Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa.

BACKGROUND: Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations. METHODS: To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia. RESULTS: Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1. CONCLUSIONS: Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa.

BACKGROUND: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.  METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.  RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Cancer in Moroccan elderly: the first multicenter transverse study exploring the sociodemographic characteristics, clinical profile and quality of life of elderly Moroccan cancer patients.

BACKGROUND: Moroccan incidence of cancer is increasing with the lengthening of life expectancy. Data regarding elderly Moroccan cancer patients are lacking. In the context of our project aiming to develop an adapted version of the Comprehensive Geriatric Assessment CGA to the Moroccan population, we launched the first Moroccan multicenter transverse study to explore the characteristics of elderly Moroccan cancer patients. METHODS: The study was conducted in nine Moroccan medical oncology departments. Patients were enrolled over 4 months. Inclusion criteria were patients aged 65 years or over with verified solid cancer. The questionnaire included four sections: socio-demographic and economic data, clinical data, vulnerability and EORTC-QLQ C30. We explored the entire included population. Then, we compared the results according to age (65-70 years old and ≥ 71 years old) and sex. We also explored the correlation between G8 scores and the ability to practice religion as an indicator of fitness level. RESULTS: In total, 164 patients were enrolled. The mean age was 73.18 ± 6.01 years. The majority of patients were married, lived with their children and received their financial income from them. Fifteen percent of families asked to hide the diagnosis from the patient. Breast (23%), colorectal (15.9%) and lung (14%) cancers were the most frequent, and 83.5% had an abnormal G8. The majority of the patients were independent for basic daily activities. Female patients had poorer social and economic conditions. Abnormal G8 was correlated with religious practice and quality of life scores. CONCLUSION: This is the first multicenter prospective study designed to collect data on the lifestyle and clinical profiles of elderly Moroccan cancer patients as an Arab and Muslim population. Our study shows that it is a well-cared-for population with strong social ties. However, there is deep economic vulnerability, especially among women, requiring urgent care. Religious practice is an important daily activity for our elderly patients and should be included in the Moroccan CGA.

Intestinal intussusception in a young women: unusual cause and specific management.

BACKGROUND: Intussusception in adults is a rare cause of abdominal pain that is often associated with organic pathology. We describe a case of ileocolic intussusception revealing a cecal adenocarcinoma in a young woman successfully managed by laparoscopic-assisted surgery adhering to oncological principles. CASE PRESENTATION: A 30-year-old woman with a family history of colon adenocarcinoma in a young brother presented to our emergency department with a 2-month history of intermittent colicky abdominal pain accompanied by nausea and vomiting. Physical examination showed a palpable mass in the right lower quadrant of the abdomen. Computed tomography showed a 3-layered structure giving the characteristic target-shaped appearance in the ascending colon, highly suggestive for an ileocolic intussusception associated with right colic parietal thickening and an adjacent lymphadenopathy. Patient was planned for laparoscopic exploration and eventually definitive surgery. Intra-operatively, we found an ileocolic intussusception with thickening of the colic wall and slight proximal intestinal dilation. Multiple lymphadenopathies along the ileocecal artery were observed. Laparoscopic right hemicolectomy was performed following strict oncologic principles with "en bloc resection" and lymphadenectomy given the risk of an underlying malignancy. Considering this risk, previous reduction of the invaginated segments was not attempted and primary extracorporeal anastomosis was performed using manual sutures. Macroscopic examination of the resected specimen revealed a tumor mass of the caecal wall .The histological analysis identified a moderately differentiated tubular adenocarcinoma invading the serosa (T3) without permeation of the lymphatic or venous capillaries. No lymphatic metastasis of 28 nodes removed was seen. Postoperative course was uneventful and patient was discharged 5 days after surgery. Postoperative chest, abdomen, and pelvis CT scan were normal. Therefore, tumor is classified as stage II A (T3N0 M0).There was loss of MLH2 and MSH6 protein expression on immunohistochemistry findings reflecting a microsatellite instability phenotype, and the patient was followed up without adjuvant chemotherapy. CONCLUSION: Ileocolic intussusception rarely revealed a cancer in young adults. Laparoscopic surgery has a special interest in the diagnosis and treatment in this pathology. Oncogenetic consultation should be required in malignant lesion.

Tumor-Stroma Ratio in ER+/HER2- Breast Cancer: Is it a Tool for Treatment Decision?

PURPOSE: The primary aim of this study is to determine the relationship between tumor-stroma ratio (TSR) and traditional prognostic factors in luminal early breast cancer in women treated at the medical oncology department of the military hospital of Rabat in Morocco. METHODS: A retrospective study was performed on primary invasive ER+/HER2- breast cancer in the period from January 1st, 2019 to December 31st, 2019. Prognostic factors included age, tumour size, lymph nodes status, Scarff-Bloom-Richardson grading, lymphovascular invasion (LVI), Ki67 and the stage of the disease. The type of Adjuvant systemic therapy was also reported .Two independent pathologists have assessed TSR by microscopic evaluation of haematoxylin and eosin tumor slides .Patients with less than 50% stroma were classified as low-stroma, the others are classified as high-stroma. RESULTS: Of 53 ER+/HER2- operable breast cancer, 41.5% patients had low-stroma and 58.5% patients had high stroma-tumour. High stroma was significantly associated with more stage III (p=0.041), more LVI (0.034), high Ki-67 (p=0.002) and more luminal B disease (p=0.001). Also, high stroma received more adjuvant chemotherapy (p=0.005). The results are maintained in univariate analysis. CONCLUSIONS: Data suggest that TSR can be used to guide decisions on adjuvant systemic therapy for ER+/HER2- breast cancer. The integration in routine of this simple and reproducible parameter requires a homogenization of the techniques as well as a prospective validation.

Breast cancer treatment and sexual dysfunction: Moroccan women's perception.

BACKGROUND: This exploratory prospective study evaluated women's responses to questions that asked them to describe how their body image and sexual functioning had changed since their breast cancer diagnosis to treatment. METHODS: A questionnaire concerning body image scale and various sexual problems experienced after diagnosis and treatment was anonymously completed by 120 women in the outpatient clinic of our hospital's Division of medical Oncology. To be eligible, subjects had to be sexually active and had histology proven breast cancer. They also had to have received treatment for breast cancer. RESULTS: 100% of participants have never spoken with their doctor about this subject. 84% of the participants continued sexual activity after treatment, but there was an increase in the incidence of sexual functioning problems which resulted in a slight reduction in the quality of their sex lives. 65% of the women experienced dyspareunia followed by lubrication difficulties (54%) and the absence or reduction of sexual desire (48% and 64%, respectively) while, 37% had lack of satisfaction (37%). Female orgasmic disorder and brief intercourse and arousal were reported respectively by 40% and 38% of the subjects. The sexual dysfunctions were absent before diagnosis and management of breast cancer in 91.5% subjects and of these 100% subjects complained of a deterioration of the symptomatology after the various treatments. 90% of the dysfunctions were observed after chemotherapy, 9% after surgery and 3% after radiotherapy; none of the subjects indicated the onset of dysfunctions to have been associated with hormonotherapy. 100% expressed not having received sufficient information about how the disease and treatment (including surgery) might affect their sexual life. CONCLUSION: Breast cancer and its treatment may result in significant difficulties with sexual functioning and sexual life. Addressing these problems is essential to improve the quality of life of Moroccan women with breast cancer.

Diagnostic challenge for ovarian malignant melanoma in premenopausal women: primary or metastatic?

BACKGROUND: In the ovary, metastatic malignant melanoma may be confused with primary malignant melanoma and presents a diagnosis challenge. Most cases are associated with disseminated diseases and poor prognosis. We present this case report of a metastatic ovarian malignant melanoma simulating primary ovarian cancer. CASE REPORT: A 45-year-old premenopausal woman was incidentally found to have an abdominal mass, 3 years after removal of a cutaneous melanoma lesion. Ultrasound and CT scan revealed left two solid masses, which were found to be an ovarian tumor at laparotomy. Left oophorectomy was performed. Histopathology and immunohistochemistry showed melanoma metastasis to the ovary. Nine months later, the patient developed epilepsy and confusion. Magnetic Resonance Imaging showed unique Wright frontal lobe lesion. She underwent stereotactic radio surgery and dacarbazine monotherapy. For months later, the patient is died from disseminate disease progression. CONCLUSION: Ovarian metastasis is an unusual presentation of cutaneous melanoma and the prognosis was dismal. As illustrated by this case report, a differential diagnosis of a metastatic malignant melanoma must be considered.

Identification of a novel pathogenic variant in PALB2 and BARD1 genes by a multigene sequencing panel in triple negative breast cancer in Morocco.

Pathogenic variants (PVs) in BRCA genes have been mainly associated with an increasing risk of triple negative breast cancer (TNBC). The contribution of PVs in non-BRCA genes to TNBC seems likely since the processing of homologous recombination repair of double-strand DNA breaks involves several genes. Here, we investigate the susceptibility of genetic variation of the BRCA and non-BRCA genes in 30 early-onset Moroccan women with TNBC. Methods: Targeted capture-based next generation sequencing (NGS) method was performed with a multigene panel testing (MGPT) for variant screening. Panel sequencing was performed with genes involved in hereditary predisposition to cancer and candidate genes whose involvement remains unclear using Illumina MiSeq platform. Interpretation was conducted by following the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) criteria. Results: PVs were identified in 20% (6/30) of patients with TNBC. Of these, 16.7% (5/30) carried a BRCA PV [10% (3/30) in BRCA1, 6.7% (2/30) in BRCA2] and 6.6% (2/30) carried a non-BRCA PV. The identified PVs in BRCA genes (BRCA1 c.798_799delTT, BRCA1 c.3279delC, BRCA2 c.1310_1313del, and BRCA2 c.1658T>G) have been reported before and were classified as pathogenic. The identified founder PVs BRCA1 c.798_799del and BRCA2 c.1310_1313delAAGA represented 10% (3/30). Our MGPT allowed identification of several sequence variations in most investigated genes, among which we found novel truncating variations in PALB2 and BARD1 genes. The PALB2 c.3290dup and BARD1 c.1333G>T variants are classified as pathogenic. We also identified 42 variants of unknown/uncertain significance (VUS) in 70% (21/30) of patients with TNBC, including 50% (21/42) missense variants. The highest VUS rate was observed in ATM (13%, 4/30). Additionally, 35.7% (15/42) variants initially well-known as benign, likely benign or conflicting interpretations of pathogenicity have been reclassified as VUS according to ACMG-AMP. Conclusions: PALB2 and BARD1 along with BRCA genetic screening could be helpful for a larger proportion of early-onset TNBC in Morocco.

Symptomatic hypopituitarism revealing primary suprasellar lymphoma.

BACKGROUND: The most common cause of hypopituitarism is pituitary adenoma. However, in the case of suprasellar masses different etiologies are possible. We report an unusual case of primary suprasellar lymphoma presented with hypopituitarism. CASE PRESENTATION: A 26 year old woman presented with amenorrhea, galactorrhea and neurological disorders. Also, the laboratory work-up revealed partial hypopituitarism. The magnetic resonance imaging of the head showed a suprasellar mass. A presumptive diagnosis of granulomatous processes was made and the patient was given steroid therapy. Repeated brain MRI detected new lesions in the brain with regression of the suprasellar mass. Stereotactic biopsy of the paraventricular lesion revealed the diagnosis of B-cell lymphoma. CONCLUSION: This case presentation reports a rare cause of hypopituitarism. Primary suprasellar lymphoma is extremely rare and represented a real diagnostic challenge. Besides, suprasellar masses are varied in aetiology and can present diagnostic problems for a radiologist. Also, because of the increased incidence of PCNSL, lymphoma must be kept in mind in the differential diagnosis of lesions in the suprasellar region.

A Long Survival Woman with Primary Small-Cell Carcinoma of the Gallbladder: Role of Chemotherapy Maintenance.

Gallbladder small-cell carcinoma (SCC) is an extremely rare cancer characterized by early metastases and associated with poor survival outcomes. The therapeutic options are limited in this indication and dedicated prospective trials are difficult to achieve. Maintenance chemotherapy is an evolving concept in medical oncology whose goal is to prolong chemotherapy-induced response. The role of maintenance therapy has been demonstrated especially in many cancers but the results remain controversial in small cell cancer. We report a case of a 49-year-old woman admitted in our institution with biliary colic, postprandial bilious vomiting, right hypochondrial mass, and deteriorated general condition. Abdominal computed tomography (CT) revealed a mass of the gallbladder with lymphadenopathy in the hepatic hilum and multiple liver metastases. CT-guided biopsy was performed that showed small, round cells with high nuclear-to-cytoplasmic ratio, and frequent atypical mitosis, which is consistent with high-grade small cell neuroendocrine carcinoma. Tumor cells were positive for chromogranin A, synaptophysin, and CD56. Ki-67 shows a high proliferation rate with 90% tumor cell staining and the diagnosis of gallbladder SCC was confirmed. The treatment used a combination of carboplatin and etoposide, interrupted by the generalized discomfort and shortness of breath during the second course of the etoposide. Repeated CT scan showed a partial radiological response in the order of 35% and carboplatin monotherapy was maintained with good tolerance and stability of the disease until the 11th cure. Thrombocytopenia at 70,000 per mm3 appeared, and its persistence forced the cessation of this treatment. Five months later, the disease progressed and second-line chemotherapy by irinotecan was given weekly. The death occurred 18 months after initiation of medical treatment due to hepatocellular insufficiency. Maintenance therapy in SCC should be considered as a promising therapeutic option when it is well tolerated.

Successful management of synchronous recurrent breast carcinoma with chronic myelogenous leukemia: a case report.

BACKGROUND: Survival is increasing after early breast cancer revealing frequent relapses and possibility of developing secondary malignancies. The concomitant occurrence of these two events is exceptionally disastrous and lethal. We report a case of a Moroccan woman who was successfully managed for synchronous recurrent breast carcinoma and chronic myelogenous leukemia. CASE PRESENTATION: A 42-year-old Moroccan woman was diagnosed with localized breast carcinoma in 2008. She received six cycles of an adjuvant chemotherapy regimen, radiation therapy and hormonal therapy by tamoxifen. After completion of 5 years of tamoxifen our patient reported asthenia; a physical examination found hepatomegaly, massive splenomegaly measuring 21 cm and supraclavicular lymphadenopathy. The staging showed lung and liver metastases. Morphology and immunohistochemical profile of this metastasis identified an adenocarcinoma of mammary origin. In parallel, the diagnosis of chronic myeloid leukemia was suspected because of the presence of a leukocytosis at 355 × 109/L, with circulating blasts of 4%. Chronic myeloid leukemia was confirmed by a bone marrow biopsy with the presence of Ph chromosome on cytogenetical analysis. Daily imatinib was ordered concurrently with chemotherapy-type docetaxel. The metastases were stable after nine courses of chemotherapy. Due to breast cancer progression 4 months later, bevacizumab and capecitabine were introduced. A major molecular response was achieved after 12 and 18 months. She has now completed 2 years of follow-up, still on a major molecular response, and is undergoing imatinib and capecitabine treatment. CONCLUSIONS: Leukocytosis in breast cancer patients can reveal chronic myeloid leukemia. It may warrant a workup to find the underlying etiology, which could include a secondary hematological malignancy.

Toxicities of docetaxel: original drug versus generics-a comparative study about 81 cases.

INTRODUCTION: Docetaxel is a chemotherapy drug widely prescribed in oncology that recognizes a variety of manufactured generics whose toxicity is increasingly reported. The aim of this study was to compare the toxicities between the original and a generics docetaxel in a Moroccan center. METHODS: In a cross sectional study, we enrolled patients treated with docetaxel from the oncology department of the military hospital of Rabat over a period of 2 years (2013-2014). We compared the prevalence of hypersensitivity reactions, febrile neutropenia, peripheral neuropathy, gastrointestinal, cutaneous, and hematologic toxicities, between four different presentations of docetaxel including the original drug. Only grade II or worse adverse events related to chemotherapy were considered. Treatments discontinuations due to toxicity were also compared. Unusual skin toxicities were included. RESULTS: 81 patients were eligible for analysis [43/generics arm vs. 38/original drug arm. Hematological toxicity was significantly more frequent in the generic arm than in the original drug (32.6 vs. 13.2 %; p = 0.04)]. Also, a signifying higher rate of treatment discontinuation was observed in the generic arm (39.5 vs. 7.9 %, p = 0.001). The use of specific generic increase numerically the skin toxicities (17.6 vs. 0 %, p = 0.026). CONCLUSION: Our data suggest that generics of docetaxel are associated with an increase of hematological and cutaneous toxicities, an increase of treatment discontinuation rate and emphasize the need of a regulation of generics' manufacture.

The Practice of Medical Oncology in Morocco: The National Study of the Moroccan Group of Trialist in Medical Oncology (EVA-Onco).

Objective. To determine the current shortfall of medical oncologists (MOs) and the projected supply. Background. Morocco, the medical oncology (MO) is a relatively new specialty. Medical oncology was recognized as a separate specialty in 1994 but the real taking-off was done only since the 2000s after the creation of the chair of medical oncology in the University of Rabat. The GRIOMM (Moroccan group of trialist in medical oncology) was created in 2011 and conducted its first study, EVA-onco, concerning the practice of medical oncology in Morocco in 2011. Design. EVA-onco is a prospective study concerning the practice of medical oncology in Morocco in 2011. Results. The entire public cancer centers completed the survey. There were no missing data. The number of medical oncologist per 100000/habitants in Morocco was 0.09. The average number of new patients seen per medical oncologist was 718 patients (ranging by state from 97 to 1875). The shortfall of MOs was estimated at 26 at least in 2011 according to the national recommendations. Conclusions. Since 2010, a national strategy to increase the capacity of MO workforce existed. The current shortfall of MO is expected to disappear in the future.

Management of stage one and two-E gastric large B-cell lymphoma: chemotherapy alone or surgery followed by chemotherapy?

UNLABELLED: Management of localized primary gastric B lymphoma (PGL) remains controversial. The aim of this study is to compare two treatments: chemotherapy alone and surgery plus chemotherapy. MATERIALS: Records of all patients with a diagnosis of gastric lymphoma and which were treated in the National Institute of Oncology, between 1999 and 2006, were reviewed and patients fulfilling the following criteria were included in this study: histologically proven large-cell B lymphoma of the stomach; complete clinical information stage I/II disease according to the Musshoff staging; patients who received surgery followed by chemotherapy (group I) or chemotherapy alone (group II). RESULTS: This study included 82 patients who were treated for cancer in our Institute. All clinical and pathological features were similar between the two groups, except that patients of group-I had significantly more stage II disease (P = 0.023) than that of group II. Among the 52 patients who could be evaluated for response to chemotherapy, there were 45 who had complete response to treatment, 3 had partial response to the treatment and 4 had progressive disease. The projected 5-year relapse-free survival (RFS) and overall survival (OS) of group I were 86.69% (95% CI, 57.9 - 97.7%) and 90.0% (95% CI, 58.0 - 97.8%), respectively. And the projected 5-year relapse-free survival RFS and OS of group II were 86.67% (95% CI, 57.0 - 88.2%) and 93.33% (95% CI, 73.3 - 98.7%) respectively. There were no statistically significant differences in RFS (P = 0.485) and OS (P = 0.551) between the two groups. CONCLUSION: Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials.

Primary lymphoma of the head and neck: two case reports and review of the literature.

BACKGROUND: The head and neck is the second most common region for the extra-nodal lymphomas after that of gastrointestinal tract. Approximately 2.5% of malignant lymphoma arises in the oral and para-oral region. In this paper we report two cases of early stage head and neck lymphoma which were managed successfully with chemotherapy and a review of the related literature. CASES PRESENTATION: The first case concerns a 48 years male patient having a diffuse large B-Cell lymphoma of the oropharynx at early bulky stage. This patient was managed successfully with 7 of Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2 d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2 d1-5 (RCHOP) regimen. The second case concerns a 50 years female patient having the nasal natural killer (NK)/T-cell lymphoma of the left nasal pit at early stage. This case was managed successfully with 6 of Cyclophosphamide 750 mg/m2 d1, Doxorubicine 50 mg/m2 d1, Vincristine 1.4 mg/m2 d1, and prednisone 50 mg/m2 d1-5 (CHOP) regimen. CONCLUSION: These two cases highlight the important role of CHOP based chemotherapy for achieving successful treatment cure for patients having an early stage head and neck lymphoma.

Carcinomatosis meníngea en el cáncer de mama: del diagnóstico al tratamiento / Meningeal carcinomatosis in breast cancer: from diagnosis to treatment

La aparición de carcinomatosis meníngea en el cáncer de mama es un suceso cada vez más comunicado en la bibliografía. Parece relacionarse con el alargamiento de la vida de las pacientes, la mejor sensibilidad al diagnóstico por imagen y la impermeabilidad de la barrera hematoencefálica a los agentes quimioterápicos. Es una forma evolutiva que afirma la invasión metastásica del espacio subaracnoideo y se correlaciona con una supervivencia limitada. El diagnóstico es difícil, debido a la inespecificidad de los signos clínicos dominados por cefaleas, trastornos cognitivos, y posibles síntomas y signos de lesiones focales progresivas. La resonancia magnética del cerebro y de la médula espinal interpretada por un especialista en neurooncología es el examen de elección en esta indicación, en búsqueda de un incremento en la captación meníngea. El análisis biológico del líquido cefalorraquídeo es un elemento esencial en el diagnóstico. Además del estudio bioquímico, la presencia de células neoplásicas es por sí sola suficiente para confirmar el diagnóstico. El número de falsos negativos es muy común y representa un gran problema diagnóstico que requiere una repetición de las punciones lumbares. Los métodos terapéuticos son estándares, a menudo invasivos, dominados por la quimioterapia intratecal y se basan sobre una evidencia científica de bajo nivel. Se analiza la epidemiología, los factores pronósticos, las herramientas diagnósticas, los tratamientos disponibles en la actualidad y las posibles terapias futuras de la carcinomatosis meníngea en el cáncer de mama (AU)

The appearance of meningeal carcinomatosis in breast cancer is an event that is being reported increasingly more frequently in the literature. It seems to be related with the lengthening of the patients’ lives, improved sensitivity to diagnostic imaging and impermeability of the blood-brain barrier to the chemotherapeutic agents. It is an evolutionary form that affirms the metastatic invasion of the subarachnoidal space and is correlated with limited survival. Its diagnosis is difficult, due to the lack of specificity of the clinical signs dominated by headaches, cognitive disorders and possible signs and symptoms of progressive focal lesions. Magnetic resonance imaging of the brain and the spinal cord interpreted by a specialist in neuro-oncology is the preferred examination in this indication, in the search for an increase in meningeal enhancement. Biological analysis of the cerebrospinal fluid is an essential element in the diagnosis. In addition to the biochemical study, the presence of neoplastic cells is in itself enough to confirm the diagnosis. False negatives are very common and represent an important diagnostic problem that entails the need to repeat the lumbar punctures. The therapeutic methods are standard, often invasive, dominated by intrathecal chemotherapy and are based on low-level scientific evidence. This study analyses the epidemiology, the prognostic factors, the diagnostic tools, currently available treatments and the possible future therapies of meningeal carcinomatosis in breast cancer (AU)