Gastrointestinal stromal tumors (GISTs): a pathology view point.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas, or leiomyosarcomas, are now classified as GISTs based on histology, immunohistochemistry, and molecular study. They originate from the stem cells that differentiate toward the pacemaker cell (Interstitial cell of Cajal). Prognostic factors have been identified for GISTs and include tumor size and mitotic rate. Surgery is the standard treatment for resectable GISTs. Metastatic and inoperable GISTs should be considered the medication with tyrosine kinase inhibitor (imatinib mesylate), which inhibits the c-kit receptor. The role of the pathologist in the differential diagnosis of GISTs, as well as in the assessment of the malignant potential of the tumors, is becoming increasingly important in influencing decisions regarding clinical management of GISTs. The present paper reviews the literature of GISTs and emphasizes on the field of the pathologist's work.

Revision of gastrointestinal mesenchymal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal (GI) tract. The advent of target therapy (imatinib mesylate) for GISTs increases the importance of pathologic diagnosis. The previous diagnosis with smooth muscle tumor (leiomyoma or leiomyosarcoma) and nerve sheath tumor (schwannoma) become GISTs after the study with CD117 immunohistochemistry accompanying conventional histologic study in many series. OBJECTIVE: To identify the incidence of GISTs in the patients who were previously diagnosed with smooth muscle or nerve sheath tumors. The histology and immunoreactivity of both newly found and previously diagnosed with GISTs are also studied MATERIAL AND METHOD: A retrospective database identified all patients seen from 1998 to 2006. Patients with mesenchymal tumors of the GI tract and intraabdominal extragastrointestinal tract were selected, 53 cases in total. Clinical and pathological data, treatment, and outcome were analyzed RESULTS: After revision, the total number of GISTs is 42 cases. There were 33 cases previously diagnosed with leiomyosarcoma that became the diagnosis with GISTs (31 cases or 93.9%), due to CD117 positivity. Most of GISTs cases had spindle cell type (26 cases, 61.9%) and only the colon and omentum had predominant mixed cell type. CONCLUSION: GISTs are the most common mesenchymal neoplasm of the stomach and small intestine and are relatively less frequent at other gastrointestinal sites. An increasing awareness of their histologic, immunophenotypic, and molecular features coupled with an evolving understanding of their histogenesis is facilitating our ability to identify these tumors.

Combined liver-kidney transplantation in a patient with acute liver failure coexisting with acute renal failure.

Acute renal failure (ARF) is common among patients with liver failure awaiting liver transplantation due to the increased waiting time for available liver grafts and extended survival from improved intensive care. The role of combined liver and kidney transplantation (LKT) in this situation is quite controversial. A case of acute liver failure (ALF) complicated with ARF is reported. Non-A, non-B hepatitis was the cause of ALF. He had hemodialysis for one month before transplantation. Combined LKT was performed because of prolonged pre-transplant hemodialysis and the potential of irreversible renal failure. Severe impairment of both native kidneys was confirmed by renal scan at 6 months after transplantation. Combined LKT may be needed for patients with acute liver failure complicated with prolonged acute renal failure.

Fluorescence in situ hybridization method in isolated single nuclei extracted from paraffin-embedded hepatocellular carcinoma tissues.

BACKGROUND: Genetic analysis using the fluorescence in situ hybridization (FISH) method applied to intact tissue sections of formalin-fixed paraffin embedded (FFPE) tissue is well known to be relatively difficult. The frequent technical problems include unsuccessful hybridization as a result of poor probe penetration, excessive probe requirement, excessive background, auto-fluorescence, and overlapping or incomplete nuclei. These problems lead to absence or insufficiency of fluorescent signals, resulting in an inaccurate analysis. Formalin-fixed paraffin embedded tissue can be analyzed either as intact tissue sections or as a suspension of disaggregated, but intact, nuclei. Intact tissue sections have the advantage of preserved tissue architecture and morphology but have the intrinsic disadvantage of poor probe penetration, overlapping or incomplete nuclei and auto-fluorescence, accordingly reducing the accuracy of fluorescent signals evaluation. OBJECTIVE: To present the effective FISH method applied to isolated of single nuclei and the procedures for isolation of a single nuclei from formalin-fixed paraffin embedded tissues of hepatocellular carcinoma. MATERIAL AND METHOD: Ten paraffin-embedded blocks of hepatocellular carcinoma tissues from the department of pathology, Ramathibodi hospital, Thailand were studied. Isolated single nuclei were extracted from 10-microm sections of paraffin-embedded blocks of hepatocellular carcinoma tissue and hybridized with alpha-satellite centromeric DNA enumeration probes for chromosomes X (CEP X, spectrum green) and satellite III for chromosomes Y (CEP Y spectrum orange). The signal of at least, 200 interphase nuclei were counted from each specimen. RESULTS: The efficacy of this method has been evaluated in 10 formalin-fixed paraffin embedded tissue of hepatocellular carcinoma. The results showed bright, planar and an easy to score signal. CONCLUSION: FISH procedure described here is particularly suitable for retrospective studies of genetic aberration applied to formalin-fixed paraffin embedded tissues.

Dysplastic nodules and small primary carcinoma of the liver: a study detecting the early morphological changes during hepatocarcinogenesis.

OBJECTIVE: Detect the early histological changes relating to human hepatocarcinogenesis in three nodular hepatocellular lesions. MATERIAL AND METHOD: Three cases of dysplastic nodules and one of small hepatocellular carcinoma were obtained from the authors' surgical-pathology file during 2000-2005 for a histopathological study in relevance to the early changes during hepatocarcinogenesis by employing hematoxylin and eosin stain, as well as some immunohistochemical staining. RESULTS: One nodular hepatocellular lesion, diagnosed as a complex lesion of focal nodular hyperplasia contained a microscopic focus (1.5 mm in diameter) of combined hepatocellular and cholangiocarcinoma. CONCLUSION: The small dysplastic hepatocytes subjected to neoplastic transformation combined hepatocellular and cholangiocarcinoma and are the precursorial cells of hepatocellular carcinoma. Chronic viral hepatitis B or C, aflatoxin B, and nitrosamine(s), as well as some nodular hepatocellular lesions share distinct roles in the complex process of hepatocarcinogenesis pertaining to this Southeast Asian country.

Combined hepatocellular and cholangiocarcinoma: CT findings with emphasis on multiphasic helical CT.

OBJECTIVE: To describe CT findings of patients with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) in correlation with clinical data and histopathological results. MATERIAL AND METHOD: Ten from 31 cases whose CT study was available were reviewed retrospectively in the aspect of imaging findings, clinical data, and pathological results. RESULTS: Most of the tumors were hypodense solitary mass with gradually enhanced after contrast administration. Bile duct dilatation was observed in two cases. The overall CT findings were more similar to CC rather than HCC despite the pathological result showing predominant HCC component. Serum alpha-fetoprotein level was normal or mildly elevated while an elevated concentration of carbohydrate antigen 19-9 was observed. Hepatitis profiles showed positive to hepatitis B virus infection in four cases and hepatitis C virus infection in one case. CONCLUSION: The diagnosis of combined HCC-CC should be considered if the tumor has similar findings to CC without bile duct dilatation on cirrhotic liver and the patient has normal or low rising of the AFP level with or without elevated CA 19-9 level. In non-cirrhotic liver, the finding is non-specific.

Failure of hepatitis B surface antibody to protect acute fulminating hepatitis in a renal transplant recipient.

A 58-year-old man who had a living-related kidney transplantation (KT) 13 years ago and had received a double-dosage course of hepatitis B virus (HBV) vaccination prior to KT developed acute liver failure. An exhaustive work-up for the cause of acute liver failure revealed that HBsAg was negative but anti-HBs and anti-HBcAbs were positive. HBV DNA was 535,000 copies/ml. The strongly positive staining of HBsAg and HBcAg of liver biopsy was shown by immunohistochemistry examination. HBV harboring surface mutant of hepatitis B surface gene was thought to be the cause of acute fulminant hepatitis despite the presence of protective immunity to wild-type HBV. The patient expired from acute liver failure even though an antiviral drug was started promptly. This is the first case report of liver biopsy suggestive of acute fulminating HBV that developed in a long-term kidney recipient despite the presence of high anti-HBsAb titer.

Bilateral leiomyoma of epididymides.

Leiomyoma is a relatively uncommon neoplasm of the epididymis derived from smooth muscle cells. A case of primary leiomyomas simultaneously occurring in both epididymides is reported in a 58-year-old man, clinically presenting painless intra-scrotal masses. The examination of the epididymis characterizes clinically by a firm solid, well-circumscribe mass, and histological spindle cells arranged in interlacing bundles with varying admixtures of fibrous and hyalinized connective tissue. Clinical, histopathologic and immunohistopathologic features, with briefly reviewed relevant literatures describing 7 cases of bilateral leiomyoma of epididymides are discussed. The patients with the mean age of 56.6 years (range 47-62 years) had epididymal mass measuring 5 to 75 millimeters (mean 21.3 millimeters). This is the first reported description of bilateral leiomyoma of epididymides in Thailand.

Inflammatory bowel disease in Thai children: presentations and outcomes of treatment.

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.

Brunner's gland adenoma: a report of two cases.

Brunner 's gland adenoma is a very rare benign tumor of the duodenum. Only two cases of the adenoma have been in the file of the surgical pathology unit of Ramathibodi Hospital since 1992 and presented in this communication. The tumor is capable of producing a variety of clinical manifestations. Presently, endoscopic study plays an important role in both detection and diagnostic biopsy. Local excision, either by endoscopy or surgery is the main treatment in symptomatic cases. Ductal malignancy on top of Brunner's gland adenoma was described in one from estimated 200 recorded cases in the English literature since 1835.

Concurrent chromomycosis and aspergillosis of the maxillary sinus.

The authors describe a rare case of an infection of both the chromomycosis and aspergillosis of the maxillary sinus in an immunocompetent 72-year-old female who presented with progressive visual loss and dull aching pain of the left eye. Sinuscopy of the left maxillary sinus showed swelling of the mucosa with clay-like materials. Biopsy from the left maxillary sinus showed the typically characteristic morphology of chromomycosis and culture from sinus tissue which yielded Aspergillus. The patient responded to a combination therapy of surgical excision and antifungal agent.