Massive Silent abdominal ganglioneuroma in the setting of non-Hodgkin lymphoma : A rare case report.

INTRODUCTION AND IMPORTANCE: Ganglioneuroma is a rare benign neuroblastic tumor originating from sympathetic ganglion cells in the peripheral nervous system. It is often incidentally discovered during imaging studies and primarily affects children and young adults. CASE PRESENTATION: We present a case report of a 21-year-old female diagnosed with non-Hodgkin lymphoma who had an abdominal mass incidentally detected during imaging, Initially mistaken for lymphoma in the setting of the primary diagnose. After the chemotherapy for the lymphoma, the mass did not response to the treatment, so the mass was surgically excised, and histopathological examination confirmed the diagnosis of ganglioneuroma. The patient responded well to treatment for lymphoma and remains in good condition without signs of recurrence. CLINICAL DISCUSSION: To the best of our knowledge, this is the first case that describes an association between an intraabdominal ganglioneuroma and non-Hodgkin's lymphoma. CONCLUSION: This case highlights the importance of considering ganglioneuroma as a differential diagnosis when evaluating abdominal masses in patients with lymphoma.

The clinical challenge of a uterine cotyledonoid dissecting leiomyoma with adenomyosis: A case report.

Cotyledonoid dissecting leiomyoma (CDL) is a rare uterine tumor with unique clinical and histological features. We present a case of a 46-year-old woman with a 3-month history of left-flank pain radiating to the back. The patient had a history of infertility and a previous miscarriage. Ultrasound revealed a solid tissue mass suggestive of a degenerated fibroid. Laparoscopy identified subserosal leiomyoma and leiomyoma in the broad ligament. Histologically, CDL is characterized by disorganized smooth muscle with hyaline degeneration and no evidence of malignancy. Clinically, CDL can present with a variety of symptoms, including heavy menstrual bleeding, pelvic pain, and infertility. The coexistence of CDL and adenomyosis is exceedingly rare. This case highlights the importance of considering CDL in the differential diagnosis of pelvic mass, malignant neoplasms, and infertility, even with atypical symptoms. It also emphasizes the value of cooperation between clinicians and pathologists for accurate diagnosis and management of CDL. Adenomyosis in this case further complicated the diagnosis and highlighted the need for an index of suspicion for this rare condition.

The first reported case of fibrous hamartoma of infancy in Syria: A rare case and review of literature.

INTRODUCTION AND IMPORTANCE: Fibrous hamartoma of infancy (FHI) is an anomaly in the soft tissue. It is usually benign and rare, with most cases found in children under the age of two. CASE PRESENTATION: A case is reported involving an 11-year-old boy who visited a plastic and reconstructive surgery clinic with a painless mass on his left iliac region. The mass had been there since birth and had been growing gradually in size. After obtaining informed consent, surgical exploration was conducted. Following that, the mass was completely surgically removed with appropriate dissection and layer-by-layer suturing. An excisional biopsy was sent to the pathology department for further analysis. The final diagnosis was FHI, and no signs of malignancy were found. CLINICAL DISCUSSION: According to our knowledge, this is the first documented case in medical literature in Syria describing the clinicopathologic features and follow-up results of an 11-year-old boy diagnosed with FHI. Typically, the tumor is detected within the first two years of life, but in some cases, up to 23% of cases are already present at birth. It is interesting that our case was discovered at the age of 11, due to its small size when it developed after birth, and because the patient's family believed that it would heal spontaneously as it gradually increased in size, which prompted them to come to the clinic. CONCLUSION: Misdiagnosis may lead to unnecessary consequences, such as concerns of the patient's family, and invasive procedures. Therefore, FHI should be considered in the differential of a solitary mass in infants.

A pleuropulmonary blastoma type III in a 4-month-old infant: First case report in Syria.

INTRODUCTION: Pleuropulmonary blastoma is a rare, aggressive intrathoracic neoplasm of early childhood. CASE PRESENTATION: We report a case of a 4-month-old male baby who has presented with recurrent respiratory infections since birth. A surgical team was consulted due to abnormal opacification observed on a chest X-ray. An enhanced-contrast CT scan of the chest revealed a heterogenous, well-delineated mass measuring about 3,8 × 6 cm in the posterior mediastinum. A left posterolateral thoracotomy was performed. The mass was separated from the lung parenchyma, located behind the parietal pleura, and adherent to the chest wall and superior ribs. The lesion was totally removed. Histologically, the lesion was a pleuropulmonary blastoma type III. Currently, the patient is on a 6-month course of chemotherapy. CLINICAL DISCUSSION: The aggressive, insidious behavior of PPB requires a high index of suspicion for diagnosis. The clinical manifestations and imaging modalities are atypical and nonspecific. However, PPB should be kept in mind when a huge solid or cystic mass is observed in the lung field on imaging. CONCLUSION: Extrapulmonary pleuropulmonary blastoma is a very rare entity characterized by highly aggressive behavior and a poor prognosis. Early excision of thoracic cystic lesions in children is warranted regardless of the symptoms to avoid future mishaps.

Thyroid-like follicular carcinoma of the kidney presenting in a 13-year-old female: a case report from Syria.

Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare cancer that emerged to the medical literature only a few years ago. We present here the first case of thyroid follicular carcinoma-like renal tumor from Syria. The case presented symptomatically and was managed in our surgical unit. Generally, the presenting age described for the previous cases was 19-60 (mean 39.5) with only three cases with younger ages. Here in our case, the patient is only 13 years old making this only the fourth case worldwide of TLFCK in a child. The microscopic view of the tumor showed distinct thyroid features. In addition the immunohistochemical stains played the definitive role in the diagnosis. The staining for Vimentin, and CK19 were diffusively positive. CK7 was focally positive, whereas TTf1, Thyroglobulin, WT1, CD10 and EMA were negative. It is important to consider this diagnosis to spare the patient the treatment protocol of primary thyroid cancer with metastasis.

Renal primitive neuroectodermal tumor. The first case series from Syria.

Primitive neuroectodermal tumor (PNET) mainly arises from soft tissues of the extremities such as humerus, femur, C tibia. It rarely arises from kidney; less than 200 cases have been reported in the literature. The clinical presentation and radiography findings are not specific. Here we first report two cases of renal primitive neuroectodermal tumor in Syria. the first patient was 26-year-old- female that presented to urology clinic complaining of right flank pain. Ultrasonography of the abdomen showed a large mixed heterogeneous mass in the right kidney with no hemorrhage or calcification and MSCT of abdomen and pelvis demonstrate a mixed well-demarcated heterogeneous mass measuring (74*117) mm in the right kidney right radical nephrectomy was performed. The second patient 19-year-old-male presented with left flank pain. Ultrasonography of the abdomen showed mixed large mass involving the left kidney, with unmarked border. The CT of the abdomen and pelvis demonstrating a (30*110*90) mm left renal mass and periaortic lymphadenopathy measuring (45*28) mm. The patient underwent Left radical nephrectomy with periaortic lymphadenectomy dissection. The final diagnosis for both cases was Renal PNET based on microscopic and immunohistochemistry examination. In patient with suspected renal mass in the radiographic images, the diagnosis of renal primitive neuroectodermal tumor should be kept in the mind despite its rarity. The final diagnosis is done by histopathological study in association with immunohistochemical examination.

Aggressive angiomayxoma in men: Case report and systematic review.

Introduction: Aggressive angiomyxoma is a rare benign mesenchymal tumor and occurs rarely in males. This study aimed to review all the cases of AAM in men in the English literature up to September 2020 and investigate the clinical, histochemical, and radiological characteristics of AAM and discuss the best treatment choices according to available data. Methods: A comprehensive search of the PubMed, Google Scholar, and Embase databases up to September 2020 was performed looking for reported cases of male patients with AAM. The search excluded articles in languages other than English, reported female cases, and superficial angiomyxoma cases. Results: Among the 97 patients, the mean age was 48.2 years with an incidence peak between 40 and 60 years. The sites commonly involved were the scrotum (42.3%). On ultrasound, the tumor was hypoechoic (85.7%) with a well-defined margin (100%), whereas on MRI, most cases were isointense on T1-weighted images (53.8%), and hyperintense on T2-weighted images (85.7%). Immunohistochemistry revealed that the tumor tended to be positive for vimentin (100%), CD34 (63.4%), ER (50%), and PR (53.3%) while S-100 showed 91% negativity. Wide and complete surgical excision was conducted in most cases (72%), and follow-up duration ranged from 1 month to 144 months with a recurrence rate of 11.8%. Conclusion: Although the occurrence of AAM is rare in men, consideration should be taken in the differential diagnosis of a mass in the genitourinary region. According to our review, the most decisive immunohistochemistry profile is the positivity of Vimentin and CD34 with the negativity of S-100. Although hormonal treatment is controversial, we suggest a novel algorithm for the management of aggressive angiomyxoma.

An unusual manifestation of Hand-Foot-Genital Syndrome: Embryonal Rhabdomyosarcoma - A case report.

Hand-Foot-Genital Syndrome (HFGS) is a dominantly inherited condition and one of the rarest cases encountered in clinical practice. It might be presented with a wide variety of limb malformations and urogenital defects manifestations. In this report, a unique and novel case of HFGS accompanied with Embryonal Rhabdomyosarcoma of the urinary bladder is described in a two-year-old male. The patient was admitted to the hospital in order to investigate a progressively enlarging mass in the lower abdomen. During hospitalization, oliguria was noted by resident physicians. However, hypospadias and dysmorphic abnormalities, demonstrated upon physical examination, were the cornerstone in the diagnosis of HFGS. An accurate visual examination of the abdomen showed dilated superficial veins, and abdominal rigidity appeared through palpation. Furthermore, the radiologic evaluation showed delayed ossification of carpal bones, and abdominal CT scan revealed a necrotic mass in the hypogastric region measuring 12 × 10 cm. A biopsy was performed through which the mass was confirmed as Embryonal Rhabdomyosarcoma of the urinary bladder. The kidney function follow-up showed normal results. Neoadjuvant chemotherapy was started to diminish the tumor size. However, the patient eventually passed away during the treatment phase. This report emphasizes the need for a high index of suspicion to establish early detection of Embryonal Rhabdomyosarcoma in each newborn diagnosed with Hand-Foot-Genital Syndrome (HFGS) to avoid potential fatal consequences.

Unusual case of classic testicular seminoma in a 90-year-old patient: a case report.

BACKGROUND: Seminoma is the most common subtype of testicular cancer and occurs most commonly in patients aged 30-49 years, but decreases to a very low level in men in their 60s or older. CASE PRESENTATION: A 90-year-old Syrian man with a 6-year history of an increase in size of his right scrotum, presented to the urological clinic and, on clinical examination, the findings suggested testicular tumor. After orchiectomy and histology results based on microscopic and immunohistochemical examinations, a pure seminoma was diagnosed, so we describe in this case report the second-oldest patient with classical seminoma in the medical literature. CONCLUSION: This case report has been written to focus on the probability of any type of testicular tumor occurring at any age or decade; urologists should consider seminoma as a differential diagnosis with any testicular swelling even in elderly patients.

Co-incidence of Human Papillomaviruses and Epstein-Barr Virus Is Associated With High to Intermediate Tumor Grade in Human Head and Neck Cancer in Syria.

High-risk human papillomaviruses (high-risk HPVs) have been recently reported to be co-present with Epstein-Barr virus (EBV) in different types of human cancers including head and neck (HN), where they can cooperate in the initiation and/or progression of this cancer. Accordingly, we herein explored the prevalence of high-risk HPVs and EBV in 80 HN cancer tissues from the Syrian population using polymerase chain reaction, immunohistochemistry, and tissue microarray methodologies. We report that high-risk HPVs and EBV are present in 35/80 (43.7%) and 41/80 (51.2%) of our samples, respectively, and the most frequent HPV types are 33, 16, 18, 45, 52, 58, 35, 51, and 31, in this order. More significantly, our data reveal that 25/80 (31.2%) of cancer cases are positive for high-risk HPVs as well as EBV, and their co-presence is associated with high/intermediate-grade squamous cell carcinomas. These data confirm the co-presence of high-risk HPVs and EBV in HN cancers in the Syrian population of the Middle East and demonstrate that their co-incidence is linked to a more aggressive cancer phenotype. Thus, future studies are required to confirm these data and elucidate the exact role of high-risk and EBV cooperation in human HN carcinogenesis.

A rare case of pelvic primitive neuroectodermal tumor with misleading symptoms: A case report.

Peripheral Primitive NeuroEctodermal Tumors (pPNETs) are rare highly malignant tumors; originating from the neuroectoderm. Although PNETs may arise in various locations (most commonly in the extremities), very few cases have been reported in the pelvis. There is still poor evidence about the management of these tumors in the literature. We present a rare case of pelvic PNET in a 20-year-old male. The patient presented with symptoms mimicking a lumbar disk hernia, which delayed the diagnosis. He was managed with a combination of a debulking procedure, adjuvant chemotherapy, radiotherapy; and has been in remission for 2 years upon follow-up. This case highlights the importance of diagnosing such aggressive tumors as early as possible (as prognosis may vary significantly), and the challenge in the management of PNETs due to poor evidence.

Co-Incidence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women.

Epstein-Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Human papillomaviruses-related cancers. Presence and prevention strategies in the Middle east and north African regions.

Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region.

High-Risk HPVs and Human Carcinomas in the Syrian Population.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection; persistent infection with high-risk types of HPV present a major risk factor for the initiation and progression of a variety of human carcinomas including cervical, colorectal, head, and neck (HN) as well as breast carcinomas. A huge number of studies investigated and reported the incidence of high-risk HPVs in these cancers worldwide particularly in the developed countries; therefore, two HPV prophylactic vaccines against the two most frequent high-risk HPV types (16 and 18) have been developed and used worldwide. However, there are very limited studies about the prevalence of HPVs in the developing countries especially in Africa and some states of the Middle East. In this mini review, we outline the presence of high-risk HPVs in human cervical, colorectal, HN as well as breast cancers in the Syrian population, which was recently explored for the first time by a Canadian/Syrian group.

Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population.

BACKGROUND: Colorectal cancer contributes heavily to cancer morbidity and mortality worldwide. Numerous therapies are currently in use, including monoclonal antibodies against cellular components involved in tumorigenesis such as epidermal growth factor receptors (EGFRs). Studies showed the polymorphism [R521K] GàA in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). AIM: We aimed at uncovering allele frequencies of this polymorphism among Syrian colorectal cancer patients and healthy individuals. MATERIALS AND METHODS: Forty-seven patients with colorectal cancer were included in a case-control study along with 48 healthy subjects, all native Syrians. Individuals were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were statistically analyzed to elucidate significant differences between the two groups. RESULTS: Allele frequencies were 40.4% (G/G), 57.4% (G/A) and 2.1% (A/A) in colorectal cancer patients and 41.6% (G/G), 43.7% (G/A) and 14.5% (A/A) in healthy subjects. The A/A genotype was significantly lower in colorectal cancer patients than in the control group. CONCLUSIONS: Homozygosity for the A allele is linked to reducing the risk of developing colorectal cancer in Syrian patients. The lower prevalence of (A/A) locally may predict sub-optimal rates of clinical response to Cetuximab compared with populations with higher frequencies of the A allele. Larger scale investigations are needed for a stronger conclusion.

Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria.

BACKGROUND: Catechol-O-methyltransferase (COMT) inactivates catechol estrogens by methylation and thus may play a protective role against mutations induced by estrogen metabolites. In this study we investigated the relationship between the Vall58Met polymorphism in the COMT gene and breast cancer risk in a population-based case control study in Syria. METHODS: We examined 135 breast cancer patients and 107 healthy controls in North Syria to determine the association between the functional genetic Val158Met polymorphism in the COMT gene and female breast cancer risk. RESULTS: There was no significant overall association between the COMT genotype and individual susceptibility to breast cancer. CONCLUSIONS: Our data suggest that there may be no overall association between the COMT genotype and breast cancer.

Does the Syrian population have to wait for the new generation of human papillomaviruses vaccine?

We recently conducted several studies regarding the presence of high-risk HPVs in human cervical, colorectal and breast cancers in the Syrian population. Herein, we report that high-risk HPVs type 16, 18, 33, 45, 51, 52 and 58 are frequently present in colorectal cancer in this population. Therefore and based on previous studies and present data, we conclude that the most frequent high-risk HPV types, in the Syrian population, are 16, 18, 33, 35, 45, 51, 52 and 58. Thus, our data suggest that it will be useful to use the new generation of HPV vaccine to protect the Syrian population from high-risk HPVs and their associated cancers.

Association of polymorphisms in one-carbon metabolizing genes with breast cancer risk in Syrian women.

Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.

P53 gene polymorphisms and breast cancer risk in Arab women.

The association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk has been studied in many human populations with conflicting conclusions. However, similar studies in Arab women are not available, and the status of these polymorphisms in this ethnic population is not known. We investigated the status of four known p53 gene polymorphisms and their possible role in breast cancer risk in Arab women. Genotyping was performed for 288 breast cancer women and 188 controls to determine Pro47Ser, Arg72Pro, Intron 3 Ins16 bp and intron 6 (G > C) polymorphisms. The p53 variant Pro47Ser was detected only in one Kuwaiti breast cancer patient and was not detected in any of the control subjects. Frequency of Arg/Arg at codon 72 was 26.6% in controls and 28.1% in patients, Arg/Pro frequency was 59.6% in controls and 69.4% in patients, the Pro/Pro genotype was 13.8% in controls and 2.4% in patients. We observed that women with Pro/Pro genotype have decreased risk for developing breast cancer (OR=0.166, 95% CI=0.067-0.411, p<0.001). The intron 3 genotypes were A1/A1 (48.9%), A1/A2 (40.6%) and A2/A2 (10.5%) in controls and A1/A1(42.4%), A1/A2 (52.8%) and A2/A2 (4.8%) in cases. The intron 6 genotypes were 92.4% (GG), 7.6% (GC) and 0% (CC) in controls and 96.5% (GG), 3.5% (GC) and 0% (CC) in cases. No statistically significant differences between patients and controls were observed for intron 3 and intron 6 polymorphisms. Our data show that proline homozygosity at p53 codon 72 is associated with decreased breast cancer risk in Arab women.