Inflammatory myofibroblastic tumour of the duodenum.

Inflammatory myofibroblastic tumours (IMTs) of the duodenum and head of the pancreas are rare. They are of probable immunological aetiology and preoperatively indistinguishable from adenocarcinomas of the pancreatic head. We describe a patient with duodenal IMT and gastric outlet obstruction, and present a review of pancreatic head and duodenal IMTs in the literature. IMTs of the pancreatic head present as obstructive jaundice, while those of the duodenum present as gastric outlet obstruction. Surgery is the primary modality of treatment. Adjuvant chemotherapy and radiotherapy are controversial and reserved for incomplete resections and IMTs of a pathologically aggressive nature. Otherwise, recurrence is uncommon and surgery curative.

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour.

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.

Prospective evaluation of transient elastography for the diagnosis of hepatic fibrosis in Asians: comparison with liver biopsy and aspartate transaminase platelet ratio index.

BACKGROUND: Transient elastography (TE) is a reliable non-invasive predictor of hepatic fibrosis, but data on TE in Asians are limited. AIM: To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index). METHODS: One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F >or= 2) and cirrhosis (F4). RESULTS: Predominant aetiologies were hepatitis B (48%), non-alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter-costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis (r = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779-0.932) for TE and 0.673 (95% CI 0.568-0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857-0.990) for TE and 0.626 (95% CI 0.437-0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively. CONCLUSIONS: Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter-costal space. TE is superior to APRI for non-invasive diagnosis of hepatic fibrosis and cirrhosis.

Pathologic, radiologic and PET scan response of gastrointestinal stromal tumors after neoadjuvant treatment with imatinib mesylate.

AIM: The aim of this study is to review the radiologic, PET scan and pathologic response and the outcome of patients with advanced GIST treated with neoadjuvant IM followed by surgical resection. MATERIALS AND METHODS: We report a case and review 36 patients reported in MEDLINE with advanced GIST treated with neoadjuvant IM followed by surgical resection. RESULTS: Thirty-seven patients with a median age of 56 years (range, 32-76 years) at presentation were treated with neoadjuvant IM. Radiologic response accurately predicted pathological response in 31/36 patients, whereas PET scan was accurate in predicting treatment response in only 6/23 patients. CONCLUSION: This study demonstrates that the pathologic response of GIST to IM is usually incomplete and does not correlate with the complete response seen on PET scan. This finding suggests that surgical resection will continue to play a vital role in the treatment of patients with advanced disease responding to IM treatment.

Primary retroperitoneal mucinous cystadenocarcinoma in a male patient.

Primary retroperitoneal mucinous cystadenocarcinomas (PRMCs) are rare. This is the first reported case in the literature in English of PRMC in a man. The 64-year-old man presented with a large retroperitoneal cystic tumour measuring 24 x 20 x 16 cm3, which was removed intact. Areas ranging from a benign mucinous cyst to borderline mucinous tumour to mucinous cystadenocarcinoma were observed on microscopy. Strong patchy staining for cytokeratins 7 and 20 and strong diffuse staining for MUC2 and MUC5AC core peptides, similar to staining patterns in ovarian mucinous tumours, were shown in the benign and atypical epithelium. Staining for CA19.9 and carcinoembryonic antigen was also shown by both components. The theory of its origin from the mucinous metaplasia of peritoneal (mesothelial) inclusion cysts, rather than from ectopic ovarian tissue or ovarian teratomas, is supported by the occurrence of such a tumour in a male patient.

An unusual cause of granulomatous inflammation: eosinophilic abscess in Langerhans cell histiocytosis.

Eosinophilic abscess inciting a granulomatous response has rarely been reported and appears not to have been described in the setting of a neoplasm. In this report, a case is described where a granulomatous response occurred around eosinophilic abscesses in a patient with Langerhans cell histiocytosis, an association which has not previously been documented. On histology, the excised lymph node showed the presence of eosinophilic abscess and necrosis surrounded by granulomas, which in turn were surrounded by Langerhans cells, a feature confirmed on immunohistochemistry. Although rare, this case highlights the importance of careful examination of eosinophilic abscess with granulomatous inflammation in order to exclude an underlying neoplasm.

Incidental hypoglobus: primary amyloidosis of the superior rectus.

A 69-year-old man who presented with incidental hypoglobus was found to have an isolated superior rectus mass. Diagnosis of primary amyloidosis of superior rectus was made on incisional biopsy and negative systemic work-up. This is an unusual manifestation and site for amyloidosis and should be a differential of any extraocular muscle mass.

Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility?

AIMS: To assess inter/intraobserver variability in the interpretation of a series of digitised images of columnar cell lesions (CCLs) of the breast. METHODS: After a tutorial on breast CCL, 39 images were presented to seven staff pathologists, who were instructed to categorize the lesions as follows: 0, no columnar cell change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5, DCIS. Concordance with the tutor's diagnosis and degree of agreement among pathologists for each image were determined. The same set of images was re-presented to the pathologists one week later, their diagnoses collated, and inter/intraobservor reproducibility and level of agreement for individual images analysed. RESULTS: Diagnostic reproducibility with the tutor ranged from moderate to substantial (kappa values, 0.439-0.697) in the first exercise. At repeat evaluation, intraobserver agreement was fair to perfect (kappa values, 0.271-0.832), whereas concordance with the tutor varied from fair to substantial (kappa values, 0.334-0.669). There was unanimous agreement on more images during the second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest agreement was seen for CCC with cytological atypia. CONCLUSIONS: Interobserver and intraobserver agreement is good for DCIS, but more effort is needed to improve diagnostic consistency in the category of CCC with cytological atypia. Continued awareness and study of these lesions are necessary to enhance recognition and understanding.

Clinical usefulness of endoscopic ultrasonography with or without fine needle aspiration in the diagnosis and staging of pancreatic carcinoma.

INTRODUCTION: The aims of this study was to show the accuracy and clinical usefulness of endoscopic ultrasonography (EUS) with EUS-guided fine needle aspiration (FNA) in the diagnosis and staging of pancreatic cancer not obvious in computed tomographic (CT) scan abdomen imaging. MATERIALS AND METHODS: Five male patients were evaluated; 4 presented with obstructive jaundice and 1 had unexplained loss of weight. The mean age was 66 years (range, 40 to 77). All had CT scan abdomen imaging which did not show any obvious pancreatic tumour. EUS with FNA was done for all cases when indicated. Surgical findings, if any, were obtained and compared to EUS findings. RESULTS: EUS easily detected the pancreatic tumour in all 5 cases. The tumour sizes detected ranged from 27 to 40 mm in diameter. These corresponded fairly accurately with that of surgical findings for all 3 who had surgery. EUS reported 3 cases with pathological lymph node involvement. All 5 cases were confirmed by FNA or surgery. EUS was also accurate in 4 cases, which reported the absence of portal vein or superior mesenteric vein invasion. Surgical documentation could not verify the fifth case. There were no complications at all from the EUS with/without FNA. CONCLUSION: This case series showed that EUS with/without FNA appears to be useful and safe in diagnosing and staging pancreatic head tumours not detectable by CT scanning.

Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in the evaluation of breast lesions.

AIMS: To evaluate the morphological features of 11 cases of breast ductal carcinoma in situ (DCIS) with spindle cells and to propose an approach to distinguish it from benign mimics. The association with neuroendocrine differentiation was also investigated. METHODS: Cases of breast DCIS with a spindle cell component diagnosed in the Department of Pathology, Singapore General Hospital, between June 1996 and January 2003, were included in the study. The histological characteristics were documented, and immunohistochemistry for neuroendocrine markers, hormone receptors, cerbB2, smooth muscle actin (SMA) and high-molecular-weight (HMW) cytokeratins, was carried out. Electron microscopy was carried out on reprocessed paraffin-embedded material in three cases. RESULTS: Of 11 women diagnosed with DCIS with spindle cells, four presented with nipple discharge, six with a breast lump, while one was discovered to have a screen detected density. The tumour size ranged from 3 to 41 mm. The proportion of spindle cells varied from 10% to 80% of the in-situ tumour cell population. Nuclear grade was low in seven cases and intermediate in four. Necrosis was observed in two cases. Architectural pattern was papillary in six cases, and mixed in the rest. Microinvasion was present in two cases, with possible microinvasion in another two. Immunohistochemistry for neuroendocrine markers synaptophysin and chromogranin showed positive reactivity for at least one marker in all but three cases; one of these latter cases demonstrated ultrastructural neurosecretory granules. Oestrogen and progesterone receptors were expressed in 10 and nine cases, respectively, while cerbB2 was positive in only one case. HMW cytokeratin immunoprofile revealed a general lack of immunostaining within the abnormal cell population; likewise, no positivity for SMA of the cellular proliferation was detected. CONCLUSIONS: Almost all DCIS lesions with spindle cells disclose neuroendocrine differentiation. Although the distinction from benign florid usual hyperplasia may pose a diagnostic histological problem, the presence of diffuse neuroendocrine expression, in conjunction with the pattern of HMW keratin profile on immunohistochemistry, supports an in-situ neoplastic process. The absence of SMA immunostaining, in conjunction with negative reactivity for cytokeratins 5/6 and 14, makes the possibility of a myoepithelial proliferation unlikely.

An unusual case of nonspecific interstitial pneumonia treated initially with surgical resection.

Nonspecific interstitial pneumonia (NSIP) has been recently described as a distinct clinicopathologic entity. We describe an unusual case of a middle-aged man who presented with exertional dyspnoea, cough, radiographic airspace opacities in the left lung and previous history of right thoracotomy for suspected right lower lobe neoplasm. Histology at that time revealed "chronic inflammation". A course of high-dose steroids was given after failure of the airspace opacities to respond to a trial of antituberculous therapy. Improvement in symptoms and radiological appearance was noted subsequently. A diagnosis of nonspecific interstitial pneumonia was made on review of the initial open lung biopsy specimen. Seven months after tailing down to maintenance low-dose steroids, the NSIP relapsed. The NSIP subsequently responded again to high-dose steroids. This case illustrates that NSIP is a difficult diagnosis, may present as a focal lung opacity initially, and may relapse after steroid dose is tailed down.

Langerhans cell histiocytosis involving the thyroid and parathyroid glands.

Langerhans cell histiocytosis (LCH) is a rare illness, and the disease afflicting the thyroid gland is very uncommon, even in the presence of multisystem involvement. In this report, we document histologically, for the first time, concurrent involvement of the thyroid and parathyroid glands by LCH. A young Chinese woman with a history of diabetes insipidus and hypogonadism underwent a total thyroidectomy for enlarged thyroid gland secondary to LCH causing airway obstruction. Microscopic examination of the excised specimen disclosed CD1a- and S-100-positive LCH cells involving the thyroid and parathyroid glands. In a patient with LCH affecting the thyroid gland, parathyroid gland disease should be suspected when the serum calcium levels are depressed in association with an inappropriate serum parathyroid hormone level, such as a normal parathyroid hormone level in this case.

Hypoglycaemia from islet cell hyperplasia and nesidioblastosis in a patient with type 2 diabetes mellitus--a case report.

INTRODUCTION: We report the first case of hypoglycaemia from beta cell hyperplasia with nesidioblastosis in an Asian adult with pre-existing type 2 diabetes. CLINICAL PICTURE: A 57-year-old Chinese woman presented with hyperinsulinaemic hypoglycaemia despite discontinuation of oral hypoglycaemic agents 4 months after diagnosis of type 2 diabetes. Preoperative portal venous sampling suggested regionalisation to the neck of the pancreas. Intraoperative ultrasound and palpation of the fully mobilised pancreas were non-localising. TREATMENT: A subtotal 85% pancreatectomy was performed with success. OUTCOME: Histology showed no evidence of tumour, but revealed islet hyperplasia and nesidioblastosis. Her diabetes was subsequently well controlled on metformin therapy. CONCLUSION: Endogenous hyperinsulinism from beta cell hyperplasia with nesidioblastosis may rarely occur in type 2 diabetics. However, this remains a diagnosis of exclusion that is confirmed only on surgical pathology. In affected individuals, preoperative portal venous sampling may be falsely localising, especially if selective sampling of the smaller peri-pancreatic veins is omitted. Definite treatment involves pancreatectomy, although the extent of surgical resection is not well established.

Lymphocytic infiltration in undifferentiated nasopharyngeal cancer.

BACKGROUND: Undifferentiated nasopharyngeal carcinoma (NPC) is characterized by prominent lymphocytic infiltration. Although the lymphoid infiltrate in NPC has been examined extensively in morphologic and immunocytochemical studies, the significance of this lymphoid infiltrate and its correlation with prognosis has been a subject of controversy for years. OBJECTIVE: To elucidate the significance of lymphoid infiltration in undifferentiated NPC. DESIGN: Evaluation of the relationship between lymphocytic infiltration in NPC and cervical lymph node status, ultrastructural examination of the lymphoid infiltrate, and assessment of lymphocytic infiltration as an independent prognosticator of regional node metastasis. MATERIALS AND METHODS: Lymphocytic infiltration was evaluated quantitatively in 20 cases of undifferentiated NPC using light microscopy. Four cases of undifferentiated NPC were processed for conventional electron microscopy. The effects of degree of lymphocytic infiltration, age, and tumor stage on cervical nodal metastasis were analysed using the logistic regression model. RESULTS: The degree of lymphoid infiltration correlated with cervical nodal metastasis (P<.001). Ultrastructural evidence of lymphocytes destroying cancer cells was seen. Lymphocytic infiltration was found to be an independent factor affecting cervical nodal metastasis (P =.02, univariate analysis; P =.03, multivariate analysis). CONCLUSIONS: The lymphoid infiltrate is beneficial in undifferentiated NPC, and its presence may deter regional metastasis of cancer cells to the cervical nodes.

Proliferative potential in nasopharyngeal carcinoma: correlations with metallothionein expression and tissue zinc levels.

Metallothionein (MT) is a cysteine-rich protein with pleiotropic functions and a high binding affinity for heavy metals. The present study was designed to examine the relationship between MT expression and tissue zinc levels in conjunction with cell proliferation in nasopharyngeal cancer (NPC). Proliferative activity in NPC was quantified by Ki67 immunolabelling and MT expression was determined by immunohistochemistry. Total zinc and subcellular zinc fractions were analysed by flame atomic absorption spectrometry. MT immunostaining was observed in the nuclei of NPC cells, with the percentage MT immunopositivity ranging from 3.0 to 59.7%. Thirteen tumours displayed weak MT staining and the remaining 11 showed moderate to strong immunostaining. There was a significant positive correlation between MT and Ki67 positivity (P = 0.0127). Tissue zinc levels were higher in NPC as compared with benign nasopharyngeal tissues (4.800 +/- 0.4610 versus 2.889 +/- 0.4045 microgram/g dry wt tissue, respectively; P = 0.0122). Nuclear zinc levels in NPC were significantly higher than levels in membrane and cytosolic fractions (mean zinc levels 1.4840 +/- 0.1489, 0.6286 +/- 0.0789 and 0.3014 +/- 0.0250 microgram/mg protein, respectively). A linear relationship was also observed between nuclear zinc levels and MT immunostaining (P = 0.0024) as well as with Ki67 immunopositivity (P = 0.0123). Our results show that MT and zinc are correlated with proliferative activity in NPC, providing further insights into the biology of this enigmatic and aggressive tumour.

Prostate tumours from an Asian population: examination of bax, bcl-2, p53 and ras and identification of bax as a prognostic marker.

Molecular studies have suggested that ethnicity may play a significant role in prostate tumorigenesis, but no information exists for groups other than Caucasian or Japanese patients. We examined 62 archival samples of prostate tumours from Asians of non-Japanese origin for the over-expression of p53, for the possible presence of mutated ras genes, for the overexpression of the bcl-2 and bax proteins, as well as directly for the presence of apoptotic cells by the TUNEL methodology. Gene lesions of both ras (0%) and p53 (3%) were rare. While bcl-2 expression was not observed in any sample, bax expression was noted in 76% of samples and was associated with a significantly worse patient prognosis both overall (P< 0.005) and specifically in Chinese patients (P< 0.02). Apoptotic cells were found in 61% of samples, and were significantly associated with the presence of bax expression (P = 0.002), but not patient survival. These results suggest that prostate tumours from non-Japanese Asians are genetically distinct from prostate tumour found in both Japanese and Caucasian patients, and that treatment modalities may need to be tailored for specific population groups.

A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial aspergillosis.

INTRODUCTION: A 62-year-old Indian male with diabetes mellitus presented with atypical, overlap features of Aspergillus hypersensitivity syndrome and obstructing bronchial aspergillosis. CLINICAL PICTURE: He was febrile and tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. TREATMENT AND OUTCOME: He responded initially to high dose steroid therapy but deteriorated subsequently from extensive mucus plugging of the bronchial tree which resulted in respiratory failure and death. He was HIV-negative. CONCLUSION: Culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs should be performed as early treatment may be life-saving.

Infiltrating lymphocytes in undifferentiated nasopharyngeal cancer lack metallothionein expression.

Metallothionein (MT) is a metal-binding protein with functional roles in cell growth, repair and differentiation. MT is reported to be differentially expressed in lymphocytes of malignant gastrointestinal lesions. The level of MT protein was examined by immunohistochemical analysis at light microscopic and ultrastructural level in infiltrating lymphocytes from 20 cases of undifferentiated nasopharyngeal carcinoma (NPC). MT expression was found to be absent in the infiltrating lymphocytes of NPC and in reactive lymphocytes of lymphoid hyperplasia in nasopharyngeal tissues. Ultrastructural examination confirmed the absence of MT immunoreactivity in the lymphoid infiltrate of NPC. On the other hand, malignant lymphoblasts of diffuse large cell lymphoma, showed MT-immunopositivity by immunoelectron microscopy. This study demonstrates a lack of MT expression in the lymphoid stroma of undifferentiated NPC, a further characteristic of its non-neoplastic nature.

Nocardiosis in patients with systemic lupus erythematosus. The Singapore Lupus Study Group.

Nocardia, a gram positive variably acid-fast aerobic bacterium is an opportunistic pathogen in immunocompromised hosts. We present 5 cases of nocardiosis in patients with systemic lupus erythematosus. We emphasize the clinical features, radiologic findings, and antibiotic sensitivity. Lung involvement was the predominant manifestation; others include brain abscess, retinitis, thyroiditis, and diaphragmatic infiltration. We describe the first cases of pulmonary nocardiosis presenting as pneumothorax and the use of fine needle aspiration cytology in diagnosing nocardial thyroiditis.