importance of second opinion in surgical pathology referral material of lymphoma

To evaluate the importance of inter-institutional second opinion surgical pathology review of lymphoma, and identify the lymphoma pathologic mimics. The surgical pathology material of patients referred to 2 tertiary care hospitals in the western region of Saudi Arabia [King Faisal Specialist Hospital and Research Centre and King Abdulaziz University Hospital, Jeddah, Saudi Arabia], for evaluation or therapy for lymphoma over a 10-year period [August 2001 to August 2011], were reviewed. This study included only cases in which the patient referred with a diagnosis previously made at the primary institution. Of 560 cases, the second opinion diagnosis differed significantly from the initial diagnosis in 39 cases [7%]. These include changing the diagnoses from lymphoma to non-lymphoma lesions, change the type of lymphoma with major clinical impact, and change from reactive/non-diagnostic to lymphoma. Second opinion surgical pathology for lymphomas can result in major therapeutic and prognostic modifications. Thus, review of the original histologic material is recommended prior to a major therapeutic decision, and to maximize the discovery of clinically relevant major disagreements. Stringent adherence to institution's second opinion policy is an important quality assurance measure in surgical pathology

Ewing's sarcoma family tumors in the western region of Saudi Arabia. A pathological experience from 2 tertiary medical centers

To review the pattern of Ewing's sarcoma/primitive neuroectodermal tumor [ES/PNET] in 2 medical centers in the western region of Saudi Arabia. We retrospectively analyzed the pathological data of patients diagnosed with ES/PNET in 2 tertiary medical centers in the western region of Saudi Arabia [King Abdulaziz University Hospital, [March 1995 to November 2011], and King Faisal Specialized Hospital [April 2003 to 12 December 2010]]. Age, gender, and site of tumors were analyzed. Sixty-nine cases were diagnosed as ES/PNET. The age range was 3-62 years [mean 22 years]. Male cases were more than the female. Approximately 28.9% of cases presented within the skeleton, and 71.1% cases were presented as a soft tissue disease. Bone affection was higher in the iliac bone. Long bones were affected at a lower frequency. Soft tissue affection showed a higher incidence in the head and neck region followed by the lower limb. The current study represents a review of a large number of Ewing's sarcoma family of tumors in western Saudi Arabia. Cases showed clinicopathological features comparable to those reported from other locations worldwide apart from relatively higher soft tissue affection than skeletal affection and a higher incidence of head and neck involvement by soft tissue ES/PNET. Further, multicenter studies [epidemiological and genetic] are recommended to obtain profiling of the disease and effect on outcome and therapy

Metastatic breast neuroendocrine tumor from the rectum

Metastatic breast neuroendocrine tumor is an exceedingly rare entity. They are commonly initially misdiagnosed as primary breast carcinoma. Correct diagnosis of this tumor is crucial owing to the different clinical management from primary breast tumor. We report an additional case of metastatic breast neuroendocrine tumor from the rectum that behaved in an aggressive fashion and failed to respond to chemotherapy treatment

Kikuchi-Fujimoto disease. Histiocytic necrotizing lymphadenitis

Kikuchi-Fujimoto disease [KFD], or histiocytic necrotizing lymphadenitis, is a self-limited disease of complex and unclear etiology. Clinically and microscopically, it may mimic malignant lymphoma and other non-malignant diseases. Recognition of this entity is crucial, as mistaking this disease as lymphoma has major clinical consequences. Although KFD is a well-recognized entity in the literature, many clinicians and pathologists are still unaware of its existence. In this article, a review of KFD is provided with special emphasis on the pathogenesis and pathological differential diagnosis of this disease

Castleman's disease. Update on pathogenesis

Castleman's disease [CD] is an unusual lymphoproliferative disorder that may mimic lymphoma clinically and pathologically. It is classified clinically as localized and multicentric types, and pathologically as hyaline vascular and plasma cell types. It is associated with increased risk of lymphoma and follicular dendritic cell tumors. The pathogenesis of CD is still controversial and complex. Active research is ongoing to highlight more on the etiopathogenesis of this entity. The aim of this article is to review the literature on pathogenesis of CD and to focus on the possible role of viruses in the development of this disease

Post transplant lymphoproliferative disorder after autologous hematopoietic cell transplantation for hodgkin's lymphoma

Post-transplant lymphoproliferative disorder [PTLD] is a very rare complication post autologous bone marrow transplant with few cases reported so far. We report a case of a child with history of classic Hodgkin's lymphoma, nodular sclerosis type, who was treated with autologous stem cell transplantation Three mounths after the transplant, he developed bilateral cervical lymphadenopathy splenomegaly, neutropenia and thrombocytopenia Excisional biopsy of a left cervical lymph node revealed PTLD. The morphological pattern of the PTLD was combined monomorphic and polymorphic with plasmacytoid/plasmablastic differentiation expressing CD20 and CD79a. Kappa and lambda light chain stains show clear evidence of lambda light chain restriction. Immunohistochemistry stain and in situ hybridization for EBV [LMP-1] were positive for EBV. PCR study reveals a monoclonal B-cell proliferation with immunoglobulin heavy chain gene rearrangement. The patient was treated with predinsolone as 2 mg/kg/day over 2 weeks with tapering over the following 3 months. The white cell count recovered with regression of splenomegaly and cervical lymphadenopathy on his last visit to outpatient clinic he was in good health with normal laboratory parameters 2 years after the diagnosis of PTLD

Primary pancreatic tuberculosis mimicking neoplasm

Tuberculosis of the pancreas is extremely rare. Diagnosis of primary tuberculosis of the pancreas is often missed, because of very low prevalence and as most of the time it mimics pancreatic tumors. We searched for the cases of tuberculous pancreatitis [TP] among all the patients who underwent exploratory laparotomy or Whipple procedure for a pancreatic mass at King Faisal Specialist Hospital, Jeddah. We review the clinical, radiological and pathological findings of those cases together with a literature review. Three cases of TP were identified; two males and one female. The age of the patients is 56, 63 and 69 years. All the patients presented with obstructive jaundice and had laparotomy for pancreatic mass. Frozen and permanent sections evaluation revealed necrotizing granulomatous inflammation that is consistent with TB that was confirmed by microbiology culture. All the patients received post operative antituberculous treatment and all are in a good condition after 1-2 years of follow-up. We conclude that although TP is very rare entity. it should be considered in the differential diagnosis in patients who present with a pancreatic mass. Frozen sections evaluation at laparotomy is usually helpful for confirmation of the diagnosis and providing material for mycobacterial culture

Gastrointestinal stromal tumors in western Saudi Arabia

To determine the pattern of gastrointestinal stromal tumors [GIST] in the population of 2 large tertiary centers in the western province of the Kingdom of Saudi Arabia [KSA]. This retrospective study used cases diagnosed as GIST at the histopathology laboratories of King Abdul-Aziz University Hospital between January 2000 and October 2009, and King Faisal Specialist Hospital and Research Center, Jeddah, KSA, between January 2002 and December 2008. Additionally, cases diagnosed as gastrointestinal spindle cell tumors, sarcomas, schwannomas, leiomyomas, and leiomyosarcomas at King Abdul-Aziz University Hospital between January 1995 and December 1999 prior to the introduction of CD117 immunostain testing in the lab were tested for it. Positive cases were included in the study. Age and gender of the patients, as well as tumor location, maximum diameter, and mitotic count were analyzed. Thirty-seven cases were found in which the mean age was 55.6 years. Nineteen tumors were located in the stomach [51.4%], 7 in the small bowel [18.9%], 2 in the colorectum [5.4%], 4 in the mesentery [10.8%], and 5 in the abdomen [13.5%]. Fifteen cases [40.5%] were high risk, 13[35.2%] were intermediate risk, 3 [8.1%] were low risk, and one case [2.7%] was very low risk for aggressive behavior. The GISTs are more prevalent in Saudi Arabia than is generally thought. Most cases occurred in male adults over 40 years of age. The stomach is the most frequent location of occurrence. Most tumors are the high-risk group

Histopathological pattern of thyroid lesions in western region of Saudi Arabia

Partial or complete thyroidectomies are frequently encountered by the practicing pathologist and the possibility of neoplastic disease is of major concern in patients with thyroid nodules. Pathological evaluation of those specimens ranged from non-neoplasticlesion to highly aggressive malignancy. This study aimed to document the frequency of different patterns of thyroid diseases as presented to pathology departments at King Abdul-Aziz University Hospital [KAUH] and King Faisal Specialty Hospital and Research centre [KFSHRC] within the last twelve years. All specimens presented to pathology departments at KAUH [1997-2008] and KFSHRC [2000-2008] as thyroidectomies [partial or complete] were retrospectively reviewed and categorized according to their histological appearance. The total number of the studied cases was 845 cases. The age of the patients ranged between 9 and 93 years. One hundred seventy eight were males and 667 were female [male to female ratio; 1:3.7]. The reviewed cases were classically categorized into two main groups; Non-neoplastic [494; 58.5%] and Neoplastic [351; 41.5%]. The non-neoplastic group includes: Multinodular Goiter [311 cases; 36.8%], hashimoto/chronic lymphocytic thyroiditis [64 cases; 7.6%], single hyperplastic nodule [51 cases; 6%], Grave's disease [8 cases; 0.9%], miscellaneous [58 cases; 6.9%]. The neoplastic group includes benign category represented by "Adenomas" and includes 94 cases [11% of all cases, and 26.8% of neoplastic cases] and the malignant category includes 256 cases, representing 30.3% of all studied cases and 73% of the neoplastic category. Two hundred and nine cases [81.6% of malignant] were papillary carcinoma. Thyroid lesions are more common in Saudi female. The majority of the thyroid nodules in Saudi are non-neoplastic. Papillary carcinoma is the commonest type of thyroid cancer in Saudi society. Thyroid neoplasm is rare in Saudi children

Prostate inflammation. Association with benign prostatic hyperplasia and prostate cancer

To study the association and possible relationship of prostate inflammation with benign prostatic hyperplasia [BPH], and prostate cancer. The medical records and pathological findings of all Saudi patients who underwent transrectal ultrasound guided prostatic needle biopsies in King Abdulaziz University Medical City, Jeddah,Kingdom of Saudi Arabia from June 2003 to June 2008 were reviewed retrospectively. The indications for biopsy were elevated levels of serum prostate specific antigen, abnormal findings on digital rectal examination, or both. The specimens harboring inflammation, adenocarcinoma, BPH, or their combinations, were selected and included in the study. A total of 214 patients were selected with an age ranging from 37-100 years [median=68]. Inflammation was histologically evident in 88 patients. Of them, only one demonstrated acute inflammation, while 87/88 demonstrated chronic inflammation with, or without acute inflammation. Histopathologic features were categorized into 3 main categories: inflammation alone [12/214, 5.6%], BPH category [126/214, 58.9%], and cancer category [76/214, 35.5%] patients. The last 2 categories also included cases associated with inflammation. In the overall analysis of 214 specimens, BPH with inflammation was more prevalent than cancer with inflammation [43/214 [20.1%] versus 33/214 [15.4%]]. In a subgroup analysis within each category, inflammation was less prevalent in the BPH category compared to the cancer category [43/126 [34.1%] versus 33/76 [43.4%]]. The association between chronic inflammation and both BPH and cancer is obvious in our study. Further studies are needed to substantiate this observation, and to clarify the magnitude of association of inflammation with BPH compared to cancer

clinicopathologic patterns of prostatic diseases and prostate cancer in Saudi patients

To determine the clinicopathologic patterns of prostatic diseases in Saudi patients, with special emphasis on prostate cancer [PCa]. The records of patients who underwent histopathological examinations of their prostatic specimens in King Abdulaziz University Medical City and King Faisal Specialist Hospital, Jeddah, Kingdom of Saudi Arabia, between June 2003 and June 2008 were reviewed retrospectively. The age, indications for biopsy, histological diagnosis, and Gleason grading of cancer patients, were studied. The study included 330 patients aged 37-100 years [median=68]. Specimens included 233 transrectal ultrasound [TRUS] biopsies, 85 transurethral resection of the prostate [TURP], 8 simple prostatectomies, 3 radical prostatectomies, and one radical cystoprostatectomy. Indications for TRUS guided biopsy in PCa patients were elevated prostate specific antigen [PSA] [85.2%], abnormal digital rectal examination [5.5%] or both [9.3%]. Prostate specific antigen values <4 ng/ml were found in 13.6% of PCa patients. Among others, adenocarcinoma was found in 28.5%, benign prostatic hyperplasia [BPH] alone in 43.3%, BPH with inflammation in 20.3% and inflammation alone in 4.2%. In specimens of TURP or simple prostatectomy for apparently benign disease, incidental PCa was detected in 14/93 [15%]. The Gleason sum of >/= 6 was found in 92.8% of patients. The incidence of prostate cancer in Saudi Arabia is low compared to the western countries. However, incidental PCa detected in presumed benign disease appears to be rising. Further future studies addressing this issue are needed to confirm the potential rising trend, and its possible etiology. Our findings support the recommendations to lower the PSA cutoff value for prostatic biopsy to 2.5 rather than 4ng/ml

Multiple primary malignancies of thyroid, kidneys and prostate: synchronous and metachronous presentation in one patient

Synchronous appearance of 2 different primary malignant neoplasms is a rare phenomenon. We describe a patient with Synchronous presentation of 3 primary carcinomas included prostate carcinoma [PCA] and bilateral renal cell carcinoma [RCC]. papillary and classic clear cell types. Furthermore previous history indicated the presence of thyroid papillary carcinoma [TPCA] that was resected 10 years ago. Immunohistochemistry was applied to confirm the primary nature of these neoplasms. The patient is in a good health 1 year following total prostatectomy and bilateral partial nephrectomies. We report this very rare case, which up to our knowledge is the first case that represents the combination of carcinomas of thyroid, prostate and both kidneys in one patient and we emphasize the importance of immunohistochemistry to document the primary nature of such neoplasms

Lack of detection of human papillomavirus 18 in prostate carcinoma: immunohistochemistry analysis

Human papillomavirus [HPV] is the cause of the most common sexually transmitted diseases [STDs] of viral etiology worldwide. The association between HPV infection and prostatic carcinoma [Pca] is controversial issue. In this study the presence of HPV 6, 11 [low risk] and HPV 18 [high risk] was tested in prostate cancer of Saudi patients. A monoclonal antibody [NCL-HPV-4C4] specific for HPV types 6, 11, 18 [novocastra, United Kingdom] was used in formalin-fixed, paraffin-embedded tissue specimens obtained from patients with Pca [n: 32] at King Abdulaziz Hospital [Jeddah, Saudi Arabia]. Standard immunohistochemistry avidin-biotin peroxidase complex technique was used. The study was done in 2007. The age of patients ranged between 55 and 90 years. Gleason grade for the cases was as follows; score 6 [6 cases], score 7 [12 cases], score 8 [10 cases] and 9 [4 case]. None of the cases of Pca stained positively for HPV types 6, 11, 18. Normal, atrophic and hyperplastic epithelium showed also negative immunoreactivity. The results of the current study indicated that HPVs type 6, 11, 18 are not detected by immunohistochemistry in Pca and is less likely to play an important role in the pathogenesis of Pca. It lends support to the evidences against the association between Pca and HPV 18 infection. More evaluation of the different HPV types should be performed in prostate cancer specimens

Investigation of the biological significance of p53 tumor suppressor gene and Ki-67 in colorectal carcinoma resected from Saudi patients: An immunohistochemical analysis

p53 protein accumulation has been shown to be an unfavorable prognostic parameter in many human cancers, but findings in colorectal carcinoma [CRC] are equivocal. The objective of this study is to evaluate the value of p53 and Ki-67 as prognostic markers in patients with colorectal carcinoma. We conducted a retrospective analysis on 56 colorectal cancer specimens resected at King Abdulaziz university hospital, Jeddah, Saudi Arabia [40 cases of left colon and 16 from right colon]. Immunohistochemistry [IHC] was performed on formalin fixed paraffin embedded tissue using the avidin-biotin peroxidase complex method. Antibodies to p53 [DO7] and Ki-67 were used. This was correlated with the following clinicopathologic parameters: patient sex, age and survival; pathological stage, and grade of the tumors. Among the 56 cases of colorectal cancer [male/female=1.3; mean age 54.9 years, range 30-80 years], 85.7% [n=48] of tumors were positive for p13 IHC. Ki-67 was positive in 94% [n=53]. The p53 positivity in different stages was as follows [2/2 stage A, 23/28 stage B, 15/18 stage C and 8/8 stage D]. The positivity of p53 according to tumor differentiation was as follows: [well differentiated 6/6, moderately differentiated 38/45, poorly differentiated 4/5]. P53 was positive in 34/40 of left colon [including rectosigmoid] and in 14/16 of right colon carcinoma. Imunoreactivity for p53 was seen in adenomatous epithelium only in 8/22 cases. Although p53 and Ki-67 expression expresse4 strongly in cancer compared to normal tissue [p<0.05], there was no relation with survival, grade or Dukes' stage of the tumor. P53 cannot be considered as independent prognostic marker in colorectal carcinoma

Detection of human herpes virus-8 in kaposi sarcoma and other vascular tumors; immunohistochemical analysis

The diagnostic distinction of some vascular tumors and Kaposi's sarcoma [KS] can be sometime difficult. Recently, a monoclonal antibody to human herpes virus- 8 latent nuclear antigen-1 has been demonstrated in Kaposi's sarcoma. In this study the usefulness of this antibody is evaluated to differentiate Kaposi's sarcoma from the other vascular lesions. Formalin-fixed, paraffin-embedded tissue sections [4 micro m] from 20 cases of Kaposi sarcoma, ten cases of capillary hemangioma [pyogenic granuloma], five cases of angiosarcoma, three cases of hemangioendothelioma, three cases of vascular transformation of lymph nodes were examined immunohistochemically for HHV-8 using mouse monoclonal antibody [NCL-HHV8-LNA], Novocastra, United Kingdom. It is specific for human herpesvirus type 8 latent nuclear antigen-1 [LNA-1]. Nuclear staining in tumor cells was considered a positive result. HHV-8 stain showed strong, diffuse, nuclear staining for human herpes virus 8 latent nuclear antigen-1 in all, 20/20 cases of Kaposi sarcoma [100%], whereas all cases of hemangioma, angiosarcoma, hemangioendothelioma and vascular transformation of lymph nodes were negative for this antigen. Immunohistochemistry for HHV-8 is a characteristic immunohistochemical marker of Kaposi sarcoma and considered as a very useful tool for differentiation between Kaposi sarcoma and other vascular lesions

Lack of evidence of cytomegalovirus infection in patients with HIV-negative castleman's disease: immunohistochemistry analysis

Castleman's disease [CD] is a rare atypical lymphoproliferative disorder. The pathogenesis of CD is still not clear. The aim of this study is to evaluate the possible involvement of cytomegalovirus [CMV] in the pathogenesis of CD. Immunohistochemistry for CMV was performed on archival formalin-fixed, paraffin wax embedded biopsy specimens from 25 cases of CD without human immunodeficiency virus [HIV] infection at The Toronto General Hospital, University Health Network [Toronto, Canada], King Abdulaziz University Hospital [KAUH] and King Faisal Specialist Hospital and Research Centre [KFSHRC], Jeddah, Saudi Arabia]. The clinical histories were reviewed. Pathology sections [4 micro m] were stained using CMV monoclonal antibody [NCL-CMV pp65]. The assays were performed at the Department of Pathology, KAUH in 2008. The age range was 16-90 years. There were 14 males and 11 females. Twenty-one patients had the localized form of CD and 4 patients had the multicentric form. Microscopic evaluation did not show any evidence of CMV inclusion. All of the cases show negative staining for CMV immunohistochemistry. CMV is unlikely to play a significant role in the pathogenesis of cases of HIV-negative CD. These results are consistent with the rare available reports in the literature that discuss this relation

role of HHV-8 in the pathogenesis of HIV negative castleman's disease: imunohistochemistry analysis

Castleman's disease [CD] is a rare atypical lymphoproliferative disorder that is morphologically and clinically heterogeneous and is associated with a risk of developing malignant lymphoma. The pathogenesis of CD is still not clear. The aim of this study is to evaluate the possible involvement of human herpcsvirus-8 [HHV-8] in the pathogenesis of CD. Immunohistochemistry for HHV-8 was performed on archival formalin- fixed, paraffin wax embedded biopsy specimens from 25 cases of CD without human immunodeficiency virus [HIV] infection at The Toronto General Hospital, University Health Network [Toronto, Canada], King Abdulaziz University Hospital and King Faisal Specialist Hospital and Research Centre [Jeddah, Saudi Arabia]: The clinical histories were reviewed. Pathology sections [4 micro m] were stained using mouse monoclonal antibody [NCL-HHV8-LNA], which is specific for human herpesvirus type 8 latent nuclear antigen-1 [LNA-1]. The assays were performed at the Department of Pathology, KAUH, Jeddah, KSA in 2007. The age range was 16-90 years. There were 14 males and 11 females. Twenty-one patients had the localized form of CD and 4 patients had the multicentric form. Only one of the 25 cases [4%] showed positive nuclear staining. HHV-8 is unlikely to play a significant role in the pathogenesis of the large majority of cases of HIV-negative CD. This is in contrast to the reported involvement of HHV-8 in HIV-positive CD

Primitive neuroectodermal tumor of the ovary

A 31-year-old woman presented to King Abdulaziz University Hospital complaining of an abdominal pain and a rapid increase in abdominal girth. An ultrasound and MRI, revealed a huge cystic ovarian mass without ascites. Ovarian tumor markers were all within normal range. Exploratory laparotomy showed huge right ovarian mass with omental mass. Frozen section from the omentum showed metastatic malignant neoplasm. Total abdominal hysterectomy was carried out with bilateral salpingooophorectomy and omentectomy with residual tumor of less then one centimeter. Final pathology assessment showed primitive neuroectodermal tumor arising from the right ovary. She received post- operative chemotherapy. Four months later she had recurrence and was given second line chemotherapy, but she did not respond and died 15 months after the diagnosis due to obstructive uropathy

Lack of evidence of Epstein-Barr virus infection in patients with Castleman's disease molecular genetic analysis

Epstein-Barr virus [EBV] infection is associated with a diverse group of malignancies and many lymphoproliferative disorders. Castleman's disease [CD] is atypical lymphoproliferative disorder. The role of EBV in the pathogenesis of CD is not clear yet. The objective of this study is to investigate the EBV status in CD. We searched medical records for cases of CD at the Toronto General Hospital, Toronto, Canada and King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Twenty cases were found. The presence of EBV was analyzed using polymerase chain reaction. Polymerase chain reaction were performed at the Department of Pathology and Laboratory Medicine, Toronto General Hospital. The study started in 2001 and completed in 2005. The age range was 16-90 years. Seventeen patients manifested the localized form of CD. There were 11 males 9 females. Epstein-Barr virus genome was detected only in 2 cases; both were males and have plasma cell type. One is a localized type and the other is of a multicentric type. One patient revealed clonal rearrangement of the immunoglobulin H. The number of cases is small; however it appears that EBV is less likely to play a significant role in the pathogenesis of CD; however, it seems to be associated with clonal progression

Lack of evidence of epstein-barr virus infection in patients with castleman's disease molecular genetic analysis

Epstein-Barr virus [EBV] infection is associated with a diverse group of malignancies and many lymphoproliferative disorders. Castleman's disease [CD] is atypical lymphoproliferative disorder. The role of EBV in the pathogenesis of CD is not clear yet. The objective of this study is to investigate the EBV status in CD. We searched medical records for cases of CD at the Toronto General Hospital, Toronto, Canada and King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Twenty cases were found. The presence of EBV was analyzed using polymerase chain reaction. Polymerase chain reaction were performed at the Department of Pathology and Laboratory Medicine, Toronto General Hospital. The study started in 2001 and completed in 2005. The age range was 16-90 years. Seventeen patients manifested the localized form of CD. There were 11 males 9 females. Epstein-Barr virus genome was detected only in 2 cases; both were males and have plasma cell type. One is a localized type and the other is of a multicentric type. One patient revealed clonal rearrangement of the immunoglobulin H. The number of cases is small; however it appears that EBV is less likely to play a significant role in the pathogenesis of CD; however, it seems to be associated with clonal progression