Pustular pyoderma gangrenosum: an uncommon variant which is easily misdiagnosed.

Pustular pyoderma gangrenosum is a relatively uncommon clinical form of pyoderma gangrenosum; it presents with vesiculo-pustular lesions that do not develop into frank ulceration. We report a case of a 44-year-old man with associated ulcerative colitis, who was misdiagnosed as having necrotizing fasciitis. He underwent multiple debridements and a subsequent skin grafting procedure, but without improvement. The diagnosis of pyoderma gangrenosum is often challenging because there is no defining diagnostic clinical, laboratory, or histopathological feature. A high index of suspicion is, therefore, essential to diagnose pyoderma gangrenosum clinically because failure to do so in the early stages of the disease can lead to disfigurement and even unnecessary and detrimental surgery.

Improving B mode ultrasound evaluation of breast lesions with real-time ultrasound elastography--a clinical approach.

Ultrasound elastography using the extended combined auto-correlation method of tissue elasticity allows for real-time strain image visualisation using a free-hand probe with concurrent conventional B mode imaging. Four hundred and fifteen consecutive women with 550 breast lesions confirmed on B mode ultrasound were assessed with elastography using the elasticity score. There were 119 malignant and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was 98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and that for benign lesions was 2. There was good correlation with B mode BIRADS category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8-99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions with an elasticity score of 3 were malignant. Real-time ultrasound elastography is user-friendly with a high accuracy rate, thereby improving B mode ultrasound assessment.

Clinical usefulness of endoscopic ultrasonography-guided fine-needle aspiration in the diagnosis and staging of lung cancer.

Lung cancer is the most common cause of cancer-related mortality in Singapore, and accurate staging of lung cancer is therefore of paramount importance. Several non-invasive and invasive modalities can be used to stage lung cancer. Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) is a safe procedure that is performed under conscious sedation and has a sensitivity of up to 90-98 percent in expert hands. In addition, nodal groups that are inaccessible by cervical mediastinoscopy (such as the aortopulmonary window lymph nodes) can be sampled by EUS-FNA. We present three cases in which EUS-FNA was used successfully to diagnose and stage lung cancer, thus avoiding surgery.

Kikuchi's disease: a Singapore case series.

INTRODUCTION: Kikuchi's disease is a benign form of cervical lymphadenopathy that commonly affects young adults. We report a case series from our hospital. METHODS: The clinical features of 23 cases of Kikuchi's disease diagnosed at Changi General Hospital over a seven year period are presented. The cases were identified from pathology records using the search term histiocytic necrotising lymphadenitis. RESULTS: Most of our patients (78 percent) were young women who presented with cervical lymphadenopathy. The median age was 31 years. In the 18 cases who completed follow-up at the hospital, there was spontaneous resolution of symptoms within a six-month period. One patient demonstrated seropositivity for systemic lupus erythematosus (SLE) and was initially started on steroids. However, the treatment was discontinued shortly afterwards since she did not meet the diagnostic criteria for SLE. Excision biopsy of the affected lymph node was the diagnostic method of choice. CONCLUSION: Kikuchi's disease is not uncommon in the Singaporean population. Establishing an early diagnosis is crucial since the clinical presentation can mimic tuberculous lymphadenitis or malignant lymphoma. The diagnostic method of choice is excision biopsy.

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.

Dapsone hypersensitivity syndrome masquerading as a viral exanthem: three cases and a mini-review.

INTRODUCTION: We report 3 cases of dapsone hypersensitivity syndrome due to anti-malarial chemoprophylactic treatment with maloprim, in military servicemen, presenting like a viral exanthem. CLINICAL PICTURE: Three male military recruits presented with fever and rash, 6 to 8 weeks after commencing on weekly doses of maloprim. TREATMENT: A course of topical and systemic corticosteroids and oral antihistamines were started. OUTCOME: All cases showed gradual resolution of fever, rash and eventual normalisation of liver function test. CONCLUSION: A high index of suspicion was required before this uncommon syndrome can be recognised. Early institution of corticosteroid therapy and discontinuation of maloprim are the mainstays of treatment.

Leiomyomatosis-like lymphangioleiomyomatosis of the colon in a female with tuberous sclerosis.

Smooth muscle lesions of the large bowel, excluding the rectum, are generally rare, and diffuse smooth muscle lesions, termed leiomyomatosis, are even rarer. In this report, we document, for the first time, leiomyomatosis-like lymphangioleiomyomatosis (LAM) of the ascending, transverse, and descending colon in association with bilateral renal angiomyolipoma (AML) in a 30-year-old Chinese female with tuberous sclerosis complex (TSC). She presented with protracted constipation for which a colectomy was performed. Histology disclosed multiple confluent nodular CD34 and CD117 negative smooth muscle proliferation within the large bowel wall, whereas the renal biopsy revealed typical features of AML. Interestingly, the epithelioid smooth muscle cells of both the colonic and renal lesions were HMB45 positive, suggesting that leiomyomatosis-like LAM of the colon, pulmonary LAM and AML are closely related entities. The patient remained free of complications for the last five years after surgery. Leiomyomatosis-like LAM of the large bowel probably represents another manifestation of the tendency of TSC to be associated with proliferative lesions.

Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.

An unusual orbital bone lesion.

A case of Langerhans cell histiocytosis involving the left orbital ridge in an 11-year-old girl is reported. The clinical presentation, radiologic findings and histopathological features as well as diagnostic criteria for Langerhans cell histiocytosis are reviewed.

Cytochrome P4501A2 (CYP1A2) activity and lung cancer risk: a preliminary study among Chinese women in Singapore.

There is increasing evidence for the role of heterocyclic and other arylamines in carcinogenesis, including lung carcinogenesis. Chinese women have a high rate of lung cancer despite a low smoking prevalence, and studies in this population may provide useful information on risk factors other than smoking. Hepatic CYP1A2 and NAT2 are involved in the metabolism of carcinogenic arylamines, and NAT2 also catalyzes the detoxification pathway for these compounds. In this study, we examined the effect of CYP1A2 activity using a urinary caffeine metabolic ratio assay for 54 Chinese women with newly diagnosed lung cancer (including 28 adenocarcinomas) and 174 hospital controls. Among them, NAT2 genotype was available for 47 cases and 98 controls. There was no effect of CYP1A2 activity on overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and cruciferous vegetable intake]. For adenocarcinomas, the OR was 1.5, 95% CI 0.6-3.4. After further adjustment for NAT2 acetylator genotype, the OR for adenocarcinoma was 1.8 (95% CI 0.7-4.8). When the combined NAT2/CYP1A2 status was examined, women with slow NAT2 and rapid CYP1A2 activity were at highest risk (adjusted OR 6.9, 95% CI 1.3-37.6) relative to women with rapid NAT2 and slow CYP1A2 activity, for lung adenocarcinoma. While larger studies are needed to confirm or refute these results, they are consistent with a role for heterocyclic arylamines in lung carcinogenesis in this primarily non-smoking population.

Recurrent nasopharyngeal carcinoma presenting as diffuse dermal lymphatic infiltration in the neck: three case reports.

BACKGROUND: Any malignancy has the propensity to metastasize to skin. The frequency of skin metastases vary in different tumors and occur in about 0.7% to 10% of all patients diagnosed with cancer. It is rare in nasopharyngeal carcinoma. METHOD: Three cases of relapsed nasopharyngeal carcinoma with diffuse dermal involvement were described. Their clinical presentation, results of investigations, and response to treatment were reviewed. Literature review of similar forms of presentation was done by means of a MEDLINE search. RESULTS: At the time of dermal relapse, all three patients had a uniform clinical picture of facial, periorbital, and lip swelling associated with stridor and dysphagia. Histologic findings showed dermal infiltrates of malignant cells, and CT scan showed diffuse infiltration of the subcutaneous tissue. Despite chemotherapy, the clinical course was relentless. CONCLUSION: This report describes a presentation of disease that is underdiagnosed and heightens awareness of oncologists to this form of recurrence in nasopharyngeal carcinoma.

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.

Hard metal lung disease--the first case in Singapore.

INTRODUCTION: We report the first case of hard metal lung disease in Singapore and the occupational investigative work and control measures that were undertaken. CLINICAL PICTURE: A 38-year-old machinist in the tool manufacturing industry presented with exertional dyspnoea and cough. Chest X-ray revealed bilateral reticulonodular infiltrates with honeycombing. High resolution computed tomography scan of the thorax confirmed the presence of interstitial fibrosis. Open biopsy of the lung showed features of pneumoconiosis. Particle induced X-ray emission (PIXE) analysis, a relatively new elemental analysis technique, performed on the lung biopsy specimen confirmed the presence of tungsten and titanium; and he was diagnosed to have hard metal lung disease. Microbiologic, serologic and histologic investigations excluded an infective cause. Serial pulmonary function tests on follow-up showed no progression. He presented with haemoptysis 10 months later and was diagnosed to have tuberculosis on the basis of positive sputum and bronchoalveolar lavage cultures for Mycobacterium tuberculosis complex. TREATMENT: Preventive measures and permanent transfer to non-cobalt work were instituted. OUTCOME: The interstitial fibrosis appears to have stabilised. CONCLUSION: The diagnosis of hard metal lung disease must be considered in a worker exposed to cobalt presenting with interstitial fibrosis.

Impact of inadequate fine-needle aspiration cytology on outcome of patients with palpable breast lesions.

BACKGROUND: The purpose of the present study was to assess the impact of inadequate fine-needle aspiration cytology (FNAC) breast specimens on the outcome of patients with a palpable breast lesion. METHODS: A retrospective review was carried out of inadequate FNAC specimens from the Department of General Surgery, Singapore General Hospital in 1997. RESULTS: One hundred and thirty-eight (16.6%) of 831 FNAC specimens were reported inadequate, and these form the study group. Outcome analysis was divided into benign on excision biopsy (n = 38; 29.4%); benign on repeat FNAC or trucut biopsy (n = 6; 4.7%); benign on follow up (n = 46; 35.7%); malignant on histology (n = 11; 8.5%); and lost to follow up (n = 28; 21.7%). The 11 cases with breast cancer were further analysed. The mean time to treatment was 88.3 days for three patients whose tumours were not clinically suspicious of malignancy versus 20 days for six patients who were diagnosed with cancer clinically from the onset. One patient with cancer refused treatment and one absconded from treatment only to return 7 months later. CONCLUSION: Breast cancer was present in 8.5% of the inadequate FNAC specimens. When clinical suspicion of malignancy is high, an excision biopsy is advised in patients with inadequate FNAC specimens. If properly managed with triple tests and good clinical judgement, the inadequate FNAC specimens do not delay treatment in patients with breast cancer.

The diagnostic yield of pleural fluid cytology in malignant pleural effusions.

BACKGROUND: The development of a pleural effusion in a patient with a known malignancy often raises the possibility that the effusion is due to malignant involvement of the pleura. Accurate diagnosis of the cause of the pleural effusion in such a patient is essential as the treatment and prognosis may vary. Currently, thoracentesis and cytologic analysis of pleural fluid cytology is usually the initial diagnostic step. AIM: To assess the diagnostic yield of pleural fluid cytologic examination in patients with suspected malignant pleural effusions seen at our centre. METHODS: Retrospective review of the results of pleural fluid cytologic examination performed on 103 patients who presented with suspected malignant pleural effusions. RESULTS: The underlying malignancies in these patients were as follows: bronchogenic carcinoma (51.5%), breast carcinoma (29.1%), hepatocellular carcinoma (1.9%), carcinoma of the stomach (1.9%), malignant mesothelioma, nasopharyngeal carcinoma, renal cell carcinoma, carcinoma of the oesophagus, lymphoma, carcinoma of the colon (1% each), unknown (9.7%). Initial pleural fluid cytology was positive for malignancy in 48.5% of patients. The yield of this diagnostic procedure was improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. There was no statistically significant difference in the clinical features and pleural fluid characteristics of patients with malignant pleural effusions and those in whom the pleural effusions were paramalignant. CONCLUSION: Pleural fluid cytologic examination is a useful initial step in the diagnostic work-up of patients with suspected malignant pleural effusions. The diagnostic yield of such examination is improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy. Clinical presentation and pleural fluid characteristics were inadequate in differentiating between malignant and paramalignant effusions.

Technical aspect of ThinPrep.

AIM OF STUDY: To analyze the common technical problems encountered in ThinPrep preparations. METHOD: A prospective and retrospective study of eight hundred and fifty (n = 850) conventional cervical smears with its corresponding paired ThinPrep specimens from July 1998 to December 1998. RESULTS: 139 ThinPreps were found to be technically suboptimal. Of these, 81 showed "patchy cells lost"; 18 showed "thick preparations"; 24 demonstrated "halo effect'" where the cellular material collected at the periphery of the cell circle, and 16 had "obscuring blood and amorphous debris", rendering the preparations "satisfactory for evaluation but limited" by the presence of the above artifacts. CONCLUSION: Despite its many advantages in providing standardization of specimen preparation, superb cellular presentation, reduction in the number of unsatisfactory reports and increased lesion detection rate, ThinPrep has its own limitations in terms of technical problems, ease of operation and cost effectiveness.

NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore.

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

A comparison of trucut biopsy with fine needle aspiration cytology in the diagnosis of breast cancer.

INTRODUCTION: Carcinoma of the breast is common in Singapore and many patients may present with just a suspicious breast lump. AIM: To determine the accuracy of fine needle aspiration cytology (FNAC) and trucut biopsy in the diagnosis of suspicious breast lumps in an outpatient setting. METHODS: A total of 39 women, from May 1995 to November 1995, who had a suspicious breast lump were subjected to concurrent FNAC and trucut biopsy. RESULTS: The accuracy of FNAC is 90% whereas trucut biopsy is 67%, the difference being statistically significant with a p < 0.02. CONCLUSION: FNAC is recommended for the diagnosis of suspicious breast lumps.

Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case report.

An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented as a pituitary tumour in a young adult Chinese female, who subsequently died after having undergone trans-sphenoidal resection. Metastatic cancers of the pituitary are uncommon even in necropsy series and rarely give rise to clinical symptoms. This case draws attention to the fact that, although uncommon, pituitary metastases have been noted with increasing frequency and their distinction from primary pituitary tumours is often difficult. A metastatic pituitary tumour may be the initial presentation of an unknown primary malignancy, wherein the metastatic deposits may also be limited to the pituitary gland. Clinicians and pathologists alike should consider a metastatic lesion in the differential diagnosis of a non-functioning pituitary tumour.

Desmoid tumor (fibromatosis) of the breast. A clinician's dilemma--a case report and review.

Desmoid tumor of the breast is a clinician's dilemma as it is difficult to differentiate it from carcinoma clinically, mammographically, and cytologically. Histologically, it must be distinguished from fibrosarcoma. Current management favors wide excision with clear margins. Recurrence is relatively common and usually occurs within 3 years of excision. Adjuvant hormonal therapy does not reduce local recurrence rates; evidence indicates that postoperative radiotherapy can improve the 10-year recurrence-free survival rate.