Soft Tissue Sarcomas: A 16-Year Experience of a Tertiary Referral Hospital in North Jordan.

Background and Objectives: Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods: All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results: In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR)(World WHO 2000-2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion: STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.

Immunopathology of Kikuchi-Fujimoto disease: A reappraisal using novel immunohistochemistry markers.

AIMS: Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. METHODS AND RESULTS: We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3-50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8-positive cells with predominant expression of T-cell receptor-ß. There were notable increases in the numbers of CD8-positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). CONCLUSIONS: The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.

Comparing BRAF mutation status in matched primary and metastatic cutaneous melanomas: implications on optimized targeted therapy.

BACKGROUND: Selective BRAF inhibitors have shown dramatic results with regard to improving outcome in patients with melanoma. Testing the BRAF status in matched primary and metastatic melanomas to optimize individual targeted therapy is not well investigated. METHODS: Extended BRAF testing using PCR for 9 mutations and VE1 immunohistochemistry for BRAF V600E detection on 95 lesions including 40 primary melanomas with their matched metastases (n = 42), recurrences (n = 9) and second primaries (n = 4) was performed. Nine patients had multiple metastases. RESULTS: V600E was the only identified mutation type; 35.4% of primary vs. 18.9% of metastatic melanomas. The overall primary-metastatic BRAF status discordance rate was 32.3% using PCR and 27.5% with immunohistochemistry, and was significantly more frequent in primary lesions with mutant BRAF (67%). Males and patients with metastasis to lymph nodes were less likely to be discordant compared to females and those with metastasis to other sites (p = 0.023). Discordant BRAF mutation status was predicted by multivariate binary logistic regression: the presence of a mutant BRAF in the primary melanoma [OR (95% C.I.) = 23.4 (2.4-229.7)] and female gender [OR = 10.6 (1.08-95)]. Inter-metastases BRAF concordance was 100% (6 comparisons). CONCLUSION: A high discordant rate implies the need for clinical trials addressing the response to targeted therapy in patients with discordant BRAF statuses between their primary and metastatic lesions.

BRAF analysis on a spectrum of melanocytic neoplasms: an epidemiological study across differing UV regions.

BRAF mutation has been linked to the development of melanocytic tumors in homogeneous Caucasian cohorts. The role of solar UV radiation (UVR) in BRAF mutation status is poorly understood. We studied the epidemiology of BRAF mutation across a spectrum of melanocytic neoplasms in populations with differing UVR rates. Extended testing for 9 mutation types was attempted on 600 melanocytic neoplasms including banal nevi (n = 225), dysplastic nevi (n = 113), primary (n = 172), and metastatic melanomas (n = 90). Specimens were collected from 4 countries with increasing UVR rates (in kJ/m/yr): Syria (n = 45; UVR = 93.5), Lebanon (n = 225; UVR = 110), Pakistan (n = 122; UVR = 128), and Saudi Arabia (n = 208; UVR = 139). UVR was estimated from 21-year averages from The National Center for Atmospheric Research database. The overall BRAF mutation rate was 49% (268 of 545) and differed significantly by the geographic location [34% Pakistan, 49% Lebanon, 67% Syria, and 54% Saudi Arabia; P = 0.001], neoplasm type (P < 0.001), and anatomical location (P < 0.001) but not with age (P = 0.07) and gender (P = 1.0). V600E was the predominant mutation type, found in 96.3% of the cases. Incidence of melanoma was significantly greater in BRAF-negative (39%) versus BRAF-positive (17%) groups. For BRAF-positive cases, less severe lesions were systematically more frequent (P < 0.001). Multivariate analysis indicated that BRAF mutation is predicted by neoplasm type, anatomical site, and geographic location. In our Near East cohort, BRAF mutation rates varied by geographic location but not based on UVR. BRAF-positive status was associated with less severe lesions.

Microscopic dysgerminoma associated with anti-Ma2 paraneoplastic encephalitis in a patient with gonadal dysgenesis.

We present a 27-yr-old female with gonadal dysgenesis (46, XY), who presented to our hospital with poor consciousness, aphasia, restlessness, and visual hallucination. Physical examination revealed normal breast development and normal external female genetalia. Computed tomography scan of the head and neck revealed the presence of brain edema, hydrocephalous, and a localized hypodense lesion in the hypothalamus. Her serum was positive for the anti-Ma2, which is associated with paraneoplastic encephalitis syndrome. Computed tomography of the abdomen revealed the presence of a 7.5×5.3×3.0 cm solid pelvic mass. Interestingly, a single microscopic focus of dysgerminoma was identified in a background of stromal fibrosis and focal dystrophic calcifications. No ovarian stroma or testicular tissue was identified. To our knowledge, this is the first case of gonadal dysgenesis presenting with anti-Ma2 paraneoplastic encephalitis with dysgerminoma. A discussion about paraneoplastic encephalitis with a microscopic dysgerminoma associated with anti-Ma2 antibody is presented.

Perivascular Epithelioid Cell Tumor (PEComa) of the Pancreas in a Patient with Ulcerative Colitis: A Case Report and Review of the Literature.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors of peculiar cells that are focally associated with blood vessels, and generally have a distinctive bi-phenotypic expression of both smooth muscle and melanocytic markers. There are several entities in the PEComa family, including tumors that arise in the soft tissues and viscera. Frequently affected organs include the lungs (sugar tumors), uterus, broad ligament, colon, small bowel, liver, and pancreas. Ulcerative colitis (UC) has been associated with the development of tumors, especially colorectal and hepatobiliary carcinomas. Rare cases of UC have been reported in the PEComa family of tumors, but none in the pancreas. Here, we present a case study of a 27-year-old female patient with a history of UC who developed PEComa of the pancreas, a unique association that has not been previously reported. We also review reported cases of PEComas in the pancreas, as well as PEComas at all anatomic sites associated with UC.

Massive Localized Lymphedema: Two Case Studies and Diagnostic Challenges.

Massive localized lymphedema (MLL) is an emerging clinical phenomenon predominantly observed in morbidly obese individuals. It presents both diagnostic and therapeutic challenges to clinicians due to its characterization by large, pendulous masses in the abdomen or thigh. MLL may resemble malignant conditions, such as liposarcoma, leading to unnecessary invasive interventions. This study presents two case studies: a 74-year-old male who succumbed to postoperative complications and a 56-year-old female who experienced successful recovery. These cases highlight the urgent need for robust diagnostic criteria and evidence-based management approaches for MLL. In addition, further research exploring the pathogenesis, risk factors, and potential connections among MLL, hypothyroidism, and angiosarcoma is essential.

Giant Ectopic Parathyroid Adenoma Arising in the Posterior Mediastinum. Report of Case and a Review.

We present a case of a greatly enlarged giant ectopic parathyroid adenoma that weighed 43 grams, which was located in the posterior mediastinum of a 74-year-old man. The patient presented with generalized weakness and decreased level of consciousness. He was found to have elevated level of serum calcium (19.9 mg/dl), and a subsequent assay of parathyroid hormone (PTH) was greatly elevated (2234 pg/ml). We report the course of management and outcome of the patient and present a review of the literature on giant ectopic parathyroid adenomas in the posterior mediastinum.

Snakebites in Jordan: A clinical and epidemiological study.

The epidemiology features and clinical symptoms associated with 121 cases of snakebite requiring admission to 24 hospitals in Jordan, during 2018-2020, are discussed. Ninety-six of them (79%) brought with them to the hospital the snake that bit them or a photograph of it. Echis coloratus was responsible for 68 of the bites and 6 fatalities. Sex ratio was 3.2 males: 1 female, with an overall average age of 27 ± 14.36 years. The highest incidence of bites was reported in September. Bites were most common on hands and legs. The period of hospitalization ranged from 1 to 36 days. Irbid and Karak governorates had the highest number of snakebites, most cases being reported from agricultural areas and among farmers. Clinical symptoms associated with five species of venomous snakes are described along with illustrative case histories. Symptoms associated with Echis coloratus bites included local swelling and necrosis, coagulopathy and bleeding, microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and chronic renal failure. Daboia palaestinae victims exhibited ecchymoses, local swelling and necrosis, with one case of angioedema. Other symptoms included thrombocytopenia, coagulopathy, microangiopathic hemolysis and local and systemic bleeding, as well as AKI. A single case of envenoming by Macrovipera lebetinus developed the following symptoms; swelling, severe pain, extensive ecchymoses, neutrophil leukocytosis, normochromic normocytic anemia and aggregated platelets with thrombocytopenia. Symptoms associated with two cases of Pseudocerastes fieldi included swelling that spread from bitten hands, and mild abnormalities of platelet count and bleeding time. Four cases of envenoming by Atractaspis engaddensis exhibited severe pain, local swelling, erythema, numbness and tissue necrosis. One of them developed acute systemic symptoms. The only antivenom currently available in Jordan, is VINS "Snake venom antitoxin (Biosnake)", manufactured in India using venoms of three African snakes that do not occur in Jordan. It proved clinically ineffective against envenoming by Jordanian Viperidae, failing to correct coagulopathy and life-threatening hemorrhage, and to prevent AKI.

Malignant Glandular Triton Tumor Arising in the Radial Nerve with Prolonged Survival: A Case Report and Review of the Literature.

Divergent differentiation is a well-known phenomenon in malignant peripheral nerve sheath tumors (MPNST) which occurs approximately in 15% of these tumors, usually towards mesenchymal elements. Differentiation towards epithelial components, however, is quite uncommon, and even exceptionally rare is concomitant mesenchymal and glandular differentiation. To our knowledge, only 14 cases of MPNST with both mesenchymal (rhabdomyoblastic) and glandular differentiation had been reported, and only two of these tumors had frankly malignant glandular components. Herein, we report the third such case. A 26-year-old male, without any of the stigmata of NF1, presented with a 2-year history of pain in his left shoulder and an elbow swelling of six-month duration. The tumor was initially diagnosed clinically as a neurofibroma at a local hospital. The patient underwent excision of the mass there, and pathological examination at that hospital showed the tumor to be MPNST. Six months later, the patient was referred to our hospital, a tertiary care medical center, with recurrent swelling at the same location. Histopathological material from the referral hospital was reviewed, and the tumor was diagnosed as MPNST with rhabdomyoblastic differentiation or malignant triton tumor (MTT) that contained in addition foci of malignant glandular epithelium. The patient refused any surgical intervention. He received three cycles of chemotherapy followed by radiotherapy with excellent response and marked reduction in the size of the tumor. The patient had prolonged survival for 10 years following the initial resection of the tumor.

Gastric Plexiform Fibromyxoma Arising in the Cardia in an Adolescent Male: A Rare Tumor with an Unusual Location.

Plexiform fibromyxoma of the stomach, also known as plexiform angiomyxoid myofibroblastic tumor, is a rare benign gastric mesenchymal tumor, first described in 2007, which usually arises in the gastric antrum and affects adults. Few cases have been reported in children and adolescents. It can present with different clinical manifestations including abdominal pain, dyspepsia, hematemesis, and vomiting. Preoperatively, this tumor is usually diagnosed as gastrointestinal stromal tumor (GIST), and the correct diagnosis is made only after histopathological examination following surgical resection. Most cases were reported from East Asia (China, Japan, and Korea), North America, and Europe. We report herein a unique case of plexiform fibromyxoma, the first to be reported from the Middle East, arising in the cardia of the stomach in a 16-year-old adolescent male, with a brief review of the literature.

Malignant teratoid tumor of the thyroid gland: an aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations-is the term "thyroblastoma" more appropriate?

Primary thyroid teratomas are exceedingly rare. Mature and immature variants recapitulate their gonadal counterparts (predilection for infants/children, triphasic germ layer differentiation, and favorable outcome). On the other hand, the so-called malignant teratomas affect predominantly adults and elderly, are highly aggressive, and, according to a few published cases, harbor DICER1 mutations. We describe three highly aggressive sporadic malignant teratoid thyroid tumors in 2 females (17 and 45 years) and one male (17 years). Histology showed triphasic neoplasms composed of solid nests of small primitive monomorphic cells embedded in a cellular stroma with primitive immature rhabdomyosarcoma-like (2) or pleomorphic sarcoma-like (1) phenotype. The third component was represented by TTF1+/PAX8+ primitive teratoid epithelial tubules reminiscent of primitive thyroid follicles and/or Wilms tumor, admixed with scattered respiratory- or enteric-type tubules, neuroepithelial rosettes, and fetal-type squamoid nests. Foci of cartilage were seen in two cases, but none contained mature organoid adult-type tissue or skin adnexa. SALL4 was expressed in the small cell (2) and stromal (1) component. Other germ cell markers were negative. Molecular testing revealed a known "hotspot" pathogenic DICER1 mutation in two cases. In addition, case 1 had a missense TP53 variant. This type of thyroid malignancy is distinct from genuine teratomas. The immunoprofile suggests primitive thyroid- or branchial cleft-like differentiation. Given that "blastoma" is a well-accepted terminology in the spectrum of DICER1-associated malignancies, the term "thyroblastoma" might be more convenient for these malignant teratoid tumors of the thyroid gland. Relationship of thyroblastoma to the DICER1 syndrome remains to be addressed.

Madura leg due to Exophiala jeanselmei successfully treated with surgery and itraconazole therapy.

Exophiala jeanselmei, also known as Phialophora jeanselmei, is a dematiaceous fungus widely distributed in nature. The organism can cause cutaneous, subcutaneous or systemic infections. An uncommon clinical presentation is eumycetoma, i.e., a subcutaneous infection associated with draining sinuses releasing clumps or granules of the fungus. We describe a case of a long standing mycetoma with several draining sinuses involving the left lower leg of a 47-year-old Saudi Arab male. The disease required extensive surgical excision coupled with intense antifungal chemotherapy to achieve cure.

Metastasizing Malignant Granular Cell Tumor (Abrikossoff Tumor) of the Anterior Abdominal Wall, with Prolonged Survival.

Malignant granular cell tumor (MGCT) is a rare high-grade mesenchymal tumor of Schwann cell origin. MGCTs commonly affect thigh, extremity, and trunk; however, involvement of the abdominal wall is quite rare. It has poor prognosis with 39% mortality rate in 3-year interval. We report a 50-year-old female who had MGCT arising in the anterior abdominal wall and developed massive metastatic deposits in both lungs and in the right inguinal lymph nodes, with prolonged survival for 11 years. A brief review of the literature is presented.

Carcinosarcoma of the Gallbladder with Chondrosarcomatous Differentiation and Intracytoplasmic Eosinophilic Hyaline Globules (Thanatosomes): A Report of a Case and Review of the Literature.

A 52-year-old woman presented with abdominal pain and vomiting. Computed tomography (CT) scan of the abdomen revealed a huge exophytic gallbladder mass displacing or invading the surrounding structures. The patient underwent radical cholecystectomy, transverse colectomy, distal gastrectomy, and liver bed resection. Histologically, the tumor showed both carcinomatous and sarcomatous components, with prominent chondrosarcomatous differentiation. In addition, several malignant cells showed intracytoplasmic eosinophilic hyaline globules (Thanatosomes). The tumor showed metastatic deposits to the omentum, the liver, and the peripancreatic lymph nodes. We report this unusual case and present a review of all cases of carcinosarcoma of the gallbladder with chondrosarcomatous differentiation.

Primary Chordoma of the Nasopharynx: A Rare Case Report and Review of the Literatures.

Primary chordoma of the nasopharynx is an extremely rare malignant tumor of notochordal origin in the extra-osseous axial skeleton. It presents as a soft tissue mass without involvement of the skull base bone (clivus) and may mimic other lesions of the nasopharynx. A 26-year-old male patient is presented with nasal obstruction and congestion for the last 3 years. Physical and radiological examination revealed a mass in the naso-oropharyngeal region. It was suspected to be a cystic mass or abscess on radiological imaging. However, histopathological examination revealed a chordoma. We review all 20 cases of primary nasopharyngeal chordoma reported previously in the literature. Nasopharyngeal chordoma should be considered in the differential diagnosis of nasopharyngeal mass due to its unspecific appearance on clinical and radiology examination.

Gastrointestinal stromal tumors. A clinicopathological study.

OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%). CONCLUSION: Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Mediastinal Ectopic Pancreas with Abundant Endocrine Cells Coexisting with Mediastinal Cyst and Thymic Hyperplasia.

Mediastinal ectopic pancreas is a rare condition with only 28 cases reported in the literature. Here we report a 21-year-old female patient who presented with dyspnea and intermittent severe chest pain of 7 years' duration. Computerized tomography scan (CT-scan) of the chest revealed a mediastinal cyst. The cyst was resected and it demonstrated on histopathological examination the presence of pancreatic tissue with increased number of islets of Langerhans, coexistent with mediastinal cyst and thymic hyperplasia. We made a review of all previously reported cases of this entity.

Gallbladder cancer in Eastern Province of Saudi Arabia: A retrospective cohort study.

BACKGROUND: There is paucity in the literature regarding gallbladder cancer in Saudi Arabia, possibly because it is not among the top 10 cancers diagnosed nationwide according to the Saudi Cancer Registry. Moreover, national or regional data on gallbladder cancer in Saudi Arabia have not been analyzed. The purpose of this study was to describe the presentation, disease stage, histology, and survival rates for gallbladder cancer in Saudi patients at a single institution between January 1, 2010 and December 31, 2017. MATERIALS AND METHODS: This was a retrospective study of 76 patients who presented to our hospital between January 1, 2010 and December 31, 2017, with established diagnosis of gallbladder carcinoma. The diagnosis was made either histopathologically following simple laparoscopic cholecystectomy or biopsy from metastatic liver lesion in patients with gallbladder mass, or the high suspicion of gallbladder carcinoma based on incidental radiological findings. Presentation, disease stage, histology, and treatment modalities were analyzed using descriptive statistics and frequency distributions. Survival rates were analyzed and presented using Kaplan-Meier curves. RESULTS: Based on initial analyses the disease was more frequent among women (62.0%) than men (39.0%). Surgical resection was attempted in 40.8% patients. The average age at presentation and diagnosis of gallbladder carcinoma was 62.4 years. The disease had two peaks, one at 51.0 years and the other between 66.0 and 70.0 years. The median survival time for the overall at-risk patients was only 1.0 year, while for stage IVB patients was 7.2 months. Adenocarcinoma not otherwise specified (NOS) was the most common histopathology type (75.0%), with most patients presenting with stage IVB disease (75.0%). Gallbladder carcinoma was incidentally detected in 42.1%, including three cases (3.9%) diagnosed at our hospital. CONCLUSIONS: Gallbladder cancer is a rare type of cancer in Saudi Arabia, and most patients are treated surgically, despite being mostly diagnosed at the advanced stage of the disease.

Aspiration cytology of brain abscess from a fatal case of cerebral phaeohyphomycosis due to Ramichloridium mackenziei.

Ramichloridium mackenziei is a dematiaceous fungus that usually causes cerebral phaeohyphomycosis. We describe the aspiration cytology findings of a case of cerebral abscess caused by R. mackenziei in a 66-yr-old Saudi woman who had a long standing history of diabetes mellitus and a recent diagnosis of systemic lupus erythematosus. She was on long-term corticosteroid therapy. The patient developed rapidly progressive multiple brain abscesses and died despite aspiration of the abscess and administration of intravenous amphotericin B lipid complex and voriconazole.