Unique hepatic imaging features in a patient with nodular regenerative hyperplasia of the liver associating with systemic lupus erythematosus.

Nodular regenerative hyperplasia (NRH) of the liver, characterized by regenerative nodules distributed throughout the liver in the absence of fibrosis, is a rare but important complication of systemic lupus erythematosus (SLE). The main consequence of NRH is non-cirrhotic portal hypertension. We describe a female patient who had immune thrombocytopenia in association with elevated liver enzymes and evidence of portal hypertension as initial manifestations of SLE. Computed tomographic scan and magnetic resonance imaging of the liver in this patient showed enhancing periportal tubular structures distributed throughout the liver. The diagnosis of NRH was eventually disclosed by transcutaneous needle liver biopsy. The pattern of radiological abnormality in this patient has not been described previously in NRH. In addition, we believe this is a first reported case of SLE presenting with immune thrombocytopenia in association with NRH.

Oesophageal tuberculosis mimicking oesophageal carcinoma.

Tuberculous involvement of the oesophagus is rare, and is usually caused by direct spread from adjacent afflicted structures. We report an 83-year-old male patient with oesophageal tuberculosis secondary to tuberculous mediastinal lymphadenitis who presented with non-specific symptoms of anorexia and lethargy. Upper gastro-intestinal endoscopy revealed an ulcerative tumour-like lesion in the mid-oesophagus suggesting oesophageal carcinoma. Repeated endoscopic biopsies revealed a non-specific acute-on-chronic inflammation consisting of non-caseating granulomas, with no evidence of malignancy. Endoscopic ultrasonography demonstrated that the oesophageal lesion was secondary to direct extension of mediastinal lymphadenopathy. The diagnosis of tuberculosis was eventually confirmed by histological and microbiological analysis of a surgically excised cervical lymph node. The patient responded promptly to treatment with antituberculous drugs. We suggest that oesophageal tuberculosis has to be kept in mind in the differential diagnosis of oesophageal ulcerohypertrophic lesions.

Intestinal tuberculosis in a regional hospital in Hong Kong: a 10-year experience.

OBJECTIVE: To study the clinical and pathological characteristics of patients with intestinal tuberculosis. DESIGN: Retrospective study. SETTING: United Christian Hospital, Hong Kong. PATIENTS: Patients with intestinal tuberculosis diagnosed between January 1995 and December 2004 inclusive. RESULTS: The median age of the 13 male and 9 female patients was 53 years (range, 12-81 years). Nineteen (86%) had a definitive diagnosis of intestinal tuberculosis confirmed by the presence of caseating granulomas and/or acid-fast bacilli in histological specimens. In three (14%) the diagnosis was based on histology revealing non-caseating granulomas and a positive response to anti-tuberculous treatment. Common symptoms included abdominal pain (82%), diarrhoea (55%), weight loss (55%), and fever (45%). Three (14%) of the patients were complicated by intestinal obstruction, and another two (9%) had intestinal perforation. Four (18%) had concomitant active pulmonary tuberculosis. The most frequently involved site was the ileocaecal region, which was affected in 19 (86%) patients. Other sites included the jejunum, ascending and sigmoid colon. The diagnosis of intestinal tuberculosis was facilitated by examination of colonoscopic biopsy specimens (11 patients), and by examination of resected surgical specimens in the remainder. Two patients died from terminal malignancy. The remainder completed anti-tuberculous therapy and responded satisfactorily. CONCLUSIONS: The diagnosis of intestinal tuberculosis is difficult due to the lack of specific signs or symptoms. Colonoscopy with ileoscopy are useful tools in the search for colonic and terminal ileal tuberculosis. Surgical exploration is reserved for equivocal cases and for those who present as emergencies.

Multicentric osteosarcoma presenting as retrobulbar mass: a diagnostic enigma.

Osteosarcoma is the most common primary malignant bone tumor of children and adolescents. It often presents as a solitary lesion; multicentric osteosarcoma with synchronous lesions occurring at multiple skeletal sites is very rare. We report a 9-year-old boy with multicentric osteosarcoma who presented with a left retrobulbar non-sclerotic mass. The multiple lesions in bone were mostly non-sclerotic on radiological examination except for a single lesion in the left tibia. Biopsy of the retrobulbar mass showed an unclassifiable poorly differentiated malignant tumor. Marrow aspiration smears showed many large, often segregated, round cells that expressed NB84a. However, trephine biopsy showed the formation of tumoral osteoid by the malignant cells, finally permitting the definitive diagnosis of osteosarcoma to be made. A hypertetraploid clone with complex structural abnormalities was demonstrated by cytogenetic study.

Recurrent variceal bleeding in a young woman.

Congenital hepatic fibrosis is an uncommon fibrocystic disorder affecting the intrahepatic bile ducts. It has autosomal recessive inheritance. The main consequence of this condition is portal hypertension and it is often misdiagnosed as cirrhosis. Patients with congenital hepatic fibrosis usually present during childhood or early adolescence with oesophageal variceal bleeding. Portosystemic shunt surgery is the treatment of choice for these patients as the risk of postoperative hepatic encephalopathy is low. We report a patient with congenital hepatic fibrosis who presented with oesophageal variceal bleeding at the age of 16 years, initially misdiagnosed as having cryptogenic liver cirrhosis. The patient experienced two further episodes of oesophageal variceal bleeding in subsequent years. She eventually underwent portosystemic shunt surgery. One year after the operation, the shunt remained patent on Doppler ultrasonography, and there had been no further episodes of variceal bleeding post-surgery.

Hepatic myospherulosis complicating portal vein embolisation.

AIMS: Myospherulosis is a rare condition characterised by sac-like structures containing spheroid bodies in cysts or cystic spaces in the tissue. This condition has not previously been reported in the liver. The association with previous portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil and the proposed mechanism of pathogenesis are discussed. METHODS: Samples from 8 patients treated by hepatectomy after portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil were retrieved from the archives of the United Christian Hospital, Hong Kong. The histological specimens were reviewed. A panel of histochemical and immunohistochemical stains was used. RESULTS: All cases showed hepatic myospherulosis within the veins. The veins were denuded of endothelium, which was replaced by granulation tissue and fibrous tissue with a lymphoplasmacytic infiltrate. Foreign body-type giant cells (six cases) and eosinophilic infiltrates (seven cases) were noted in most cases. Both parent bodies and endobodies were stained red by Papanicolaou and Masson's trichrome and stained blue by solochrome cyanine. The endobodies showed immunoreactivity towards glycophorin A. They were negative for Alcian blue, periodic acid Schiff, Grocott, and Ziehl-Neelsen stains. CONCLUSIONS: The endobodies of myospherulosis may be misdiagnosed as fungi or algae by the unwary. The clinical history, intravascular location, lack of staining with periodic acid Schiff and Grocott stains, and positive glycophorin A staining are generally sufficient for a confident diagnosis of myospherulosis.

Subacute hepatic failure after the perinatal period with haemochromatotic siderosis at the age of 11 months: an unusual perspective on neonatal haemochromatosis.

UNLABELLED: Neonatal haemochromatosis is a rare disease characterized by the early onset of liver failure, a rapidly deteriorating clinical course and high mortality. An unusual case is presented of subacute hepatic failure in which autopsy findings at the age of 11 mo showed a haemochromatotic pattern of siderosis. Despite the similarity in the pattern of iron distribution to neonatal haemochromatosis, the clinical course was highly atypical in that the infant had later and milder presentation at 1 mo of age and slow progression into liver failure. This case illustrates the heterogeneous nature of the haemochromatotic phenotype in newborns and infants. CONCLUSION: The entity "neonatal haemochromatosis" may reflect a spectrum of diseases with diverse aetiologies. Fulminant liver disease in the newborn period can also result in similar pattern of iron distribution.

Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients.

The Hong Kong Chinese population has an unusually high incidence of colorectal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, blood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10 females (26.6%). Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours. The incidence of MSI increased significantly with decreasing age at cancer diagnosis. For patients aged 30 to 49, MSI tumours were located mainly at the proximal colon. However, for exceptionally young patients (<30 years), MSI tumours tended to be at the distal large bowel. This observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, and a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young colorectal cancer patients and their families.

Interdigitating dendritic cell tumor of the testis: a novel testicular spindle cell neoplasm.

Interdigitating dendritic cell tumor is an extremely rare neoplasm that mainly occurs in lymph nodes. An example of such a tumor in the testis, a hitherto unreported site, is described. Grossly, the tumor was light tan with a uniform solid appearance, replacing virtually the entire testis. Microscopically, it was formed by whorls and fascicles of spindle cells intermingling with small lymphocytes. Such a histologic appearance can, however, mimic a wide variety of other tumors and tumor-like lesions, among which mesenchymal sarcoma, spindle cell carcinoma, follicular dendritic cell tumor, and inflammatory pseudotumor are the main differential diagnoses. Immunohistochemical studies showed that the spindle tumor cells were strongly and diffusely positive for S-100 protein and vimentin. They were also focally positive for CD68 and CD4, but were uniformly negative for leukocyte common antigen, CD1a, CD3, CD20, CD21, CD23, CD34, CD35, actin, desmin, HMB45, cytokeratins, and placental alkaline phosphatase. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes, with abundant rough endoplasmic reticulum and mitochondria in their cytoplasm. An in situ hybridization study for Epstein-Barr virus was negative. The pathologist should be aware of such an entity and consider it in the list of differential diagnoses for unusual spindle cell lesions with a significant background population of small lymphocytes. However, because of its nonspecific histologic appearance, additional immunohistochemical and electron microscopic studies are generally required for its definitive diagnosis.

Metanephric adenofibroma: report of a case and review of the literature.

The recent recognition of a variety of pediatric renal tumors of different biologic behavior places an ever-increasing demand on the surgical pathologist for an accurate diagnosis. Although metanephric adenofibroma is one of the rarest benign renal tumors, the clinical importance of correctly diagnosing it cannot be overemphasized because it can potentially be mistaken as Wilms' tumor. We describe the clinical, radiologic, and pathologic features of a case of metanephric adenofibroma and discuss its differential diagnosis. The neoplasm was composed of two discrete components: a major fibroblastic element and a minor immature epithelial element. The latter formed a small nodule beneath the renal capsule, which could barely be detected by magnetic resonance imaging. This subcapsular nodule, however, was slightly soft and tan and was distinctly different from the white, whorled cut surface of the main tumor. It was formed by closely packed small immature epithelial cells in a slightly edematous background, which was histologically identical to metanephric adenoma and closely resembled epithelial Wilms' tumor. Unlike Wilms' tumor, however, the epithelial cells were very bland with no mitoses. The main bulk of the tumor was formed by spindle fibroblastic cells that were cytologically similar to the spindle cells in congenital mesoblastic nephroma. The tumor, however, was well demarcated without the irregular infiltrating edges of congenital mesoblastic nephroma. In contrast to the randomly distributed epithelial element throughout the stromal component in previous reported cases of metanephric adenofibroma, our finding of the exceedingly small and discrete epithelial component expands the known histologic spectrum of the disease. In addition, the presence of such minute epithelial nodule underscores the importance of diligent pathologic examination and careful sampling of tissue for histologic examination.

Clear cell carcinoid tumor of stomach. A variant mimicking gastric xanthelasma.

We report a rare case of gastric carcinoid composed entirely of clear cells with foamy cytoplasm. The patient was a 75-year-old Hispanic woman with atrophic fundic (oxyntic) gland gastritis leading to hypochlorhydria, secondary hypergastrinemia, endocrine cell hyperplasia, and multiple gastric carcinoids. Grossly, the lesion was yellow and distinct from other carcinoids in the gastric mucosa, mimicking gastric xanthelasma. Histologically, the tumor consisted of uniform clusters of polygonal cells with foamy cytoplasm. The formation of cell packets and abundant vascular stroma provided clues to its neuroendocrine nature. This was confirmed by immunoreactivity for chromogranin A and the demonstration of dense core granules ultrastructurally.

Colorectal carcinoma in Hong Kong: epidemiology and genetic mutations.

The incidence of colorectal carcinoma is rising at an alarming pace in Asian urban societies such as Hong Kong. Detailed examination of the epidemiological pattern and genetic mutation of colorectal cancer in the Hong Kong Chinese population is overdue. We compared the reported age incidence of colorectal carcinoma in Hong Kong with that of Scotland and other countries. Hong Kong showed a much higher incidence of colorectal carcinoma among the young age groups. By comparison with other countries, this raised incidence among the young appeared to be related to southern Chinese societies. The recent dramatic rise in colorectal cancer in Hong Kong was largely attributable to an increase in the over 50 years age group, while the young incidence remained unchanged. We also defined the mutation spectrum of p53 and Ki-ras in 67 unselected cases by direct DNA sequencing. Interestingly, insertion/deletion mutations in p53 from colorectal carcinoma in Hong Kong showed a significantly higher frequency (17.2%) than the Scottish data (0%) and the world database (6.6%), although the overall frequency of p53 mutation (43%) in Hong Kong was similar to others. The high incidence of colorectal carcinoma in young people and the raised proportion of frameshift mutations in p53 encourage further search for a genetic basis for susceptibility to this disease in the Hong Kong Chinese population.

Lymphoepithelioma-like carcinoma of the skin.

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Lymphoepithelioma-like carcinoma of the thyroid gland: lack of evidence of association with Epstein-Barr virus.

Lymphoepithelioma-like carcinomas (LELC) occurring in sites derived from the primitive pharynx and foregut have been reported to show a strong association with Epstein-Barr virus (EBV), especially in the Oriental population. Primary lymphoepithelioma-like carcinoma of the thyroid is an extremely rare neoplasm which has been known under many different names, such as intrathyroidal epithelial thymoma, primary thyroid thymoma, carcinoma of the thyroid showing thymoma-like features, and carcinoma showing thymus-like differentiation (CASTLE). We report one such case in a Chinese woman, whose tumor was negative for EBV by in situ hybridization technique. This finding suggests that LELC of the thyroid may be biologically different from other LELCs, and that detection of EBV may aid in diagnosis when the LELC presents initially in lymph nodes or other metastatic sites.

Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis.

Pituitary adenomas may cause significant difficulties in histological diagnosis when presenting in unusual sites either as extension from an intrasellar lesion or as ectopic tumor. Three such cases, involving the sinonasal tract are described herein, and the differential diagnoses are discussed. Two of them were invasive intrasellar macroadenomas that presented as unilateral nasal polyp, and one was an ectopic pituitary adenoma involving the sphenoid sinus. There was notable cellular atypia in two cases, with nuclear pleomorphism, giant cells, chromatin clumping, and distinct nucleoli, leading to serious consideration of the possibility of poorly differentiated carcinoma. In none of the cases was the diagnosis of pituitary adenoma suspected clinically. The clues to diagnosis were an endocrine growth pattern comprising tumor cells arranged in packets, ribbons, or rosettes, with prominent delicate vascularized stroma; a high index of suspicion; and immunohistochemical showing of neuroendocrine markers and pituitary hormones in the tumor cells. A correct diagnosis is important because in contrast to neuroendocrine carcinoma as a whole or to poorly differentiated carcinoma, pituitary neoplasms have a much more favorable prognosis and a low metastatic potential.

Germ cell tumour as a diagnostic pitfall of metastatic carcinoma.

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.

Inflammatory cell-rich gastrointestinal autonomic nerve tumor. An expansion of its histologic spectrum.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon neoplasm of the gastrointestinal tract. Its histologic appearance is similar to other gastrointestinal stromal tumors. Ultrastructural demonstration of neural differentiation is required for its definitive diagnosis. Recently, we encountered two examples of GAN tumor that occurred in the body of the stomach and the cervical esophagus; the latter site has never been reported previously. These tumors showed unequivocal evidence of neural differentiation ultrastructurally, confirming the diagnosis of GAN tumor. Histologically, they were composed of swirling fascicles of spindle cells as well as a minor component of epithelioid cells, similar to that described previously. In addition, a cuff of lymphoid cells was noted at the peripheral part of both tumors and a scattering of mature plasma cells, lymphocytes, and foam cells was intermingled with the tumor cells. Such histologic features have not been described hitherto and can potentially be misinterpreted as features of inflammatory pseudotumor, inflammatory fibrosarcoma, or follicular dendritic cell tumor. There is a lack of CD34 expression in both tumors, but it would be premature to draw any conclusions about the potential usefulness of this observation.

Paclitaxel-induced cardiotoxicity. An ultrastructural study.

The ultrastructural appearance of the myocardium in a fatal case of paclitaxel-induced cardiotoxicity is reported, which includes swelling of the sarcoplasmic reticulum, loss of myofibrils, and accumulation of lipofuscin as well as laminated myelinoid figures. Such changes are very similar to those seen in anthracycline-induced cardiotoxicity and may suggest a pathogenetic final common pathway. While endomyocardial biopsy is a recognized means of monitoring anthracycline-induced cardiotoxicity, whether more liberal use of endomyocardial biopsy can prevent fatal cases of paclitaxel-induced cardiotoxicity needs to be further assessed.