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.

Kidney stone composition in the Kingdom of Saudi Arabia
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INTRODUCTION: Urolithiasis is a globally-distributed disease; however, its prevalence varies across countries and regions. Countries in the Middle East have been reported to have particularly high nephrolithiasis prevalence rates. To date, however, we have an incomplete understanding of the composition of stones seen in this region. Therefore, we performed a study to characterize stone composition over a 14-year period in the Eastern Province of the Kingdom of Saudi Arabia (KSA). MATERIALS AND METHODS: A retrospective review of all adult patients who had the composition of their upper urinary tract calculi analyzed at Johns Hopkins Aramco Healthcare (JHAH) between 1999 and 2013 was performed. Patient demographics and pathology results were obtained from the electronic medical record. RESULTS: A total of 1,747 stones were analyzed in the study period. The results are presented in the Table. Male patients predominated (79%). For both men and women, the majority of stones were calcium oxalate: 85.2% male, 85.9% female. Uric acid stones were the next most common: 10.1% male; 9.0% female. Overall, there were no significant differences between gender with regards to the distribution of stone types. CONCLUSION: This study represents one of the largest characterizations of stone composition in the Middle East. There remains a significant gender disparity in stone prevalence in the Eastern Province of KSA, with males affected to a significantly greater extent. Calcium oxalate is the most common type of stone, and this is true for both men and women. Future investigations of dietary and environmental factors can build on these initial epidemiologic findings.
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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.

Primary ocular adnexal mantle cell lymphoma with distant spread and involvement of the contralateral eye one year later; a case report and literature review.

We herein report a middle-aged gentleman who initially presented with ocular adnexal mantle cell lymphoma (MCL) on the right eyelid. The lesion was excised and the patient was treated with radiation therapy. During the initial presentation, a PET CT was performed and did not reveal disease involvement beyond the eyelid. The patient presented 3 months later with ocular adnexal MCL of the contralateral eye. Re-evaluation using PET CT revealed a slight increase in the uptake in several lymph nodes and the spleen, which, after biopsy, confirmed systemic MCL. The patient was started on six cycles of chemotherapy. The patient also underwent autologous hematopoietic stem cell transplant. Approximately 80% of primary ocular adnexal lymphomas are B-cell in origin, with MCL being the rarest subtype constituting only 5% of B-cell ocular adnexal lymphomas. Despite its rarity, it is crucial for clinicians to detect the entity early and ensure rapid initiation of appropriate therapy.

A rare case of facial cutaneous Rosai-Dorfman disease clinically mimicking basal cell carcinoma followed by multiple myeloma after 2 years.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis disorder characterized by the proliferation of histiocytes within the lymph nodes. Extranodal involvement can occur; however, only 10% of extranodal RDD involve the skin. We present a unique case of a 66-year-old woman with cutaneous RDD followed by the development of multiple myeloma (MM). To our knowledge, this is only the second reported case where RDD preceded a diagnosis of MM, with the first documented instance occurring in 2018. The patient presented to the dermatology clinic with a 5-year history of painless, solitary lesion over the right cheek. Local examination revealed a single 6 mm x 7 mm well-circumscribed pearly telangiectatic lesion resembling basal cell carcinoma over the right nasolabial fold and cheek. The lesion was excised with a 3 mm circumferential margin. Histopathology showed a mixed lymphohistiocytic cell infiltrate with emperipolesis and immunohistochemical staining patterns consistent with RDD. Two years later, the patient presented with hip pain and was diagnosed with MM. She was treated with lenalidomide, bortezomib, and dexamethasone, and was later maintained on lenalidomide. Our case adds to the limited evidence suggesting a potential association between RDD and MM. Further research in this field is required to promptly identify and manage patients with such a presentation in the future.

Multiple cutaneous granular cell tumors involving the shoulder and foot in a child; a rare case report.

Granular cell tumors are rare soft tissue neoplasms derived from Schwann cells and are characterized by their infiltrative, non-encapsulated nests and sheets of polygonal cells with fine eosinophilic cytoplasmic granules on histology. Herin, we report a case of a 10-year-old Saudi female who presented to the hospital with multiple asymptomatic skin lesions, the largest located on the right shoulder and left foot. Preoperative workup revealed the absence of liver metastasis, and the patient underwent complete surgical excision successfully. Histopathology revealed ill-defined proliferation of large bland cells with prominent eosinophilic granular cytoplasm and mild epithelial hyperplasia consistent with granular cell tumors. Granular cell tumors are a rare entity that represent only 0.5% of all soft tissue tumors. They have characteristic histological features and can present with both malignant and being features. Due to the rarity of this disease, further research is needed to enhance our understanding and improve recognition in future practice.

Localized conjunctival amyloidosis clinically presenting as pyogenic granuloma.

Primary amyloidosis of the conjunctiva and eyelid is a rare and often misdiagnosed condition. It is characterized by the deposition of insoluble amyloid fibrils, which are misfolded proteins, in the body. Amyloidosis can be systemic or localized with different types of amyloid fibril proteins identified using mass spectrometry. Ocular involvement in amyloidosis can lead to corneal dystrophies, glaucoma, vitreous opacities, and other symptoms. Diagnosis involves clinical examination and histopathological assessment. Treatment options depend on the extent of involvement and may include surgical excision, glaucoma management, vitrectomy, or liver transplantation in rare cases. We present a rare case of localized conjunctival amyloidosis initially misdiagnosed as pyogenic granuloma, with clinical symptoms of ptosis, periorbital swelling, and conjunctival lesions. The patient underwent excision of the lesions, and subsequent evaluation did not reveal systemic amyloidosis. Ocular amyloidosis requires careful diagnosis and consideration of systemic involvement for appropriate management.

A case of primary conjunctival follicular lymphoma presenting as nasolacrimal obstruction.

We herein report a 76-year-old male who presented to the ophthalmology clinic after complaining from excessive lacrimation for ~6 months prior to presentation. He reports previously undergoing a nasolacrimal recanalization procedure in attempts to resolve his symptoms, but reported no improvement. On examination, a mass on the nasal conjunctiva around the medial canthus of the right eye was noted and subsequently excised. The findings support the diagnosis of low-grade follicular lymphoma. The patient was referred to radiation oncology for radiation therapy and received a total dose of 2400 cGy. Most ocular adnexal lymphomas are B-cell in origin, with follicular lymphomas being one of the rarest forms of such lymphomas. The most common translocation reported in over 85% of follicular lymphomas of the ocular adnexa is t(14; 18) (q32; q21). Traditional treatment options typically include a mix of chemical, surgical, and radio-oncological interventions.

High-grade appendiceal mucinous neoplasm presenting as renal colic; a case report and review of literature.

High-grade appendiceal mucinous neoplasms (HAMN) are rare mucinous appendiceal tumors that are mostly incidentally discovered and histologically show marked cytoplasmic atypia. We report a 62-year-old female patient who was diagnosed with acute right flank pain mimicking renal colic. Abdominal and pelvis CT scans showed no calculi or hydronephrosis. Incidentally, a markedly distended retrocecal appendix was identified and an appendectomy was performed. Histopathology revealed an HAMN of size 5.8 cm. HAMN are one of the rare and somewhat recently described epithelial appendiceal tumors. The latest 2019 classification is based on histologic appearance and on the consensus for classification and pathologic reporting of Pseudomyxoma peritonei and associated appendiceal neoplasia (Peritoneal Surface Pathology Group International, modified Delphi process). Histologically, appendiceal mucinous lesions are classified as nonneoplastic/mucocele and neoplastic lesions with separate subcategorization. Despite its rarity, it is crucial for clinicians to be aware of HAMN to distinguish it from other clinical differentials.

Longevity of Immunoglobulin-G Antibody Response Against Nucleocapsid Protein Against SARS-CoV-2 Among Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the latest pandemic and the most significant challenge in public health worldwide. Studying the longevity of naturally developed antibodies is highly important clinically and epidemiologically. This paper assesses the longevity of antibodies developed against nucleocapsid protein amongst our health-care workers. Methods: This longitudinal cohort study was conducted at a tertiary hospital, Saudi Arabia. Anti-SARSsCoV-2 antibodies were tested among health-care workers at three-point intervals (baseline, eight weeks, and 16 weeks). Results: Of the 648 participants, 112 (17.2%) tested positive for Coronavirus (COVID-19) by PCR before the study. Of all participants, 87 (13.4%) tested positive for anti-SARS-CoV-2 antibodies, including 17 (2.6%) participants who never tested positive for COVID-19 using rt-PCR. Out of the 87 positive IgG participants at baseline, only 12 (13.7%) had remained positive for anti-SARS-CoV-2 antibodies by the end of the study. The IgG titer showed a significant reduction in values over time, where the median time for the confirmed positive rt-PCR subgroup from infection to the last positive antibody test was 70 (95% CI: 33.4-106.5) days. Conclusion: Health-care workers are at high risk of exposure to the SARS-CoV-2 virus, and contracting an asymptomatic infection is not unlikely. Developing and sustaining natural immunity differs from one person to another, while the rate of positive IgG anti-SARS-CoV-2 wanes over time. Clinicaltrialsgov Identifier: NCT04469647, July 14, 2020.

Immunotactoid glomerulopathy: clinicopathologic and proteomic study.

BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile. METHODS: The characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases. RESULTS: Presentation included proteinuria (100%), nephrotic syndrome (69%), renal insufficiency (50%) and microhematuria (80%). Hypocomplementemia was present in 46% and a serum M-spike in 63%. Hematologic malignancy was present in 38%, including chronic lymphocytic leukemia in 19%, lymphoplasmacytic lymphoma in 13% and myeloma in 13%. The pattern of glomerular injury was membranoproliferative (56%), membranous (31%) or proliferative (13%) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69% and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50% had remission, 33% had persistent renal dysfunction and 17% progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component. CONCLUSIONS: Hematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.

A Cohort Study of Seroprevalence of Antibodies Against SARS-CoV-2 Infection Among Healthcare Workers at a Tertiary Hospital in Saudi Arabia.

Background: The nature of the healthcare workers' jobs standing at the frontline against the coronavirus disease 2019 (COVID-19) puts them at a higher risk of unknowingly contracting the disease and potentially contributing to the spread. This study aims to assess the overall positive seroconversion prevalence of SARS-CoV-2. Methods: This is a longitudinal cohort study of healthcare workers at Johns Hopkins Aramco Healthcare (JHAH). JHAH is a tertiary hospital located in Dhahran serving patients in several districts in the Eastern Province of Saudi Arabia. Participants were recruited between June and December 2020. Each participant had a serology blood test and completed the World Health Organization's risk factor assessment questionnaire. Results: This study included 682 participants working in JHAH, representing 15.7% of our population. Out of the 682 participants, 15.2% had a positive SARS-CoV-2 rt-PCR before taking part in the study. However, only 87 tested positive for SARS-CoV-2 antibodies, a prevalence of 12.7% of all participants. Out of the 87 positives for SARS-CoV-2 antibodies, 17 participants never tested positive for COVID-19 rt-PCR, a prevalence of 2.9%. Moreover, not properly using alcohol-based hand rub or soap and water after the risk of body fluid exposure and wearing personal protective equipment when indicated were found to be statistically significant to having a positive SARS-CoV-2 IgG assay. Conclusion: Positive seroconversion rate was considerably low during the first wave of COVID-19 amongst JHAH's healthcare workers and similar to other healthcare organizations in Saudi Arabia. Seropositivity correlated significantly with following infection prevention and control recommendations. Clinicaltrialsgov Identifier: NCT04469647.

Prevalence of dermatofibrosarcoma protuberans in Saudi Arabia over 24 years.: A retrospective single-institution study.

OBJECTIVES: To conduct a descriptive clinicopathological and demographic analysis of dermatofibrosarcoma protuberans among Saudi patients attending a tertiary care center in the eastern province of Saudi Arabia. METHODS: This retrospective, single-center study reviewed the medical records and pathology reports of Saudi patients attending a tertiary center (Johns Hopkins Aramco Health Care) in Dhahran, Saudi Arabia from 1995 to 2019 to identify all cases of dermatofibrosarcoma protuberans. Demographic and phenotypic data were also analyzed. RESULTS: Thirty-five Saudi patients were identified as having dermatofibrosarcoma protuberans. Females constituted 68.6% of patients. The trunk was the most common site of involvement (54.3%), followed by the lower extremities (34.3%), upper extremities (8.6%), and head and neck (2.9%). The mean tumor size was 2.9 cm (standard deviation: ±2.0). There was only one case of distant metastasis of fibrosarcomatous dermatofibrosarcoma protuberans. CONCLUSIONS: Dermatofibrosarcoma protuberans was not frequently encountered in Saudi patients in a tertiary center that treats approximately 187,668 patients. Dermatofibrosarcoma protuberans disease patterns and demographic data were similar to those reported worldwide. Further studies are required to characterize dermatofibrosarcoma protuberans in the Saudi population.

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.

Adenolipoma of the Skin: A Report of 11 Cases.

INTRODUCTION: Adenolipoma is a relatively recently described lesion representing a rare variant of lipoma in which eccrine glands and ducts are found interspersed amongst mature adipose tissue. This benign lesion was first described by Hitchcock et al. in 1993 [J Am Acad Dermatol 1993; 29: 82-85]. The next case series was written by Ait-Ourhrouil and Grosshans [Ann Dermatol Venerol 1997; 124: 845-848] in which they deemed adenolipoma a misnomer based on the pathophysiology of the lesion and suggested the name peri-sudoral lipoma instead. According to our knowledge, this case series would be the third in the literature to report cases of adenolipoma in an attempt to increase awareness of this entity. METHODS: We performed a retrospective review of adenolipoma cases from 2004 to 2014 at our institute. RESULTS AND CONCLUSIONS: Upon review of all adenolipomas diagnosed at our institute between 2004 and 2014, 11 cases in total were identified. Histologically, these lesions consisted of an admixture of adult-like adipose tissue and scattered eccrine glands and ducts. 4 cases also showed areas of myxoid changes; 2 showed scattered mast cells amongst the adipose tissue, and only 1 showed the presence of apocrine glands in addition to the eccrine glands and ducts. The female to male ratio was 6: 5. The typical age ranged from 41 to 53 years. Adenolipomas were seen arising from various locations including the thighs, gluteal region, lower leg, shoulder, chest, and trunk. The majority of cases were not fully encapsulated and the size varied from 0.7 to 5.8 cm.

Mullerianosis of the Urinary Bladder: A Case Report.

Mullerianosis is a rare entity consisting of an admixture of 2 or more of the following tissues: endometriosis, endocervicosis, and endosalpingiosis. It most commonly affects the urinary bladder and affects females of fertile age. It presents clinically as hematuria, dysuria, and pelvic pain which may be associated with menstruation. Radiologically and macroscopically, it typically presents as a polypoid mass in the dome or posterior wall of the bladder. Histologically, it consists of glands of varying size lined by endometrial, endocervical, or tubal epithelium. Mullerianosis clinically and histologically mimics other benign and malignant lesions. Herein we report a case of mullerianosis of the urinary bladder. This is a rare lesion with less than 20 cases reported in the literature thus far. We believe raising awareness of this poorly recognized entity is of utmost significance in order to avoid misdiagnosis and the following unnecessary radical procedures.

HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.

AIM: Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated. METHOD: 518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC. RESULTS: Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%). CONCLUSIONS: Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.

Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis.

AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a tumor suppressor gene for most human cancers. It encodes the most active common human chromosomal fragile region, FRA3B. We studied the prevalence of loss of FHIT expression in various tumors and correlated its loss with various clinicopathologic features. METHODS: To determine whether the absence of FHIT expression correlates with clinical variables such as grade, stage, and survival time, we assessed FHIT expression using immunohistochemistry. More than 1,800 tumors from more than 75 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19% in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like grade, stage, tumor size, and lymph node metastasis showed correlation with loss of FHIT expression in some tumors. No difference was seen in the survival patterns and loss of FHIT expression in any of the tumor groups studied. CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep, multifactorial carcinogenesis process. FHIT may be altered at different stages in different types of cancers. Most of the tumors with a wider prevalence of loss of FHIT expression as an early event show a correlation with clinicopathologic features. However, in some of the tumors, FHIT expression is lost as a late event and is only seen in a fraction of the tumors.

High epidermal growth factor receptor amplification rate but low mutation frequency in Middle East lung cancer population.

Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be highly predictive of response to gefitinib (Iressa) therapy in lung cancer. Studies on Western and Japanese lung cancers have indicated substantial differences in the EGFR mutation frequency between these populations. To investigate the prevalence of EGFR in another distinct ethnic group, EGFR alterations were studied in 47 consecutive non small cell lung cancers from Saudi Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA sequencing. Detectable EGFR expression was seen in 69.8% of 43 interpretable cancers. Epidermal growth factor receptor amplification, present in 15.3% of 39 analyzable cancers, was strongly associated with high levels of EGFR expression (P = .0047). Only 1 exon 18-21 mutation was seen among 34 lung cancers that could be successfully sequenced. It is concluded that EGFR exon 18-21 mutations are rare in Middle East patients with lung cancer and occur in a similar range as in Western patients. The remarkable high rate of EGFR gene amplifications could potentially facilitate studies on the predictive role of gene copy number changes for response to anti-EGFR therapies in Middle East patient sets.