The Epstein-Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's disease. Western cases of Hodgkin's disease have shown the presence of EBV in Hodgkin and Reed-Sternberg cells in approximately 50%. We studied a total of 100 consecutive cases of Hodgkin's disease from Malaysia, with the aim to elucidate its association with EBV in a multi-ethnic Asian population. Of 34 patients (34%) less than 15 years of age (childhood), 25 had classical Hodgkin's disease (eight nodular sclerosis, 16 mixed cellularity, one lymphocyte depleted) and nine had lymphocyte predominance Hodgkin's disease. Of the 66 from patients aged 15 years and above, 33 had nodular sclerosis, 24 mixed cellularity, two lymphocyte depleted, one unclassifiable and six lymphocyte predominance Hodgkin's disease. The ethnic distribution of classical Hodgkin's disease was: Malay 23, Chinese 32 and Indian 30 (Malay:Chinese:Indian = 1:1.4:1.3), and the ethnic distribution in the 15 cases of lymphocyte predominance Hodgkin's disease was: Malay four, Chinese 10 and Indian one. Taking into account the ethnic distribution of the general population and of hospital admissions, there appears to be a significant predilection of classical Hodgkin's disease cases in ethnic Indian compared to non-Indian patients (chi-squared test, 0.025 > P > 0.01). Eighty-one cases were tested for the presence of EBV by in situ hybridization for EBV encoded RNA, and 57 cases by immunostaining for EBV latent membrane protein 1. In the younger age group, all except one of the 15 cases (nine mixed cellularity, six nodular sclerosis) showed the presence of EBV (93%). In the older age group, EBV was detected (52%) in the following proportion: 6/27 nodular sclerosis, 19/22 mixed cellularity, 1/2 lymphocyte depleted, 1/1 unclassifiable. None of the 14 cases of lymphocyte predominance Hodgkin's disease showed the presence of EBV in the Hodgkin and Reed-Sternberg cells. The findings suggest a strong association of EBV with Hodgkin's disease in Malaysians (41/67, 61%), in particular childhood cases (93%). In adults, the association with EBV is significantly higher in the mixed cellularity subtype (86%) compared with the nodular sclerosis subtype (22%).
One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.
A 39-year-old female presented with a mobile 1.5 cm nodule in the right breast. Fine needle aspiration cytology smears stained with May Grunwald Giemsa were highly cellular with a monotonous population of dissociated and clustered tumour cells that showed a bland cytological appearance with cytoplasmic vacuolation and occasional signet ring forms. Intracellular and extracellular mucus was present. Histological study of the excised breast mass showed a secretory carcinoma. This is a rare breast neoplasm in which cytological features are characteristic enough to permit a specific diagnosis on needle aspirates.
A retrospective study was conducted to investigate whether there was a correlation between the histological pattern of renal amyloidosis, the chemical type of amyloid protein involved and the clinical presentation. Eighteen consecutive cases of systemic amyloidosis that had renal biopsies processed and examined histopathologically at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur were reviewed. The age range of patients was 25 to 64 yrs (mean, 46 yrs). The male:female ratio was 2.6:1. Three patients were Malay, 9 Chinese, 3 Indian, 1 Indonesian, 1 Iban, and 1 Bisaya. According to the predominant site of amyloid deposition, 14 cases showed a glomerular pattern and 4 a vascular pattern. 8 cases were designated as 2 anti-human amyloid-A (AA) amyloidosis on the basis of permanganate-sensitivity and immunoreactivity of deposits with anti-human AA protein antibody. Ten cases contained deposits that were permanganate-resistant and nonimmunoreactive for AA protein and were designated as AL in type. The histomorphologic pattern of renal amyloidosis did not provide a reliable means of differentiating AA from AL amyloidosis. The glomerular pattern tended to present with renal manifestations such as nephrotic syndrome and chronic renal failure, whereas the vascular pattern tended to present with nonrenal manifestations such as diarrhoea. These findings may have a bearing on the pathophysiology of amyloidosis and provide clues to appropriate management.
Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.
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.
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).
Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
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 review of routine histopathological samples and autopsies examined at the Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of the lung. Two were localized depositions limited to the lung while in the remainder, lung involvement was part of the picture of systemic amyloidosis. Both cases of localized amyloidosis presented with symptomatic lung/bronchial masses and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated with heavy plasma cell and lymphocytic infiltration and the presence of multinucleated giant cells. In both cases, the amyloid deposits were immunopositive for lambda light chains and negative for kappa chains and AA protein. One was a known systemic lupus erythematosus patient with polyclonal hypergammaglobulinaemia. The other patient was found to have plasma cell dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis was not obvious clinically or macroscopically but was histologically evident in 75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of arterioles and small vessels, and along the alveolar septa. It was less frequently detected in the pleura, along the basement membrane of the bronchial epithelium and around bronchial glands. In one case of systemic AL amyloidosis associated with multiple myeloma, an "amyloidoma" occurred in the subpleural region reminiscent of localized amyloidosis. These cases pose questions on (1) whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL amyloidosis and (2) the differing pattern of tissue deposition of different chemical types of amyloid fibrils, with the suggestion that light chain amyloid has a greater tendency to nodular deposition than AA amyloid.
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.
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.
Medico-legal problems experienced by histopathologists differ from those of other clinicians as they are rarely in direct contact with patients. Nevertheless, the pathologist owes a duty of care to the patient and is liable for medical negligence. In the absence of local guidelines, it is prudent to follow guidelines published by learned Colleges elsewhere. This is also true when delegating duties to non-pathologists, technical and other support staff. Errors in diagnosis and documentation pose the most common problems in histopathology. In this, liability also depends on many factors including the provision of adequate clinical information by clinicians and competence of laboratory staff. Clinicopathological discussions, participation in quality assurance programmes and adherence to standard operating procedures are important audit activities to minimize and detect errors as well as prevent grievous outcome to patients. Issues also arise over the retention of specimens and reports. In general, wet, formalin-fixed tissues should be kept until histopathological assessment is finalized and preferably after clinicopathological sessions, and even longer if there is potential litigation. Reports should be archival. Paraffin blocks should be kept for at least the lifetime of the patient, and histology slides for at least 10 years, to facilitate review and reassessment. Despite adverse publicity in the foreign press over the use of human organs and tissues for research and education, it is accepted that processed tissues can be used for research and educational purposes provided the patient's identity is kept confidential. Nevertheless, it would be prudent to revise consent forms for surgery and autopsies to include the possibility that tissues removed can be stored or used for research and education. Good medical practice in pathology encourages a willingness to consult colleagues when in doubt, but advises that the treating clinician be informed if histopathological material is referred away for a second opinion. The Telemedicine Act of Malaysia (1997) requires practitioners outside Malaysia providing diagnosis through telepathology to hold a certificate to practice telemedicine issued by the Malaysian Medical Council. It is likely that the medico-legal scene in histopathology will change in the coming years with the advent of other new ancillary investigative techniques.
This investigation was carried out to gain insight into the prevalence of pS2 expression in invasive ductal breast carcinoma in the Malaysian population and its correlation with oestrogen receptor (ER) protein expression and tumour aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated with mastectomy and axillary lymph node clearance were investigated, using the standard avidin-biotin complex immunoperoxidase method with microwave antigen retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and human ER. This was correlated against histological grade (modified Bloom and Richardson) and the presence of axillary lymph node metastasis of these carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3 tumours. A total of 45 (64%) showed histological evidence of axillary lymph node metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There was a statistically significant correlation between pS2 and ER expressions (chi2-test with Yates correction: P<0.005). There was no correlation between pS2 expression and histological grade (P>0.1) and the presence of lymph node metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of endocrine responsiveness in invasive breast cancer and that it does not influence breast cancer biology in terms of potential for metastatic spread.
Infantile myofibromatosis (IMF) is a rare tumour with a wide spectrum of disease activity ranging from a solitary cutaneous nodule through to a multicentric form with widespread visceral involvement. It is characterised by its unique ability to spontaneously regress and has a typical histological appearance of actin-positive fibroblasts arranged in whorls or fascicles and vessels in a pericytomatous pattern. A male infant with multiple lesions involving the subcutaneous tissue and bone from birth is described and followed-up for two years. Treatment of IMF is dependent on the location of the tumour/s with surgery or chemotherapy reserved for rapidly progressive or symptomatic disease. However, due to the low rate of recurrence and the possibility of spontaneous tumoral regression, therapeutic abstention, as practised in our patient, is justified.