Kimura's disease: a diagnostic and therapeutic challenge.

INTRODUCTION: Kimura's disease (KD) is a rare, benign, chronic inflammatory disease with unknown aetiology. Its manifestation is protean. KD has a predilection for the head and neck area, and typically presents as tumour-like lesions that could be easily misdiagnosed. We review our experience with four recent cases. METHODS: Over a four-year period, all patients admitted to Singapore General Hospital with KD of the head and neck region were retrospectively reviewed. Biodata, presenting symptoms and clinical parameters, especially serum eosinophil levels, preoperative investigations, type of surgical procedures and outcome were documented. RESULTS: Four patients presented with KD of the head and neck and displayed varied manifestations of the disease. All the patients had raised serum eosinophil levels. None of them had renal involvement. Preoperative computed tomography were performed in two of the patients and showed features suggestive of KD. Fine-needle aspiration cytology that was performed in two patients was not useful in the diagnosis. All the patients underwent surgical excision of the lesions. Only one patient had multiple recurrence, both at the original and remote sites in the head and neck. CONCLUSION: The clinical presentation and behaviour of KD is very variable. Preoperative imaging is useful in the diagnosis of the disease but the final diagnosis is histological. Surgical excision is the current treatment of choice but recurrence is common. A high index of suspicion and awareness is vital in the early diagnosis and management of KD.

A clinical review of granulosa cell tumours of the ovary cases in KKH.

INTRODUCTION: Granulosa cell tumour (GCT) represents the largest group of sex-cord stromal tumours and comprises 1.5-3% of ovarian malignancy. The aim is to determine the incidence of the disease, study the profile of local patients, and assess the use of imaging studies in the diagnosis of the tumour. MATERIAL AND METHODS: Clinical records of 19 patients diagnosed with GCT between October 1988 and July 1997 in Kandang Kerbau Hospital (KKH) were reviewed. RESULTS: GCT accounts for 3.5% of ovarian malignancy (54 out of 1552) in Singapore, of which 94.7% are adult GCT. In our study, patients are mainly peri/postmenopausal women (63.2%) in their 50s who experience post-menopausal bleeding. There is a high incidence of association with endometrial hyperplasia (40%). Ultrasound scans are able to predict the size and involvement of the tumour rather accurately. In our study sample, 13 patients (68.4%) presented with Stage 1 of the disease, none with Stage 2, 1 with Stage 3 (5.3%) and none with Stage 4. The other 5 patients (26.3%) were unstaged. Only one patient required adjuvant chemotherapy. CONCLUSION: The local data with regards to GCT is congruent with those found in foreign literature. However, in our study, there were no patients with recurrence whereas GCTs are known to be late recurring in up to 20% of patients 10-20 years after diagnosis. This is probably attributed to the relatively short period of follow-up in this study. Thus, despite the fact that there is no evidence of recurrence of disease in our current study, we still recommend a vigilant follow-up protocol on all patients as literature has proven that with early detection of recurrences, it is possible to achieve complete cure.

Primary ovarian pregnancy: current diagnosis and management.

We reviewed five cases of ovarian pregnancy that were diagnosed at the Kandang Kerbau Hospital Histopathology Laboratory over three years. The clinical presentation, diagnosis and management of these patients are discussed in detail. This condition usually occurs in parous fertile women as evidenced by three of the five patients studied. It is probably an accidental event with no predisposing features as compared to the tubal pregnancy patient. The diagnosis has been aided by the recent advances in human chorionic gonadotrophin determination and ultrasound. Ultrasound, especially transvaginal ultrasound scanning has proven to be an invaluable tool in the diagnosis of this condition. Fertility after conservative surgical procedures does not appear to be affected and ovarian wedge resection or ovarian cystectomy is the treatment of choice.

A case of localised ureteric amyloidosis.

We describe a case of localised amyloidosis of the distal ureter in a 66-year-old lady who presented with intermittent haematuria. Ureteric transitional cell carcinoma was strongly suspected from the clinical and radiological features, and subsequent nephroureterectomy was performed. Histology revealed nodular eosinophilic deposits in the ureteric wall, with the staining characteristics of amyloid. The literature is reviewed, and conservative surgery is advocated, based on a greater awareness together with improved intraoperative diagnosis of this rare lesion.

Primary unruptured ovarian pregnancy--a case report.

A rare case of an unruptured ovarian ectopic pregnancy is reported. This patient had a dilatation and curettage for an incomplete abortion and no products of conception were revealed in the histology specimen. A repeat ultrasound scan detected an ectopic pregnancy. Laparotomy confirmed the diagnosis of an unruptured ovarian pregnancy. The problems with the diagnosis and the management of this case are discussed.

Primary extrauterine endometrial stromal neoplasms: a clinicopathologic study of 20 cases and a review of the literature.

We present the results of a clinicopathologic study of 20 patients with primary extrauterine endometrial stromal sarcoma (ESS). The sites of the primary neoplasm and the number of patients with sufficient follow-up for survival analysis are as follows: ovary (three of four), fallopian tube (one of one), pelvic cavity (six of eight), abdominal cavity (five of six), and retroperitoneum (one of one). Evaluation of all patients included the mitotic index (MI) and cytologic atypia. Thirteen of the sixteen patients eligible for survival analysis had tumors with an MI < 10 and would be classified as low-grade stromal sarcomas in the Norris and Taylor scheme. Eight (62%) of the 13 had one or more relapses; of these, three died of disease at 35, 108, and 120 months, respectively, and another patient was alive with disease at 96 months. The other four patients who were treated after a relapse showed no evidence of disease after relapse at 36, 57, 63, and 146 months, respectively. Two of the 13 patients had tumor considered unresectable at the time of diagnosis; both died of disease at 5 and 10 months, respectively. Neither MI nor cytologic atypia were predictive of tumor recurrence or death from tumor. We also extracted clinical and morphologic data from all previous reports of primary extrauterine ESS, combined them with our 20 patients, and then compared the combined group with 17 cases of primary high-stage uterine ESS we presented in an earlier report. Not surprisingly, the behavior of the primary extrauterine ESS was more reminiscent of high-stage primary uterine ESS than low-stage primary uterine ESS.

Benign teratoma of the fallopian tube: a case report.

A benign teratoma of the fallopian tube in a 33-year-old woman with primary subfertility is reported. This is the first case reported in Singapore. The features of benign teratoma of the fallopian tube is discussed.

Fine needle aspiration of 123 head and neck masses--an initial experience.

Fine needle aspiration (FNA) is a relatively new technique in the investigation of head and neck masses in Singapore. We present our initial experience with 123 neck masses; 82 were lymph nodes, 33 were salivary gland masses and eight were others. The inadequacy rate (percentage of hypocellular yields) was 12.2% with a cytology: histology accuracy rate of 82.6%. The aspiration trolley set-up and improvements in tissue handling reduced the number of inadequate smears. A study of nasopharyngeal carcinoma (NPC) with neck recurrence showed the difficulty encountered with FNA in irradiated necks. In "occult" (clinically normal nasopharynx) NPC with a neck mass as the first presentation, FNA guided us to re-search the nasopharynx.

Embryonal carcinoma arising in Turner's syndrome.

Risk of malignant transformation in a dysgenetic gonad is high. This is a report of a 23 year-old female who presented with symptoms and signs of ovarian neoplasm which was histologically confirmed as embryonal carcinoma. She had features of Turner's syndrome and was found to have XO chromosomal constitution. Embryonal carcinoma arising in a dysgenetic gonad is uncommon. It is even rarer when it arises in a patient with pure 45 XO. The following is a case report which highlights the role of chemotherapy and surgery in the management. It includes a literature review on the clinical features, genetic variants and malignant transformation in dysgenetic gonad. The role of prophylactic removal of dysgenetic gonad is discussed.

Patterns and implications of subclinical vulval human papillomavirus infection: the impact of PCR analysis.

This study was performed to elucidate the presence of human papillomavirus (HPV) infection of the vulva by colposcopy, histology and the polymerase chain reaction (PCR). Colposcopy defined 5 patterns of vulval epithelial lesions inconspicuous to the naked eye. Of these 75 subclinical vulval lesions, HPV infection was diagnosed by histology in 20.0% of minor epithelial changes with faint acetowhitening, 52.2% of conspicuous acetowhite lesions, 63.0% of acetowhite areas with satellite lesions, 84.6% of villous lesions, and 85.7% of villous lesions with surrounding acetowhitening. The corresponding HPV DNA positivity rates by PCR were 60.0%, 73.9%, 70.4%, 84.6% and 100% respectively. The oncogenic HPV type 16 was detected by PCR in 37.3% of the samples. These results provide firm evidence for the prevalent existence of subclinical HPV lesions of the vulva. Some of these infections may not produce significant morphologic changes detectable by colposcopy or histology. Subclinical vulval lesions are common and may constitute a reservoir for repeated cervical HPV infections, as well as a source of contamination of cervical samples for HPV DNA detection by sensitive molecular techniques.

The diagnostic value and patient acceptability of outpatient endometrial sampling with Gynoscann.

Endometrial sampling with Gynoscann was performed in the outpatient department in 70 women with abnormal vaginal bleeding prior to dilatation and curettage (D&C). Successful endometrial sampling was achieved in 62 (89%) patients; Of the samples obtained 44 (71.0%) were adequate for cytological assessment and 46 (74.2%) for histological assessment, compared to 80% of D&C samples being adequate for histological examination. In those patients in whom outpatient endometrial sampling was adequate, both the cytological and histological diagnosis agreed with the D&C. The outpatient endometrial sampling was well tolerated by the patients since the majority (89%) experienced either no or little pain. Vaginal bleeding following the procedure was minimal in all except 1 patient. Endometrial sampling with Gynoscann may be useful for endometrial assessment prior to commencement of hormonal therapy and hysterectomy. It is a potentially useful screening test for early detection of endometrial cancer in patients at risk.

Extraskeletal osteogenic sarcoma--a case report.

A rare case of extraskeletal osteogenic sarcoma of the right groin in a 50 year old Chinese lady is being presented. A wide excision of the tumour was done. The differential diagnosis are discussed. This is an extremely rare tumour and is just as malignant and aggressive, if not more so than its counterpart in the bone.

Diagnostic sensitivity of polymerase chain reaction and Southern blot hybridization for the detection of human papillomavirus DNA in biopsy specimens from cervical lesions.

Human papillomaviruses (HPVs) are associated with benign and malignant neoplasms of the cervix. One of the criteria for their etiologic role requires an assessment of whether virtually all or only a small fraction of lesions contain viral genomes. DNA preparations from colposcopically directed punch biopsies of cervical lesions were analyzed by Southern blot hybridization and the polymerase chain reaction (PCR) for the presence of HPV DNA. The biopsy specimens represented different pathologic entities (koilocytosis, condyloma, cervical intraepithelial neoplasia, and invasive carcinoma). In Southern blot hybridization with radioactive probes for HPV 11, 16, 18, 31, and 33, HPV DNA was detected in 74% of the biopsy specimens (42 of 57 cases), with the predominant types being HPV 16 and HPV 18. In contrast, after PCR amplification with primers yielding fragments of characteristic size for HPV 11, 16, and 18, the analysis of the same 57 biopsy specimens revealed that all samples were positive for at least one HPV type. To exclude false-positive PCR results, controls without HPV DNA were interspersed at regular intervals, and results were evaluated only if these controls remained HPV negative. To exclude false-negative results due to failure of the reaction, a target sequence within the c-Ha-ras-1 gene was used as an internal control. All HPV typing results obtained by Southern blot hybridization were in agreement with HPV typing by PCR. The higher number of positive samples in the latter analysis stems from the increased sensitivity of PCR, which was which was effective in identifying as few as 10-100 HPV DNA molecules; in contrast, the sensitivity of Southern blot hybridization was 1 pg, or approximately 10(5) molecules of HPV DNA. The authors conclude that, with sufficiently sensitive diagnostic methods, HPV DNA can be detected in most, if not all, neoplastic cervical lesions.

Subclinical human papillomavirus infection of the male lower genital tract: colposcopy, histology and DNA analysis.

In 25 partners of women with genital human papillomavirus (HPV) infection or cervical intraepithelial neoplasia, colposcopic examination revealed the existence of subclinical HPV infection of the male lower genital tract in 22 cases. It manifested either as short papillae tipped with acetowhite changes, or flat acetowhite lesions on the foreskin, glans, periurethral region, scrotum, perineum and/or perianal region. Multiple lesions involving several anogenital areas were common. Some of these abnormalities were small and inconspicuous. Of these 22 cases, 17 had histological evidence of HPV infection. Although Southern blot hybridization detected HPV DNA in only one case, polymerase chain reaction (PCR) analysis revealed HPV DNA in 20 cases. There were 10 cases of HPV 16. Subclinical HPV disease is best identified by colposcopy and confirmed by PCR. In treating HPV disease, colposcopic recognition of subclinical HPV disease forms an essential part of the management plan.

Genital human papillomavirus infection among women from major ethnic groups in Singapore.

The close epidemiological relationships between specific genital human papillomavirus (HPV) types and neoplasia of the cervix uteri have been extensively documented worldwide, including Singapore. Cervical cancer incidence rates in Singapore show variations between the major ethnic groups. To ascertain the corresponding HPV infection rates among the various races in Singapore, we analysed the cervical smears of 225 women by filter in situ DNA hybridization, and compared the data with a previous similar study. Fourteen (6.2%) individuals were HPV-positive, with HPV 16 and HPV 31 being the commonest types. No significant difference between HPV positivity rates in Chinese (5.0%) and in Malays (6.7%) was found, even though Chinese have a higher cervical cancer incidence than Malays. Furthermore, the cervical HPV carriage rate among women with normal cytology was 5.9%. In the light of reports of high genital HPV prevalence rates detected by DNA amplification, these data support the notion that HPV infection is commonly latent and requires the cooperation of other factors for cervical carcinogenesis.

Is genital human papillomavirus infection always sexually transmitted?

The occurrence of genital human papillomavirus (HPV) infection was studied prospectively by colposcopy and histology in 43 virginal and 162 sexually active women attending a colposcopy clinic. The study also included 111 husbands of the latter group. By colposcopic criteria, the prevalence of HPV infection was 51.1% in the virginal and 69.1% in the sexually active women. The prevalence was 77.1% among men whose wives had HPV infection compared to 13.3% among men whose wives did not have the infection (p less than 0.01). There was a strong association in genital HPV infection between husbands and wives as expected from a sexually transmissible disease. However, the high prevalence of the infection among the virginal women indicated that transmission of HPV by nonsexual modes was common. Genital HPV infection is ubiquitous and in women is not exclusively a venereal disease.

PIP: Human papillomavirus (HPV) infection of the genital tract was assessed in 205 women and 111 spouses by clinical exam, colposcopy and histological examination of punch biopsies. All were patients referred to the colposcopy clinic: 43 were virgins and 162 women were sexually experienced. Among the virgins 51.2% had colposcopic evidence of HPV infection, 9 had microwarts and 1 had condylomata acuminata. 86.4% of these were confirmed histologically. Among the sexually active women 69.1% had colposcopic evidence of HPV, 20.5% had microwarts and 4.5% had condylomata acuminata. 37 had neoplasia. 85.7% of Hpv cases were confirmed histologically, as were 8.0% of women without evidence of HPV. 77.1% of the 96 husbands whose wives were free of infection had HPV. Since many of the virgins, including 2 daughters of a woman with cervical cancer, had genital warts, HPV is probably transmitted by formites as well as by sexual contact.

Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases.

We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors.

Molecular diagnosis of genital HPV DNA types by polymerase chain reaction and sensitivity-standardized filter in situ hybridization in randomly sampled cohorts of Singapore women.

Infection of the cervix uteri with various types of human papillomaviruses is generally considered a necessary factor in the etiology of cancer of the cervix uteri. In many human populations throughout the world, approximately 90% of cervical carcinomas are found to harbour HPV genomes, as judged by Southern blot hybridization, while only a few percent of the cervical smears of asymptomatic individuals contain viral DNA, as assessed by filter in situ hybridization. To obtain corresponding epidemiological data from Singapore, we analysed two groups of 740 and 130 individuals by filter in situ hybridization, and found 4.1% and 6.9% of them to be HPV positive, with HPV 16 and HPV 31 being the predominant types. In consideration of the limitations of filter in situ hybridization, namely low sensitivity and a tendency to suggest false positives due to contaminants, including blood, we analysed the cervical smears of two further groups of 52 and 50 individuals by the polymerase chain reaction for infection by HPV 16 and HPV 18 respectively. With this test, 61% and 14% of the cervical smears proved to be HPV 16 and HPV 18 DNA positive respectively. We conclude that in Singapore, if not worldwide, the majority of the population the population is infected by genital HPV types, suggesting that factors other than HPV infection are ultimately rate-limiting in cervical carcinogenesis.

Fine needle aspiration cytology in the management of solitary thyroid nodules--a comparison with other diagnostic modalities in cost-effectiveness.

This paper assesses the cost effectiveness of fine needle aspiration cytology (FNAC) as a selection criteria for surgery in solitary thyroid nodules compared to scintigraphy and ultrasonography. 98 patients who had FNAC and histological confirmation, scintigraphy and/or ultrasonography were studied. The use of combined diagnostic discriminants of positive FNAC, clinical suspicion and age above 50 years detected all malignancies and would have resulted in fewer patients being subjected to surgery--51% (FNAC) vs 90% (Scans, U/S). This resulted in cost savings of $800 per patient seen. We conclude therefore that FNAC should be the diagnostic modality of choice and that the routine use of scintigraphy and ultrasonography is not justifiable.

Choriocarcinoma following term pregnancy--a case report.

A patient, with two previous term deliveries, presented with post-partum haemorrhage and spontaneous uterine perforation due to choriocarcinoma, requiring emergency laparotomy. Choriocarcinoma following term pregnancy is a rare form of gestational trophoblastic disease. Such tumour appears to follow a more aggressive course with a more extensive metastatic spread and is less responsive to chemotherapy resulting in a poorer prognosis. Choriocarcinoma presenting as postpartum haemorrhage, and spontaneous tumour perforation with intra-abdominal haemorrhage is even rarer. Early diagnosis is an important factor for the patient's survival. A high index of suspicion is required as the tumour may be overlooked. An aggressive chemotherapeutic regime has improved the overall survival.