / Le ganglion sentinelle dans le cancer du sein. Expérience de l'institut Salah-Azaïz de Tunis.

INTRODUCTION: Breast cancer screening increased the ratio of small tumours. These tumours have a low lymph node metastatic potential. Sentinel node detection allows detecting axillary lymph node invasion without the morbidity of complete axillary lymph node dissection. OBJECTIVES: In this study we report the results of the learning curve of sentinel node detection in the Institut Salah-Azaïz of Tunis. MATERIALS AND METHODS: It is a prospective study between January 2004 and December 2005 in which 115 patients were included with breast cancer less than 3 cm without antecedents of breast surgery. All these women had sentinel node dissection by a colorimetric method and 30% had a combined method (colorimetric and isotopic). RESULTS: The rate of detection was 97.3% (n = 112). An extemporaneous examination was performed in 91 patients. The rate of negative forgery of the extemporaneous examination was 4.3% and the sensitivity of 95.7%. There are no false positive with the extemporaneous exam. The sentinel lymph node was the only node invaded in 15 patients (44%). In 3 patients, the sentinel node was healthy whereas the axillary dissection was positive, so the false negative rate is about 2.6%. CONCLUSION: Sentinel node dissection is a reliable and feasible technique. It however requires a training of the surgeon, the pathologist and the nuclear doctor. It allows to reduce the morbidity of the treatment of the breast cancer by avoiding "useless" axillary dissection out in patients without node invasion. The increase in the number of the small cancers discovered during screening makes it possible to increase the number of patients who can profit from this technique.

[Radio-histological correlation of microcalcifications of the breast: a Tunisian center experience]. / Corrélation radio-histologique des microcalcifications du sein. Experience d'un centre Tunisien.

PURPOSE: Evaluation of surgical biopsy for mammary microcalcifications, in Tunisian patients according to the American College of Radiology's recommandations (ACR). MATERIAL AND METHODS: [corrected] 100 patients treated in Salah Azaiez Institute from January 2005 to December 2006, who underwent surgical biopsy for breast microcalcifications The diagnosis was based on mammography associated in 60% of the cases, to ultra-sonography. We correlated biopsies results to ACR classification. RESULTS: 123 surgical biopsies are related to ACR 3 lesions in 72 cases (58.5%) ACR 4 in 39 cases (32%) and ACR 5 in 14 case (11.5%). The histological examination showed malignant lesions in 4 cas/72 ACR3 (5.5%), 19/39 ACR4 (48.7%) and 10 among the ACR5 (71.4%). CONCLUSION: Our preliminary study introduces a diagnostic approach of mammary microcalcifications, that are usually infra-clinic lesions, in a general context of breast tumors detected with an average size of more than 3 cm.

[Sarcomatoid carcinomas of the upper airways]. / Carcinomes sarcomatoïdes des voies aéro-digestives supérieures.

INTRODUCTION: The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges. MATERIAL AND METHOD: We report 11 cases of spindle cell carcinomas of the upper airways. RESULTS: Sex-ratio was 10:1 and the mean age was 57.3 years (30 - 75 years). Nine patients were smokers and 4 presented with a history of radiation exposure. Tumoral locations were as follows: larynx: 6, hypopharynx: 1, oropharynx: 1, nasopharynx: 1, oral cavity: 2. Histological diagnosis in 3 cases required the use of immunohistochemical studies. Four patients were first seen at an advanced stage. This left 9 patients and among them 7 received a curative treatment: 5 by surgery alone, 1 by surgery and radiotherapy, 1 by radiotherapy, 1 by chemo-radiotherapy for the nasopharyngeal lesion and 1 by chemotherapy alone. Two patients died from their disease before treatment. With an average delay of 15.4 months, the rates of global survival and disease-free were 5/9 and 4/9 respectively. CONCLUSION: The sarcomatoid carcinoma of the upper airways is rare, but not unusual. Its diagnosis benefits from progresses in immunohistochemistry, but also from advances in the field of molecular biology. Its treatment and natural evolution remain controversial.

[Typical medullary carcinoma of the breast: a retrospective study about 33 cases]. / Carcinome médullaire typique du sein : étude rétrospective à propos de 33 cas.

OBJECTIVE: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. It represents less than 5% of all breast cancer. It is known for its favourable prognosis. Considering the rarity of the series we could retrieve, we aimed at underlining the particularities of this pathology. PATIENTS AND METHODS: Retrospective study about 33 cases of typical medullary carcinoma managed at the Salah-Azaïz Institute during a period of six years between 1994 and 1999. RESULTS: The mean age was 47.5 years. The left breast was concerned in about 55% of cases. Mean tumoral size was 46mm. Sixty-one percent of our patients were treated by radical surgery. Seventy-three percent undergo radiotherapy, 57% chemotherapy and 42% hormonotherapy. The five-year free-disease survival was about 85%. DISCUSSION AND CONCLUSION: Typical medullary carcinoma of the breast is a rare histological form of breast carcinoma. Its treatment is similar to the other breast cancers. Our results agree with the different published studies and confirm its favourable prognosis.

Matrix-producing breast carcinoma: a case report of this rare entity.

Matrix-producing carcinoma of the breast is very rare with few cases reported in the literature. This entity is characterized by the association of malignant epithelial elements and a mesenchymal component. Therapeutic strategy is not well established and prognostic factors need further research. We report here a case of matrix-producing carcinoma in a 46-years-old woman who presented with a large lump in her left breast. A core biopsy concluded to an invasive carcinoma but neoadjuvant chemotherapy was not helpful. Diagnosis of matrix-producing carcinoma was done on the lumpectomy specimen after excision of the fast-growing mass. Immunophenotypic profile was very suggestive showing tumoral cells positivity for cytokeratins, epithelial membran antigen and S-100 protein. One year later, the patient developed lung metastases.

[Secondary breast cancer after treatment for Hodgkin's disease. About seven cases]. / Cancer du sein secondaire après traitement pour maladie de Hodgkin. A propos de sept cas.

OBJECTIVE: Therapeutic results of Hodgkin disease (HD) have improved by the use of combined radio-chemotherapy. However, this association can increase the risk of on-term effects including secondary cancers. In a retrospective study, we collected secondary breast cancer (BC) in patients previously treated with chemoradiotherapy for Hodgkin disease at Salah-Azaïz institute of Tunis. PATIENTS AND METHODS: Between 1975 and 2003, seven patients (six women and one man) treated for HD subsequently developed BC. Mean age at diagnosis of HD was 21 years (12-29). The first treatment was combined chemotherapy (MOPP-ABVD) and radiotherapy for all patients. Radiotherapy was delivered with cobalt 60 with large fields. The median dose was 41.3 Gy (2 Gy/fraction in 6 patients and 3.3 Gy in one). RESULTS: The breast tumours occurred after a median delay of 204 months (132-276). According to the TNM classification, we showed two stage T2, one stage T3, two stage T4b and two stage T4d. The mean clinical size was 47 mm (25-80 mm). All patients had infiltrating carcinoma. Axillary node histological involvement was found in 6 cases. All patients were treated by mastectomy and chemotherapy. Only one patient had a locoregional irradiation. Median survival was 26.5 months (12-48). Four patients died and three are still alive at respectively 24, 31 and 144 months. DISCUSSION AND CONCLUSION: According to the previous data, breast cancer represents 6.3 to 9% of all second cancers occurring after HD treatment. We conclude that especially young women and girls treated for HD should be carefully monitored. We suggest that secondary BC be sometimes treated by conservative radiosurgical approach.

[Benign schwannoma of the breast: about two cases]. / Schwannome mammaire bénin: à propos de deux cas.

Schwannoma is a rare nervous tumor developed on schwan cells. Only 22 cases of breast schwannoma have been published since 2005. It usually appears as a breast lump having clinical and radiological characteristics suggestive of kindness. Its diagnosis is histological. Its treatment is surgical. Through two observations and a review of the literature we would try to remind the characteristics of this tumor.

[Mammary tuberculosis: a retrospective study of 65 cases]. / Tuberculose mammaire: étude rétrospective de 65 cas.

OBJECTIVES: Remember the clinical, morphologic and histological particularities of mammary tuberculosis. Discuss clinical and radiological diagnostic problems caused by this localization, as far as breast cancer is concerned. PATIENTS AND METHODS: This is a retrospective study concerning 65 women suffering from mammary tuberculosis, diagnosed at Salah Azaiez Institute between January 1980 and December 2001. RESULTS: In this series, mammary tuberculosis represents 0.2% of the declared tubercular localizations and 0.3% of the mammary pathologies treated at the institute. The mean age of our patients was 36 years (19 to 79). Clinical findings were misleading. In 60% of cases the aspect was of a malignant tumor, in 24.6% of cases of a benign nodule and in 16.4% of cases of an abscess. The mammography concluded to a malignant lesion in 49% of cases. The fine needle aspiration achieved at 8 patients was negative in 6 cases and brought back the caseum in the 2 others. The diagnosis has been made, for all our patients, after histological study when we found typical tuberculosis lesions on pieces of tumorectomy, or biopsy. The diagnosis of tuberculosis was established; all patients had an anti-tuberculosis medical treatment in a department of infectious diseases out of the institute. DISCUSSION AND CONCLUSION: Clinical and radiological features of mammary tuberculosis are very confusing and cause a diagnostic problem with breast cancers. In front of symptoms evoking tuberculosis, biopsies must be done to eliminate an eventual cancer.

[Pelvic pseudotumoral actinomycosis with multisegmental lumbosacral root failure. A case report]. / Actinomycose pelvienne pseudotumorale avec atteinte multiradiculaire lombosacrée. A propos d'un cas.

We report a case of pseudotumoral pelvic actinomycosis with lumbosacral spinal involvement in a 21 year-old woman. The radiological work-up showed a pseudotumoral left ovarian lesion extended to sacral spine, which involved the fifth lumbar vertebra. Diagnosis of actinomycosis was established in histopathological examination of the tubo-ovarian mass under laparotomy. After four months of treatment with ofloxacin and rifampicin evolution was marked by improvement of general health and infection, associated to a progressive recovery of motricity of the lower limbs. Early diagnosis of pelvic actinomycosis may prevent the occurrence of rare but severe neurological complications of this disease.

[Relapse of gigantomastia after mammoplasty. Report of a case and literature review]. / Récidive d'une gigantomastie après mammoplastie. A propos d'un cas et revue de la littérature.

Gigantomastia is a very rare entity of undetermined aetiology that may be due to hormonal imbalance, decreased hormonal catabolism or hypersensitivity of the target organ. It poses the problem of surgical treatment, which can be exceptionally radical of necessity. We report a case of a 32-year-old woman of whom volume and vasculocutaneous complications required a simple bilateral mastectomy to treat a recurrence of gigantomastia occurring some months after a mammoplasty. Most of the cases of gigantomastia found in the literature are associated to the pregnancy or puberty and very rare cases of spontaneous gigantomastia were listed.

[Nasopharyngeal carcinoma. Recent data]. / Les carcinomes du nasopharynx: donnée actuelles.

Nasopharyngeal carcinoma (NPC) represents an interesting model in the field of head and neck cancers. This cancer is rare in occidental countries (<1/100,000) and relatively moderate to highly frequent in the Mediterranean area and south-east Asia. This disease is linked to Epstein-Barr virus with a latent infection starting in the oropharyngeal epithelium and involving not only both epithelial tumor cells but also B lymphocytes. This viral infection represents the early phase of carcinogenesis where Latent Membrane Protein-1 has an important role via the terminal part of the BARF-1 gene. There are also various chromosomal alterations reported in NPC concerning the regions of chromosomes 3p, 9p, 11q, 13q, 14q et 16q detected essentially in areas of suppressors genes. Allelic and antigenic specificities of class II and II HLA seems to be associated to an increased risk of NPC different according to the incidence areas. Anti-EBV serology is suggestive of for NPC with an elevated level of IgA EA (early antigen) and VCA (viral capsid antigen). Cyfra 21 represents a promising serum marker for NPC with a 80% sensitivity. Radiotherapy remains the base of loco-regional treatment with a more frequent and systematic use of systemic chemotherapy (primary or concomitant) for high-risk-patients (T3-4 and N2-3 disease).