Hemophagocytic Lymphohistiocytosis: A Rare Complication of an Ultrarare Lysosomal Storage Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory condition that may be triggered by infections, autoimmune and immunologic disorders, malignancies, and metabolic diseases. Early and accurate diagnosis of HLH and its underlying cause is of paramount importance for proper management and prognosis. We report the case of a Tunisian 21-month-old girl who initially presented clinical features of HLH related to a lysosomal acid lipase deficiency. The genetic sequence analysis of the LIPA gene revealed a never described homozygous mutation c.966G>C (p.Gln322His). The parents were heterozygous for this mutation. Enzyme replacement therapy was not provided for the patient. She received etoposide, corticosteroids, and cyclosporine for the HLH. She is waiting for hematopoietic stem cell transplantation. To the best of our knowledge, this is the second Tunisian case of secondary HLH complicating lysosomal acid lipase deficiency related to a new homozygous mutation: c.966G>C (p.Gln322His).

Prognostic significance of E-cadherin and Cox 2 expression in Tunisian patients with colorectal mucinous adenocarcinoma.

INTRODUCTION: Mucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC. MATERIALS AND METHOD: A total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS). RESULTS: A reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16). CONCLUSION: Our findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.

Overexpression of miR-10b in colorectal cancer patients: Correlation with TWIST-1 and E-cadherin expression.

MicroRNAs are emergent players of epigenetics that function as oncogenes or tumor suppressors and that have been implicated in regulating diverse cellular pathways. MiR-10b is an oncogenic microRNA involved in tumor invasion and metastasis in various cancers. Our data have shown that miR-10b is overexpressed in colorectal cancer samples in comparison with non-tumorous adjacent mucosa (p = 0.0025) and that it is associated with severe features such as tumor size >5 cm (p = 0.023), distant metastasis (p = 0.0022), non-differentiated tumors (p = 0.016), and vascular invasion (p = 0.01). Regarding the regulation of its expression, positive correlation between the loss of miR-10b and aberrant DNA methylation (p = 0.02) as well as a loss of TWIST-1 messenger RNA (p = 0.018) have been observed. Furthermore, expression analysis of the downstream miR-10b targets has shown that there are associations between low HOXD10 messenger RNA and E-cadherin protein levels (p < 0.0001, p = 0.0008, respectively) and overexpression of miR-10b. Our data suggests that overexpression of miR-10b results from high levels of TWIST-1 and may induce a decrease of E-cadherin membranous protein levels, thus contributing to the acquisition of metastatic phenotypes in colorectal cancer.

[Tubulo-papillary apocrine adenoma in association with syringocystadenoma papilliferum]. / Adénome tubulo-papillaire apocrine associé à un syringocystadénome papillifère.

Tubulo-papillary apocrine adenoma (TAA) is a very rare sweat gland tumor. TAA in association with syringocystadenoma papilliferum (SCP) is exceptional. A 2-year-old Tunisian child developed a mixed tumor on the scalp: TAA in association with SCP. Histologically, the tumor consisted of dilated duct-like areas with some apocrine gland-like areas. The superficial part of the tumor was connected to the epidermis and showed the characteristics of SCP. The characteristics and differences in histopathologic and immunohistochemical findings in this mixed tumor are described.

A spindle cell myoepithelioma of parotid gland : a case report.

BACKGROUND: Myoepthelioma is a rare salivary gland tumor which is usually located in parotid gland and in minor salivary glands. CASE REPORT: We report a case of myoepithelioma arising in an accessory paritid gland in a 47-yearold woman who presented with a slowly expanding subcutaneous nodule on the left cheek, that was within the parotid gland at surgical resection . This tumor was composed of spindle cells. Immunophenotypical characterization demonstrated its myoepithelial nature. CONCLUSION: In the subcutaneous tissue, this unusual neoplasm may be confused with soft tissue tumors showing spindle cell features.

[Mixed breast carcinoma with melanocytic differentiation in a man]. / Carcinome mammaire mixte avec différenciation mélanocytaire chez un homme.

INTRODUCTION: Male breast cancer is rare; the lobular type is exceptional. Only one case of mixed ductal and lobular type is reported in the literature. This is the first report on a mixed ductal and lobular carcinoma with melanocytic differentiation in a man. The aim of our study is to describe the clinicopathological characteristics of this rare type of breast tumor and to discuss its histogenesis. CASE REPORT: A 63-year-old man presented with cutaneous ulceration of the left breast. Ultrasound of the breast revealed a solid hypoechoic lesion, 13 mm in diameter. Microscopic evaluation of the biopsy showed an invasive ductal carcinoma. The patient received three cycles of chemotherapy and lost of view. Then consulted for increasing of the tumor size reaching 3 cm. Histological examination of the mastectomy specimen showed a mixed ductal and lobular carcinoma with melanocytic differentiation, confirmed by the immunohistochemical study. The patient received adjuvant chemotherapy and the evolution was favorable with an average follow-up of 9 months. CONCLUSION: Breast carcinoma with melanocytic differentiation is extremely rare; only seven cases are reported in the literature and all occurs in females. Its histogenesis is unclear; tumors exhibiting this combination of cell types may occur as collision or composite tumors.

Comparative study of the effect of oleuropein and hydroxytyrosol rich extracts on the reproductive toxicity induced by bisphenol A in male rats: biochemical, histopathological, and molecular analyses.

Bisphenol A, or BPA, goes into the composition of a large number of products including sunglasses, infant's feeding bottles, receipts, or food packaging. Nowadays, there is a growing evidence that BPA may be at the origin of several physiological malignancies. Oleuropein and hydroxytyrosol extracted from olive leaves are highly investigated for numerous health benefits. The present work investigates the potential protective proprieties of olive leaf extracts against BPA-induced testicular damage in Wistar rats. Thirty-two animals were randomly divided into 4 groups: control, BPA-treated (10 mg/kg), BPA and oleuropein rich extract (16 mg/kg) treatment, and the last group treated with BPA and hydroxytyrosol rich extract (16 mg/kg). Biochemical parameters and histological and molecular analyses were evaluated. Our data demonstrated that BPA treatment caused significant alteration in biochemical parameters, disorganization of germinal epithelium, an up-regulation of p53 and Bax, and a reduction of Bcl-2 protein levels. The ingestion of oleuropein- and hydroxytyrosol-rich extracts attenuated BPA-induced biochemical and histological changes. In fact, olive leaf extracts enhanced the enzymatic antioxidant system and the level of Bcl-2, and reduced the expression of p53 and Bax. Fairly, our findings propose that olive leaf extracts may compete with BPA-induced reprotoxicity in vivo.

Slow-growing pedunculated nodule.

There have been limited reported cases of pedunculated basal cell carcinoma(BCC). Our case is original, and it combines two rare aspects of CBC: Pedunculated and giant. This uncommon aspect is rarely encountered.

Papillary thyroid carcinoma associated with glioblastoma in a neurofibromatosis 1 patient: An unusual and rare combination of multiple primary malignancies.

Introduction: and importance: Papillary Thyroid carcinoma (PTC) is the most common endocrine malignancy and accounts for 1-2% of all cancer cases. Second malignancies in women diagnosed with thyroid cancer are of concern given the young average age at diagnosis. The concurrent occurrence of thyroid cancer and malignant brain tumor such as glioblastoma (GBM) was rarely seen and reported. However, the simultaneous association of these 2 conditions, namely PTC and GBM, in a neurofibromatosis type 1 (NF1) patient, has never been reported before in the literature. Case presentation: The authors report the first case of an extremely rare association combining papillary thyroid carcinoma, glioblastoma, and a neurofibromatosis 1 in a 34-year-old female patient with primary generalized tonic-clonic seizures. Clinical discussion: NF1 can be associated with PTC and GBM independently. In this current case, NF1 was accompanied by both PTC and GBM. With the exception of the present case, to our knowledge, there has been no previous case report in the literature in which these 3 entities were associated. The reason for the rarity of this combination of these neoplasms in patients with NF1 remains not clear, but it may be explained by the low incidence of combined occurrence of PTC and GBM. Conclusion: This is the first reported extremely rare coexistence of GBM and PTC in a female NF1 patient. Further genetic investigations could improve our understanding of this combination and change our therapeutic approaches.

[Abrikosoff's tumor: a clinicopathologic study of nine cases]. / Tumeur d'Abrikosoff : etude anatomoclinique de neuf cas.

BACKGROUND: Abrikossoff's tumour or granular cell tumor or is a benign neurogenic tumour. It is ubiquitous with the most frequently affected site is the head and neck region. AIMS: To report a series of granular cell tumors and to discuss its clinicopathologic features and histogenesis. METHODS: We report a series of nine cases diagnosed between January 2004 and December 2006 in the Pathology Department of the University Hospital of Sfax. We have collected the clinical aspects and we have proceeded on a pathological, cytochemical (PAS and PAS diastasis) and immunohistochemical study. RESULTS: Nine cases of TCG are presented: 5 females and 4 males. The median age was 33.9 years (extremes: 7 and 53 years). All tumours were unique. The most common localization was in the head and neck region (5 cases). The diagnosis was suspected using standard histologic criteria and confirmed by immunohistochemistry: tumour cells expressed vimentine (90%), S100 protein (100%) and neuron specifique enolase (80%). In all cases patients were treated by excisional resection and had a benign course with no evidence of recurrence (median follow up: 2 years). CONCLUSION: Granular cell tumours are rare neoplasm which must be recognised because they demonstrate a benign behaviour after their surgical excision. Histological features of granular cell tumours are commonly characteristic but some times they can be misdiagnosed as malignant tumours especially when the biopsy is superficial. The staining for neurogen markers and PAS are useful tools.

Prognostic Value of Natural Killer Cells Besides Tumor-Infiltrating Lymphocytes in Breast Cancer Tissues.

BACKGROUND: Each subgroup of immune cells has a different prognostic role in breast cancer; however, the prognostic impact of tumor-infiltrating natural killer cells (TINKs) is still not well established. Our aim was to assess the prognostic impact of natural killer (NK) cells in breast carcinomas. MATERIALS AND METHODS: NK cells infiltration were assessed by immunohistochemistry (IHC). Statistical analyses were performed to evaluate the correlation of NK cells with clinical-pathological features and outcome. RESULTS: CD56 IHC was realized in 126 patients. NK cells infiltration showed significant and positive association with tumor high Scarff-Bloom-Richardson (SBR) grade. NK cells were significantly associated with HER2-positive breast cancer and triple-negative breast cancer subtypes. Analyses showed significant and inverse correlation with progesterone and estrogen receptors expression status. High NK cells were significantly related to high Ki-67 labeling index. Our data showed that high NK cells infiltrate was significantly associated with tumor-infiltrating lymphocytes in breast cancer tissues. At a median follow-up of 5.5 years, high CD56 expression (≥ 5 cells/10 high power field) was associated significantly with a good overall survival and with good disease-free survival. CONCLUSION: In this study, we assessed the important prognostic role of TINKs in breast carcinomas, which seems to be evident despite its association with aggressive pathological features. Thus evaluation of NK cells can be standardized and integrated in daily routine.

Hypermethylation of RARß2 correlates with high COX-2 expression and poor prognosis in patients with colorectal carcinoma.

Silencing of gene expression by aberrant methylation at the CpG islands is common in human tumors, including colorectal cancer. This epigenetic alteration affects promoter of genes having crucial cellular functions such as tumor suppressor, DNA repair, apoptosis, cell adhesion, etc. We investigated the methylation status in the promoter regions of the RARß2, RASSF1A, DAPKinase, and CDH1 genes in 73 colorectal carcinoma and 43 paired normal tissues of Tunisian patients using methylation-specific PCR assays. The association between methylation status and the clinicopathological features was evaluated. To determine whether aberrant methylation affects gene expression, we performed immunohistochemistry analysis for E-cadherin and COX-2, a target gene of RARß2. The methylation frequencies vary from 80.8% for RARß2 to 35.6% for RASSF1A while in non-tumor-paired samples; the frequencies of methylation are significantly lower for all the fourth genes tested. The methylation status did not correlate with any of the clinical features considered; however, aberrant methylation of RARß2 was associated with a shortened overall patients' survival (p log rank = 0.026); nevertheless, it needs to be confirmed on larger sample size. Moreover, a significant inverse association was observed between methylation status of RARß2 and COX-2 protein expression in tumor specimen (p = 0.014). On the other hand, we found that loss of E-cadherin expression was significantly associated with aberrant methylation of the CDH1 promoter (p = 0.005). Our findings showed that RARß2 was frequently methylated in colorectal cancer and correlated with a worse prognosis and high expression of COX-2 suggesting a link between these two proteins in colorectal carcinogenesis. We also showed that epigenetic alteration of CDH1 is a major mechanism of the loss of E-cadherin protein expression in primary colorectal tumors.

[Cerebral gliosarcoma: clinico-pathologic study of 8 cases]. / Gliosarcome cérébral: etude clinico-pathologique de 8 cas.

BACKGROUND: Gliosarcomas are biphasic neoplasms composed of a glioblastoma admixed to a sarcomatous component with different lines of differentiation. Histogenesis of these tumors is still discussed. AIM: Our objective is to specify clinical and pathological characteristics of this rare neoplasm and to discuss its histogenesis. METHODS: Retrospective study of eight cases of gliosarcomas diagnosed between January 1998 and December 2004. Clinical, radiological, therapeutic and follow-up data were reviewed. Histological features and immunohistochemical results were also included in this review. RESULTS: Five patients were male, three women with a median age of 50.7 (range 31-74 years). Symptoms were dominated by intracranial hypertension and paralysis. The most common location was parietal or temporo-parietal (5 cases: 62.5%). Pathological exam including histochemical and immunohistochemical study confirmed the diagnosis of gliosarcoma in all cases. Sarcomatous component had features of fibrosarcoma in 5 cases, osteosarcoma in 2 cases and malignant fibrous histiocytoma in 1 case. All patients were treated by surgical excision (complete in five cases and partial in three cases). Adjuvant radiotherapy was received in three cases. One patient was lost on follow-up. Two patients died from postoperative. complications and the five remaining patients died with a medium follow up of 9 months (extremes: 2-24 months). CONCLUSION: Clinical, radiological and follow-up features of gliosarcomas share great similarities with glioblastomas. Histopathological, histochemical and immunohistochemical studies are helpful in accuracy diagnosis. Recent cytogenetic and molecular data support a monoclonal origin for these tumors.

Aggressive nasal-type natural killer/T-cell lymphoma associated with Epstein Barr virus presenting as testicular tumor.

BACKGROUND: Testicular lymphoma is a lethal disease with a median survival of approximately 12 to 24 months. Nasal-type natural killer/T-cell lymphoma of the testis is exceptional whether as a primary or secondary tumor. AIM: The authors report on the comprehensive histopathologic, immunohistochemical and molecular analysis of a case of primary testicular nasal type NK/T cell lymphoma and review the features of previously reported cases. OBSERVATION: We report a case of primary nasal-type natural killer/T-cell lymphoma of testis in a 28-year-old male. The histopathological examination of the surgical specimen, showed a large lymphoma cells with angioinvasion expressing CD3 (cytoplasmic), CD2, CD8, CD43, CD45, CD45Ro, CD56, T-cell intracellular antigen-1, perforine, Mib1 and granzyme. In situ hybridation for Epstein-Barr-virus- encoded mRNA was positive. Polymerase chain reaction study of formalin-fixed tissue showed lack of T-cell receptor gene rearrangements. The initial stage was I (EA) of Ann Arbor. This lymphoma was refractory to chemotherapy. The patient developed lymph node metastases in the out iliac and in the subclavicular region two months later. He died of disease after eight months. CONCLUSION: This study confirms that testicular NK/T-cell lymphoma deserves to be distinguished from the other testicular lymphomas. In fact, this lymphoma tends to occur at young age, to disseminate early, to have an aggressive course, and is strongly associated with EBV.

Adenoid cystic carcinoma of the parotid with facial nerve invasion.

BACKGROUND: Adenoid cystic carcinoma comprises approximately 10% of all epithelial salivary neoplasms and most frequently involves the parotid. Perineural invasion is a common feature but intraneural invasion and spread is less common. AIM: The authors report a case of parotid adenoid cystic carcinoma with invasion and spread via the facial nerve with an emphasis on radiologic features. OBSERVATION: We report a case of a 47-year-old man presenting with a right submandibular mass evolving for 4 years. On physical examination, the mass was firm painless, well delineated. There was no facial paralysis. The magnetic resonance imaging (MRI) examination showed a right parotid gland solid mass located in the deep lobe of the parotid gland with mastoid bony involvement.The mass was heterogenously enhanced. High resolution non contrast computed tomographie (CT) scan of the temporal bone showed in the axial and coronal cuts, a widening of the mastoid segment of the facial canal with involvement of the facial nerve. Pathologic examination of the resected specimen revealed histological features of adenoid cystic carcinoma with intra neural invasion of the mastoid segment of the facial nerve. The surgical margins were free. The evolution was favourable 5 years later. CONCLUSION: This study confirms that multiplanar approach of MRI allows rapid detection of adenoid cystic carcinoma. The influence of intraneural invasion and spread on survival remains controversial.

[Ewing sarcoma osseous and extraosseous : a clinicopathologic study of 29 cases]. / Sarcome d'Ewing Osseux et Extra Osseux : Etude anatomo-clinique de 29 cas.

BACKGROUND: Ewing's sarcoma (ES) is a rare tumour accounting for 10% of primary malignant bone tumours in children and 3% of all childhood malignancies. ES belongs to a group of small round cell tumours. AIM: In this review, we will describe the main clinicopathological features of this rare tumour and discuss its prognosis. METHODS: We report a retrospective study of 29 cases of ES, of which 4 were extraosseous, diagnosed over a period 11 years (January 1989 - December 1999). Clinicopathological data were described. Hematoxylin-eosin staining and immunohistochemical study were reviewed. RESULTS: 12 patients were male and 17 were female (ratio: 0,8) with a median age of 16 years. 62,5% of tumours were located in flat bone and 33,3% in long bone. The medium size of the tumor was 10,6 cm (range:3-25cm). 27,5% of patients presented with metastatic disease at time of diagnosis. Microscopically, tumour tissue was composed of round, small, blue cells with fine granular chromatin. Tumour cells strongly coexpressed CD99 and vimentin (100%). Systemic treatment consisted of adjuvant chemotherapy (84,2%). Local control was based on and surgery (57,9%) or radiation therapy (36,8%). A good response to chemotherapy was obtained in 37.5%; 13,7% of patients were alive without disease (medium follow up: 169 mois); 34,5% of patients developed metastases (medium follow up : 23 months) and 10,3% developed recurrences (medium follow up :13 months). CONCLUSION: Our study emphasizes two points : the great size of the tumor and the frequent location in flat bone which may explain the poor prognosis of Ewing sarcoma in our series despite the multidisciplinary treatment.

Gliosarcoma with osteosarcomatous features: a short illustrated review.

INTRODUCTION: Gliosarcoma is a rare, malignant, biphasic brain tumor formed by both glioblastoma and sarcomatous components. Various lines of differentiation are described in the latter component, but most commonly fibrosarcomatous and pleomorphic sarcoma are present. Osteosarcomatous features are exceedingly rare. OBJECTIVE: We report a case of gliosarcoma with osteosarcomatous features in a 33-year-old woman. METHODS: Histologically, the sarcomatous portion displayed a typical pattern of fibrosarcoma associated with areas of osteoid formation. RESULTS AND CONCLUSION: Immunohistochemical glial fibrillary acid protein (GFAP) expression was seen only in the glioblastoma portion. Clinicopathological characteristics and radiological data of this rare condition were reviewed. Possible differential diagnoses and potential histogenesis were also discussed.

[Scalp metastasis from small cell carcinoma of the rectum: an unusual case]. / Métastase au niveau du cuir chevelu d'un carcinome a petites cellules du rectum: un cas inhabituel.

BACKGROUND: Cutaneous metastasis of rectal carcinoma is a rare event. It occurs in 4% of all patients with rectal cancer. Skin metastasis of rectal cancer are usually detected near the initial tumor, especially in the periumbilical region; but they rarely occur in the scalp. AIM: To report a new case of scalp metastases from rectal tumor. CASE REPORT: Our patient was a 63-year old male with a history of small cell carcinoma of the rectum who subsequently developed a single nodule of the scalp of 4cm. Histopathological analysis revealed a small cell carcinoma infiltrating the dermis and subcutaneous tissue. The patient underwent palliative chemotherapy but his disease continued to progress. CONCLUSION: In contrast to the prior cases of scalp metastases reported in the literature, ours is the first documentation of such an occurrence from rectal small cell carcinoma. The early diagnosis of skin metastases in these patients is very important because it can alter treatment.