Cervical carcinoma, the second most common malignancy in Malaysian females, is aetiologically linked to the human papillomavirus (HPV). A study was conducted at the Department of Pathology, University of Malaya Medical Centre to compare the identification of HPV 6, 11, 16 and 18 in 40 archived formalin-fixed, paraffin-embedded cervical carcinoma by non-isotopic in-situ hybridisation (NISH) and polymerase chain reaction (PCR). HPV L1 ORF consensus PCR was also carried in cases which were negative on HPV type-specific PCR. NISH detected HPV 16 in 13 (32.5%) cases with one case demonstrating a concomitant HPV 18. beta-globin DNA PCR was carried out on the same paraffin block as for NISH in 27 cases and on a different paraffin block in 13, with amplification in 9 of the former and 3 of the latter. Thus only 12 cases were subjected to further HPV PCR. HPV was detected in 10 (83.3%) with HPV 16 in 9 cases and HPV L1 ORF in one. When using the same paraffin block for both methods of HPV detection, NISH detected HPV in 6 and PCR in 7. NISH failed to detect HPV in a case detected by PCR. 2 cases were negative for HPV using both methods. Hence, HPV detection results by NISH and PCR were concordant in 88.9%. Interestingly, NISH detected HPV in 2 cases with non-amplifiable beta-globin DNA. Using an alternative paraffin block for HPV PCR from NISH, HPV DNA was detected in 3 cases, two of which also showed type-specific positivity on NISH. The third case did not reveal type-specific positivity with NISH or PCR but demonstrated HPV DNA on L1 ORF consensus PCR. It thus appears that PCR and NISH can be successfully used to detect HPV in formalin-fixed, paraffin-embedded tissue and in the presence of intact DNA NISH may be as sensitive as PCR.
Sixteen low grade (LSIL), 22 high grade (HSIL) squamous intraepithelial lesions, 28 invasive (13 stage I and 15 stage II-IV) squamous cell carcinoma (SCC) and 15 benign cervices were immunohistochemically studied for involvement of Bcl-2 and Bax proteins in cervical carcinogenesis. 4-microm sections of the cases were immunostained for Bcl-2 (Clone 124: Dako) and Bax (Dako) and staining intensity was rated as 1 (light), 2 (moderate) and 3 (strong) and percentage cellular staining as 0 (negative), 1 (1-25%), 2 (26-50%), 3 (51-75%) and 4 (>75%) with score derived by multiplying staining intensity and percentage positivity. The cut-off value, indicating upregulated expression, was computed as >2 for Bcl-2 and >8 for Bax. Bcl-2 was upregulated (p < 0.05) in HSIL and Bax in SCC when compared with benign cervical squamous epithelium. Bcl-2 expression was confined to the lower third of the epithelium in the benign cervices and LSIL. In HSIL, expression reached the middle and upper thirds. 4 (30.8%) HSIL with upregulated Bcl-2 demonstrated intensification of staining around the basement membrane. SCCs showed "diffuse" (evenly distributed) or "basal" (intensified staining around the periphery of the invading tumour nests) expression of Bcl-2. Of the 5 SCCs with upregulated Bcl-2, 1 of 2 (50%) stage I and 3 (100%) stage II-IV tumours exhibited the "basal" pattern. Benign cervical squamous epithelium, LSIL, HSIL and SCC showed a generally diffuse Bax expression. Thus, Bcl-2 and Bax appeared to be upregulated at different stages of cervical carcinogenesis, Bcl-2 in HSIL and Bax after invasion. Intensification of staining of Bcl-2 at the basement membrane in some HSIL and SCC is interesting and may augur for increased aggressiveness.
Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer with an increasing frequency worldwide. "Nuclear atypia", one of the critical features in histological diagnosis of malignancy and grading of the tumour, is generally ascertained through eyeballing. A study was conducted at the Department of Pathology, University of Malaya Medical Centre to assess whether nuclear area, (surrogate measure for nuclear size) and standard deviation (surrogate measure for nuclear pleomorphism) when objectively measured via computer-linked image analysis differs between (1) benign and malignant liver cells and (2) different grades of HCC. A 4-microm thick H&E stained section of 52 histologically re-confirmed HCC with 36 having benign, non-dysplastic surrounding liver were analysed using the Leica Q550 CW system. 10 consecutive non-overlapping, non-mitotic and non-apoptotic nuclei of HCC and surrounding benign hepatocytes respectively were manually traced at 400x magnification on the computer monitor and the nuclear area for the particular cell computed in arbitrary units by the Leica QWIN software. A total of 360 benign hepatocytic nuclei, 240 low grade HCC and 280 high grade HCC nuclei were traced. The mean nuclear area of the benign hepatocytes (37.3) was significantly smaller (p < 0.05) than that of both low grade (65.2) and high grade HCC (80.0). In addition, the mean nuclear area of high grade HCC was significantly larger (p < 0.05) than the low grade HCC. SD of the nuclear areas was lowest in benign hepatocytes (9.3), intermediate in low grade HCC (25.0) and highest in high grade HCC (25.6). These findings indicate that computer-linked nuclear measurement may be a useful adjunct in differentiating benign from malignant hepatocytes, in particular in small biopsies of well-differentiated tumours, and in predicting survival after surgical resection and transplant.
Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
p53 is the most commonly mutated gene in human cancers. It encodes a 53 kilodalton protein with several evolutionarily conserved domains viz sequence-specific DNA binding, tetramerisation, SH3 molecule binding, C-terminal and N-terminal. Existing in the cell at a very low level and in a relatively inactive form, p53 protein is increased and activated during periods of cellular stress. Unlike other proteins, the increase in protein level and its activation result from modification of the protein rather than genetic transcriptional or translational upregulation. Normally, Mdm2 protein interacts with p53 protein and effectively targets it for ubiquitin proteolysis within an autoregulatory feedback loop. Phosphorylation at the N-terminus reduces p53 interaction with Mdm2 with a resultant increase in p53 protein level. Modification at the C and N termini via phosphorylation or acetylation upregulates binding to specific DNA targets increasing transcription of these downstream genes. The net effect of p53 protein increase and activation lies in arrest of the cell in cycle which allows time for repair of the incurred damage or apoptosis or death of the cell. Failure of these normal protective and adaptive mechanisms caused by mutation of the p53 gene with product of an abnormal protein, loss of p53 protein through interaction with and degradation by HPV E6 protein or overexpressed Mdm2 etc. permits DNA-damaged cells to continue replicating. Left unchecked, this frequently contributes to tumourigenesis. Various methods have been devised to screen for mutations of the p53 gene, still the most common source of failed p53 mechanism. These include immunohistochemical detection of mutated proteins or identification of altered electrophoretic mobility of mutated p53 sequences. Sequencing of the gene nonetheless remains the most accurate method for determination of mutation. Major advances have been made in p53 research but the most meaningful probably lies in the promising results achieved in tumour therapy where introduction of wild type p53 gene has resulted in regression of non-small-cell lung cancer (NSCLC). Many other notable developments in this field include description of p53 homologues, "gain of function" mutants, p53 polymorphisms, angiogenesis-inhibiting properties of wild type p53 protein etc.
A study was conducted at the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur into the histological type (WHO classification), grade (modified Edmondson and Steiner's grading system), mitotic rate, bile production, hyaline globule and Mallory hyaline formation of 52 cases of hepatocellular carcinoma (HCC) diagnosed during a 13-year period between 1st January 1990 to 31st December 2002. In addition, associated cirrhosis, dysplasia (large liver cell dysplasia: LLCD and small liver cell dysplasia: SLCD) and microvascular permeation were also looked for whenever the situation permitted. The patients' ages ranged from 21-years to 85-years (mean = 58.7 years) with a predilection for males and Chinese. Histologically, majority (73.1%) of the tumours demonstrated a trabecular pattern of growth. The bulk (73%) of the tumours were either of grade II or III differentiation. Mitotic activity ranged between 0-100/10 high power fields (hpf) with a mean of 22.2/10 hpf. Bile was noted in 25%, hyaline globules 17.3% and Mallory bodies in one case. Concomitant cirrhosis was present in 73.5%. 73.5% of the cases had associated LLCD. 5 with LLCD also showed SLCD. Microvascular permeation was shown in 76.2% of cases. On comparison with findings from other studies, no major difference seems to exist between the histological characteristics of our HCC cases and that of other populations.
Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.
Since its recognition about 150 years ago, there has been much progress in the understanding of the pathogenesis, prevention, early detection and management of carcinoma of the uterine cervix. Important historical landmarks include the (1) recognition of pre-invasive and pre-clinical lesions, and the devise of various systems for reporting these lesions, (2) improvements in diagnostic techniques particularly colposcopy, (3) advent of therapeutic procedures (electrocoagulation, cryotherapy, laser therapy and loop electrosurgical excision), and (4) recognition of the aetiological relationship between the human papillomavirus and cervical neoplasia. The susceptibility of the cervical transformation zone to malignant change is now well recognised. The WHO classification system remains the one most commonly utilised for histological reporting of cervical cancers. In the recent 1994 update, cervical carcinoma is divided into 3 main categories: squamous cell carcinoma, adenocarcinoma and other epithelial tumours. Squamous cell carcinoma (60-80%) predominates among invasive cervical carcinoma. Recognised variants include verrucous, warty (condylomatous), papillary squamous (transitional) and lymphoepithelioma-like carcinoma. Adenocarcinoma (5-15% of invasive carcinomas) shows an increasing trend in young females. Like its squamous counterpart, preinvasive and microinvasive versions are known. Variants such as mucinous, endometrioid, clear cell, mesonephric, serous, villoglandular and minimal deviation carcinoma are now defined. Adenosquamous carcinoma (5-25%), adenoid-cystic, adenoid-basal, neuroendocrine and undifferentiated carcinomas constitute other epithelial tumours of the cervix. The management of invasive cervical carcinoma remains heavily dependent on its stage. The FIGO staging system remains the most widely used. The 1995 update provides more definite criteria in subdividing stage IA tumours by delimiting stromal invasion of stage IA1 lesions to a maximum depth of 3 mm and a horizontal axis of 7 mm. In Malaysia, an appreciation of the cervical carcinoma problem has to take into consideration the population at risk, its multi-ethnicity, its socio-economic and geographical diversities and the constraints of the health care system. Females form 48.9% of the Malaysian population. 52.9% of them are in the sexually active age group of 15-50 years, indicating a significant population at risk for cervical carcinoma. Cervical carcinoma was the third most common cause of death due to solid tumours among Malaysian females in 1995 following carcinoma of the breast and respiratory tract. East Malaysia is predominantly rural with many communities having limited modern facilities. Such areas imply a lower educational and socio-economic status, raising the worry of a population at higher risk for developing cervical carcinoma. The population: doctor for Malaysia of 2153:1 compares poorly with nearby Singapore. Besides a shortage of doctors, there is also an uneven distribution of doctors, resulting in a ratio in East Malaysia of > 4000:1. Although Malaysia does not have a national cervical cancer-screening programme, many action plans and cancer awareness campaigns have been launched throughout the years, which appear to have made an impact as evidenced by the decreasing mortality rates from cervical carcinoma. Another interesting feature of cervical carcinoma in Malaysia relates to its multiethnic population. In Malaysian Chinese and Malay females, the prevalence of cervical carcinoma ranks second to breast cancer whereas the pattern is reversed in Malaysian Indian females. Studies into its aetiology and pathogenesis are being undertaken and may shed more light on this matter.
A 31-year-old Malay female presented with nephrotic syndrome without renal impairment. Renal biopsy features were in keeping with immunotactoid glomerulopathy (ITG). Non-Congophilic deposits were seen causing thickening of the glomerular capillary basement membrane with segmental accentuation, and widening of the mesangium. Immunofluorescence examination showed moderate amounts of IgG and C3 in the glomerular capillary walls with some in the mesangium. Ultrastructurally, 20-nm thick fibrils with microtubular organisation were present predominantly in the subendothelial region with similar fibrils in the mesangium. Although immunotactoid glomerulopathy and fibrillary glomerulonephritis (FG) have been recognised as entities with extracellular fibrillary material in the kidney, to date much remains to be clarified regarding these 2 conditions. While the renal biopsy findings in this patient are consistent with ITG, her clinical presentation is unlike that of usual ITG in that she is of a much younger age and has no associated haemopoietic disorder. Response to initial treatment of 8 weeks of prednisolone therapy was poor.
Historical cottontail rabbit papillomavirus studies raised early indications of a mammalian DNA oncogenic virus. Today, molecular cloning recognises numerous animal and human papillomaviruses (HPVs) and the development of in vitro transformation assays has escalated oncological research in HPVs. Currently, their detection and typing in tissues is usually by Southern blotting, in-situ hybridization and polymerase chain reaction methods. The complete papillomavirus virion constitutes a protein coat (capsid) surrounding a circular, double-stranded DNA organised into coding and non-coding regions. 8 early (E1-E8) open reading frames (ORFs) and 2 late (L1, L2) ORFs have been identified in the coding region of all papillomaviruses. The early ORFs encode proteins which interact with the host genome to produce new viral DNA while late ORFs are activated only after viral DNA replication and encode for viral capsid proteins. All papillomaviruses are obligatory intranuclear organisms with specific tropism for keratinocytes. Three possible courses of events can follow papillomaviruses entry into cells: (1) viral DNA are maintained as intranuclear, extrachromosomal, circular DNA episomes, which replicates synchronously with the host cell, establishing a latent infection; (2) conversion from latent into productive infection with assembly of complete infective virions; (3) integration of viral DNA into host cellular genome, a phenomenon seen in HPV infections associated with malignant transformation. Human papillomaviruses (HPVs) essentially induce skin and mucosal epithelial lesions. Various skin warts are well known to be HPV-associated (HPVs 1, 2, 3, 7 and 10). Besides HPVs 3 and 10, HPVs 5, 8, 17 and 20 have been recovered from Epidermodysplasia verruciformis lesions. Anogenital condyloma acuminatum, strongly linked with HPVs 6 and 11 are probably sexually transmitted. The same HPVs, demonstrable in recurrent juvenile laryngeal papillomas, are probably transmitted by passage through an infected birth canal. HPVs described in uterine cervical lesions are generally categorized into those associated with high (16, 18), intermediate (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) and low (6, 11, 26, 40, 42, 43, 44, 53, 54, 55, 62, 66) risk of cervical squamous carcinoma. Cervical adenocarcinoma, clear cell carcinoma and small cell neuroendocrine carcinoma have also been linked to HPVs, especially HPV18. Other lesions reported to be HPV-associated are: papillomas, dysplasia and carcinomas in the nasal cavity (HPV 6, 11, 57); squamous papilloma, condyloma acuminatum, and verruca vulgaris of the oral cavity (HPV 6, 11), oral focal epithelial hyperplasia (HPV 13, 32); warty lip lesions (HPV 2): and conjunctival papillomas (HPV 6, 11).
Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus (SLE), with renal involvement and biopsy were immunohistochemically studied for the expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known families belonging to the class II major histocompatibility complex (MHC), using a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for renal trauma and tumours constituted the normal controls. Of the lupus nephritis cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4 Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of 31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative) nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other studies, HLA-DR was expressed in the glomerular capillaries and peritubular capillaries of all and mesangium, tubules (proximal, distal and collecting), veins and arterioles of some normal controls. Interestingly, HLA-DR expression was noted in the arteries of 25% of the normal controls, a finding hitherto not reported. The frequency of lupus nephritis cases expressing HLA-DR in the various anatomical components did not differ significantly from the normal controls except that HLA-DR expression in arteries and arterioles was seen at a significantly increased frequency (p < 0.01) in lupus nephritis. This increased expression did not correlate with the WHO class, activity or chronicity scores. It therefore appears that MHC class II shows increased expression in the arterial system of lupus nephritis kidneys. The significance of this is unclear but could be related to heightened (gamma-interferon activation which may be a de novo phenomenon or result of T cell proliferation and activation in SLE.
Formerly thought to have a constant incidence rate throughout the world, Wilms' tumour (nephroblastoma) has been shown to be less common among Asian children. A retrospective demographic and morphological study of Wilms' tumour histologically diagnosed over a 22-year period at the Department of Pathology, University Hospital, Kuala Lumpur was conducted to assess for inherent demographic and morphological differences between tumours in Malaysian children and those of Western populations. Thirty-seven cases of histologically proven Wilms' tumour qualified for inclusion in this study. 19 patients were Chinese, 13 Malay, 4 Indian and 1 Anglo-asian. 21 were male and 16 were female (M:F ratio = 1.3:1). Their ages ranged from 1 month to 4 years. 70.3% of the patients were below 2 years of age. 36 cases had unilateral and 1 bilateral tumours. Of unilateral tumours, 19 involved the left kidney and 17 the right. Histological assessment, based on criteria of the National Wilms' Tumor Study Group, revealed 20 (52.6%) tumours with a mixed pattern while 8 (21.1%) showed epithelial, 7 (18.4%) blastemal and 3 (7.8%) stromal-predominant patterns. Anaplasia was observed in only 2 tumours (5.3%). There was no obvious difference in age range and sex distribution, laterality of tumours and incidence of anaplasia between this and Western studies. No ethnic predilection was observed. A notably larger percentage of cases were below 2 years of age. Also, a larger proportion of epithelial-predominant and a lower proportion of blastemal-predominant tumours was observed compared with patterns reported from Western populations.
Wilms' tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms' tumour was carried out. Thirty-eight cases were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms' Tumour Study criteria. Archival formalin-fixed, paraffin-embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase-labelled streptavidin biotin kit (Dako). 'Cure' (disease-free survival of 60 months or longer) was documented in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demonstrating immunopositivity in > 75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours.
The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.
Mucins are produced by both benign and malignant gastric epithelium. In general, mucins can be classified into neutral and acidic mucins. The latter are of 2 major types, sulphated (sulphomucins) and carboxylated (sialomucins). A retrospective study was initiated at the Department of Pathology, University Hospital, Kuala Lumpur to histochemically study the mucin profiles of cases of intestinal (IGC) and diffuse (DGC) types of gastric carcinoma in Malaysian patients to determine whether a significant change of mucin type occurs in the event of malignant transformation. 42 IGC and 37 DGC were subjected to alcian blue-periodic acid Schiff and high iron diamine-alcian blue histochemical staining. In addition, 18 cases of gastrectomies performed for benign lesions in the stomach served as normal controls. The number of cases of IGC and DGC which exhibited sulphomucin production was significantly increased (p < 0.001) compared to normal controls. Also, the number of cases of DGC which produced neutral mucin were significantly less (p < 0.05) than the control group. However, there was no significant difference between the number of IGC and DGC cases which demonstrated sialomucin production and normal controls. It appears that while not pathognomonic, a lack of neutral mucin production should alert the pathologist to the possibility of a gastric malignancy, in particular DGC. The likelihood of a malignant lesion would be further supported if there is an increased sulphomucin production.
Eight cases of clear cell sarcoma of kidney were seen in the Department of Pathology, University Hospital, Kuala Lumpur, Malaysia over the 16-year period from 1973 to 1989. Five of the patients were males. Six patients were Malay, one Chinese and one Indian. The patients' ages ranged from 8 months to 3 years. Clear cell sarcoma was the original diagnosis in two patients while six were diagnosed as blastemal-predominant Wilms' tumours at presentation. Metastases developed in five patients. Metastatic sites included the thoracic vertebra, skull, orbit, humerus, radius, ulna, shoulder, lung and liver. The prolonged survival, of 9 years and 9 months, seen in one patient despite omission of Adriamycin (doxorubicin) from the chemotherapeutic protocol is highlighted. We also emphasise the histological factors which are of help in differentiating clear cell sarcoma from Wilms' tumour.
A review of gestational trophoblastic disease diagnosed at the Department of Pathology, University Hospital, Kuala Lumpur from January 1989 to December 1990 using established histological criteria showed 25 complete hydatidiform moles (CHM), 11 partial hydatidiform moles (PHM), 1 invasive mole and 2 choriocarcinoma. The ages of the patients with CHM ranged from 21 to 43 years (mean = 28.5 years) and PHM 20 to 33 years (mean = 27.5 years). The invasive mole occurred in a 42-year-old Malay woman. The two patients with choriocarcinoma were both Chinese and 41 and 46-years old respectively. During the same period, 1,062 non-molar abortions and 13,115 births, inclusive of livebirths and stillbirths were recorded at the University Hospital. The incidence rate of hydatidiform moles was thus estimated to be 1:384 pregnancies. PHM constituted 30% of all molar pregnancies. Hydatidiform moles occurred among the Malays, Chinese and Indians at the rate of 2.43, 2.66 and 3.29 per 1,000 pregnancies respectively. It appears that hydatidiform molar pregnancy has the highest prevalence among the Indians, a finding similar to an earlier Singapore study.
Cytophagic histiocytic panniculitis (CHP) is a recently recognized entity that frequently poses a perplexing diagnostic problem. Although the classical case presents with a relapsing fever, subcutaneous nodules, pancytopenia and liver dysfunction, most patients have in addition a multitude of other manifestations which confuse the clinical picture. Notwithstanding the variable clinical course, the disease frequently terminates in fatal hemorrhage. Diagnosis is based on histological features. A lobular panniculitis with an infiltrate of cytologically benign cytophagocytic histiocytes in skin nodules is the sine qua non of CHP. Hence, a deep skin biopsy which includes subcutaneous fat is mandatory to establish the diagnosis. Published information regarding this newly described entity remains scarce and we report two cases of CHP, one occurring in a 30-year-old Kadazan man and another in a 17-year-old Chinese woman seen at the University Hospital, Kuala Lumpur. The latter case presented with exudative ascites, an unusual feature, possibly due to intra-abdominal panniculitis. In addition, we record the development of cirrhosis in the same patient.
Squamous cell carcinoma-related antigen (SCC-Ag), first described by Kato and Torigoe in 1977, has been cited by various workers as a serological marker for some epithelial neoplasms. The most well-studied is its association with carcinoma of the uterine cervix. In January 1989, we embarked on a prospective, multivariate study at the University Hospital, Kuala Lumpur to assess the usefulness of serologically assaying SCC-Ag (using the Abbott RIA diagnostic kit) in our patients with carcinoma of the uterine cervix. We were also interested to ascertain whether SCC-Ag is a 'general' marker for all histological types of cervical carcinoma or specific for squamous carcinoma. From the time of commencement to June 1990, 35 newly-diagnosed and histologically-proven cases were entered into the study. Of these, 4 were keratinising squamous carcinoma, 18 large cell non-keratinising carcinoma, 3 adenosquamous carcinoma, 7 adenocarcinoma and 3 carcinoma-in-situ. Our preliminary results show that all keratinising squamous carcinoma and 1/3 each of large cell non-keratinising carcinoma, adenosquamous carcinoma and carcinoma-in-situ had positive pre-therapy serum SCC-Ag levels (i.e greater than 2 ng/ml, 2 ng/ml being an arbitrarily selected 'cut-off' value). In contrast, no adenocarcinoma was serologically positive. In addition, keratinising squamous carcinoma had the highest mean pre-therapy serum SCC-Ag level. The results imply that serum SCC-Ag is related to the (1) presence of squamous and not glandular differentiation and (2) degree of squamous differentiation.