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Biomedical subjects

S W McCarthy

Publications and source records attributed to S W McCarthy.

At least 19 recordsLinked to original sources

Myopericytoma: a unifying term for a spectrum of tumours that show overlapping features with myofibroma. A review of 14 cases.

BACKGROUND: Myopericytoma (MPC) is a recently proposed term to describe a group of tumours that originate from perivascular myoid cells and show a range of histological growth patterns. Only a small number of series describing MPC have been reported. MPC is frequently misdiagnosed as a sarcoma. AIMS: To document the clinical and histopathological findings of a series of MPCs, to describe the range of growth patterns and morphological spectrum, and to compare MPC with myofibroma (MF). PATIENTS/METHODS: Fourteen patients with features of MPC and/or MF were identified from the archival files of the department of anatomical pathology, Royal Prince Alfred Hospital, Sydney, Australia. RESULTS: There were six female and eight male patients. The mean and median patient ages were 37 and 35.5 years, respectively. The tumours were located in the skin, subcutis, or superficial soft tissues of the distal extremities (13 patients) or the head and neck region (one patient), and showed a spectrum of morphological appearances. They were divided into two groups based upon the predominant growth pattern corresponding to MPC (seven cases) and MF (seven cases). The feature most suggestive of MPC was the presence of a concentric perivascular arrangement of plump spindle shaped cells. The presence of a zonation/biphasic appearance was most characteristic of MF. CONCLUSIONS: MPC exhibits a spectrum of growth patterns that overlap with MF. Tumours can be designated as MPC or MF depending on the predominant growth pattern.

Adolescent↗

Surgical biopsy with intra-operative frozen section. An accurate and cost-effective method for diagnosis of musculoskeletal sarcomas.

The most appropriate protocol for the biopsy of musculoskeletal tumours is controversial, with some authors advocating CT-guided core biopsy. At our hospital the initial biopsies of most musculoskeletal tumours has been by operative core biopsy with evaluation by frozen section which determines whether diagnostic tissue has been obtained and, if possible, gives the definitive diagnosis. In order to determine the accuracy and cost-effectiveness of this protocol we have undertaken a retrospective audit of biopsies of musculoskeletal tumours performed over a period of two years. A total of 104 patients had biopsies according to this regime. All gave the diagnosis apart from one minor error which did not alter the management of the patient. There was no requirement for re-biopsy. This protocol was more labour-intensive and 38% more costly than CT-guided core biopsy (AU$1804 vs AU$1308). However, the accuracy and avoidance of the anxiety associated with repeat biopsy outweighed these disadvantages.

Biopsy↗

Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma.

BACKGROUND: Several studies suggest that melanoma may be resistant to treatment because of resistance to apoptosis and that this may be the result of activation of the extracellular signal regulated kinase (ERK1/2) pathway. AIMS: To test this hypothesis by examining the expression of ERK1/2 and its activated form in histological sections of melanoma and its relation to known prognostic features of the disease. MATERIALS/METHODS: Immunohistochemistry with antibodies to ERK1/2 and phosphorylated ERK (p-ERK) was performed on formalin fixed sections from 42 primary melanomas, 38 metastases, and 20 naevi. Fourteen of the primary melanomas were in the radial and 28 in the vertical growth phase. RESULTS: ERK1/2 was widely expressed (100%) in all the (pigmented) lesions studied. p-ERK1/2 expression was much lower in compound (32.4%) and dysplastic (54.5%) naevi than in primary melanoma (nodular 78.8%, superficial spreading 67%) and subcutaneous metastases (76.3%). p-ERK expression was much lower in lymph node metastases (48.5%), suggesting that the microenvironment may influence the activation of ERK. There was a (non-significant) trend for p-ERK expression to be higher in thick (>1.0 mm) versus thin (< or =1.0 mm) melanoma (p = 0.23). There was a trend for overall survival to be related to p-ERK expression in patients with melanoma over 1 mm in thickness. CONCLUSIONS: Expression of activated ERK1/2 in melanocytic lesions appears to be related to malignant potential so that activation of ERK1/2 may be important in melanoma progression. These results provide important histological support for the proposal that inhibition of this signalling pathway may be useful in treatment of melanoma.

Adolescent↗

En-bloc resection, extracorporeal irradiation, and re-implantation in limb salvage for bony malignancies.

We treated 50 patients with bony malignancy by en-bloc resection, extracorporeal irradiation with 50 Gy and re-implantation of the bone segment. The mean survivor follow-up was 38 months (12 to 92) when 42 patients were alive and without disease. There were four recurrences. The functional results were good according to the Mankin score (17 excellent, 13 good, nine fair, three failures), the Musculoskeletal Tumour Society score (mean 77) and the Toronto Extremity Salvage score (mean 81). There was solid union, but bone resorption was seen in some cases. The dose of radiation was lethal to all cells and produced a dead autograft of perfect fit. Extracorporeal irradiation is a useful technique for limb salvage when there is reasonable residual bone stock. It allows effective re-attachment of tendons and produces a lasting biological reconstruction. There should be no risk of local recurrence or of radiotherapy-induced malignancy in the replanted bone.

Adolescent↗

Melanocytic lesions of the face: diagnostic pitfalls.

The pathologist often has a difficult task in evaluating melanocytic lesions. For lesions involving the face the consequences of misdiagnosis are compounded for both cosmetic and therapeutic reasons. In this article, the pathological features of common and uncommon benign and malignant melanocytic lesions are reviewed and pitfalls in their diagnosis are highlighted. Benign lesions resembling melanomas include regenerating naevus, "irritated" naevus, combined naevus, "ancient naevus", Spitz naevus, dysplastic naevus, halo naevus, variants of blue naevi, balloon and clear cell naevi, neurotised naevus and desmoplastic naevus. Melanomas that can easily be missed on presentation include desmoplastic, naevoid, regressed, myxoid and metastatic types as well as so-called malignant blue naevi. Pathological clues to benign lesions include good symmetry, V-shaped silhouette, absent epidermal invasion, uniform cellularity, deep maturation, absent or rare dermal mitoses and clustered Kamino bodies. Features more commonly present in melanomas include asymmetry, peripheral epidermal invasion, heavy or "dusty" pigmentation, deep and abnormal dermal mitoses, HMB45 positivity in deep dermal melanocytes, vascular invasion, neurotropism and satellites. Familiarity with the spectrum of melanocytic lesions and knowledge of the important distinguishing features should assist in interpretation. Occasionally, the use of ancillary studies may also provide additional useful information. Application of standard criteria for diagnosing such lesions should enable the correct diagnosis to be established in most cases.

Diagnosis, Differential↗

Hyalinising spindle cell tumour with giant rosettes: report of a case with unusual features including original histological and ultrastructural observations.

Hyalinising spindle cell tumour with giant rosettes (HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with low-grade fibromyxoid sarcoma (LGFMS). We report a case of HSCTGR occurring in the deep soft tissues of the thigh of a 46-year-old woman, that presented as a slowly growing, painless mass. Microscopically the tumour was composed of spindled stromal cells amongst which were scattered so-called collagen rosettes. The distinctive feature of this case was the previously unreported finding of lymphoid cells of T-cell phenotype admixed with fibrohistioctyic cells in the cellular cuff surrounding the collagenous core of the rosettes. The case was further unusual in that it included focal areas of increased cellularity with a mitotic count of up to three per 10 high-power fields. While the latter feature has been associated with increased recurrences and metastases in LGFMS, it is not known whether the significance is similar in HSCTGR. The spindled stromal cells showed ultrastructural features of poorly differentiated fibroblasts, while those at the edges of the rosettes showed features of altered fibroblasts, some with a fibrohistiocytic appearance. These findings support the interpretation that HSCTGR forms part of the spectrum of sarcomas showing fibroblastic differentiation.

Aged↗

Chondrosarcoma of thumb metacarpal--a case report with literature review.

Function preserving management of a dominant thumb metacarpal chondrosarcoma is reported, with a literature review for this uncommon neoplasm. Wide local excision of the metacarpal followed by temporary silicone block interposition and definitive iliac crest bone grafting was performed. A persistent wound defect was managed by a radial artery forearm flap. The functional result was acceptable. In the literature, there were seven cases of thumb metacarpal chondrosarcoma reported; two were treated by ray amputation, and the other five were treated by excision of the metacarpal. Three of those five had bone graft and the other two had simple resection. Of these seven cases, three had local recurrence and one a distant metastasis.

Aged↗

A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions.

Differentiation between malignant melanomas and benign nevi can sometimes be difficult by conventional histopathology, and additional diagnostic markers may be helpful. This study investigated the immunoreactivity of the cell proliferation marker MIB1-Ki67 in 23 compound nevi, 17 dysplastic nevi, 8 Spitz nevi (SN), and 24 malignant melanomas (MMs) and evaluated its ability in separating benign nevi from MMs. In each lesion, the average number (percentage) of MIB1-positive nuclei (%MIB1-Mean) and the maximal number (percentage) of MIB1-positive nuclei (%MIB1-Max) were determined from each of the superficial, middle, and deep dermal zones of the lesion as well as from the entire lesion. The %MIB1-Max was determined from subjectively selected area(s) of high count. Malignant melanomas had a significantly greater %MIB1-Mean and %MIB1-Max than all benign nevi in all individual zones and in the entire lesion (p < 0.05). Discriminant analysis showed that the %MIB1-Mean and %MIB1-Max counted from the whole lesions had better discriminating abilities than from the individual zones. By using the %MIB1-Mean from all zones, all lesions except 1 SN and 3 MMs could be correctly classified as benign or malignant. When using the %MIB1-Max from all zones, all but 2 SN could be correctly separated as benign or malignant. Thus, MIB1-Ki67 immunoreactivity closely correlates with the benignancy or malignancy of melanocytic lesions and may assist in the differentiation of benign nevi from MMs.

Adolescent↗

Prevalence and distribution of ret/ptc 1, 2, and 3 in papillary thyroid carcinoma in New Caledonia and Australia.

The world's highest incidence of thyroid cancer has been reported among females in New Caledonia, a French overseas territory in the Pacific located between Australia and Fiji. To date, no molecular genetic studies in this population are available. Over the past few years, the oncogenic rearrangement of the ret protooncogene (ret/ptc) has been studied in papillary carcinomas in different populations. In this study, we investigated the prevalence and distribution of ret/ptc1, 2, and 3 in papillary thyroid carcinoma from the New Caledonian population and compared the pattern with that of an Australian population. Fresh-frozen and paraffin-embedded papillary carcinomas from 27 New Caledonian and 20 Australian patients were examined for ret rearrangements by means of RT-PCR with primers flanking the chimeric region, followed by hybridization with radioactive probes. ret/ptc was present in 70% of the New Caledonian and in 85% of the Australian samples. Multiple rearrangements were detected and confirmed by sequencing in 19 cases, 4 of which had 3 types of rearrangements in the same tumor. This study demonstrates a high prevalence of ret/ptc in New Caledonian and Australian papillary carcinoma. The findings of multiple ret/ptc in the same tumor suggest that some thyroid neoplasms may indeed be polyclonal.

Adolescent↗

Effect of melanin bleach on Feulgen-DNA microdensitometry in pigmented lesions.

OBJECTIVE: To investigate the effect of melanin bleach on Feulgen-DNA microdensitometry in pigmented melanocytic lesions. STUDY DESIGN: Twenty banal compound nevi with various grades of pigmentation were bleached by 0.5% and 1% KMnO4 for 0 to 20 minutes and by 10% H2O2 for 24 hours prior to Feulgen staining. DNA microdensitometry was performed by video image analysis to measure the integrated optical density (IOD) in nuclei from nevomelanocytes, lymphocytes and spinous keratinocytes. The DNA index of nevomelanocytes was calculated using spinous keratinocytes as the diploid controls. RESULTS: There were significant decreases in IOD (P < .05) in the nuclei of nevomelanocytes, lymphocytes and spinous keratinocytes after treatment with 1% KMnO4 for 5 and 10 minutes, but no significant changes were detected after treatment with 0.5% KMnO4 for 5 and 10 minutes. Severe tissue damage was observed in the Feulgen-stained slides treated with 1% KMnO4 for 15 and 20 minutes and with 10% H2O2 for 24 hours. There was no significant change in DNA index in any bleached sets measured. CONCLUSION: KMnO4 can affect Feulgen-DNA content if used in high concentrations or for long periods of incubation. The DNA index, which is derived from internal controls, is not affected by the bleach procedure.

Cell Nucleus↗

Method of melanin bleaching in MIB1-Ki67 immunostaining of pigmented lesions: A quantitative evaluation in malignant melanomas.

The effect of melanin bleaching on the immunoreactivity of the MIB1-Ki67 antigen in pigmented melanocytic lesions was investigated. Eight paired non-pigmented and heavily pigmented malignant melanomas (6 primary melanomas and 2 secondary melanomas) were selected. Avidin-biotin immunoperoxidase complex (ABC) and microwave antigen retrieval were used in immunostaining. Sections were incubated with 10% H2O2 for 24h before immunostaining with primary antibody MIB1, or after the completion of immunostaining. Non-bleached controls were obtained by conducting the identical staining but omitting the bleaching procedure. In all heavily pigmented lesions bleached by 10% H2O2 before or after immunostaining, the melanin was bleached effectively and MIB1-positively stained cells were clearly seen. Cell counting in the non-pigmented group found that there were no significant differences in the percentage of MIB1-positive melanoma cells (%MIB1) between non-bleached controls and those sections which had been bleached by 10% H2O2 either before or after the immunostaining. The results suggest that hydrogen peroxide can effectively bleach melanin in pigmented melanocytic lesions without significantly affecting MIB1-Ki67 immunolabelling.

Antibodies, Monoclonal↗

Analysis of histopathological factors associated with prolonged survival of 10 years or more for patients with thick melanomas (> 5 mm).

AIMS: Although tumour thickness is the best predictor of melanoma prognosis in patients with localized cutaneous melanoma, prolonged survival occasionally occurs in patients with thick melanomas (> 5 mm). This study examined histological features which were associated with long-term survival. METHODS AND RESULTS: Forty-two patients with thick, vertical growth phase melanomas surviving 10 years or more after diagnosis were matched by clinical stage of disease, sex, age and anatomical site of the primary lesion with 42 patients with similar characteristics who died from their disease within 3 years of diagnosis. Fourteen histological factors were assessed in both groups. Tumours with spindle cell and Spitz-like cell populations and those with low mitotic activity were significantly more frequently observed in long-term survivors. There was also a significant excess of melanomas exhibiting desmoplasia and those lacking vascular invasion in the long-term survivors. CONCLUSIONS: These findings suggest that it may be useful to modify the current cutaneous melanoma classification on the basis of unusual cytological characteristics (as discussed at the recent 4th World Conference on Melanoma).

Adolescent↗

Perineural fibrous thickening within the dental pulp in type 1 neurofibromatosis: a case report.

A case of type 1 neurofibromatosis is presented that illustrates oral manifestations and their role in the diagnosis of this condition. The oral lesions may be overlooked in the diagnosis of intraoral swellings. This case documents the finding of perineural fibrous thickening within the dental pulp. Such changes may indicate pulpal involvement in neurofibromatosis and the effect of a genetically transmitted disorder upon the pulp.

Adult↗

Minocycline-induced hyperpigmentation in leprosy.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

Adult↗

Cutaneous melanomas that defy conventional prognostic indicators.

Tumor thickness is usually an accurate prognostic indicator for the patient with melanoma. However, very thin primary melanomas occasionally recur locally or metastasize, whereas some patients with very thick primary melanomas survive far longer than expected. There is also a group of patients with primary melanomas of various thicknesses who relapse after a very long disease-free interval. The large database of the Sydney Melanoma Unit which now contains comprehensive long-term follow-up on more than 13,000 patients treated over a 45-year period, has provided a unique opportunity to study melanomas that defy conventional prognostic indicators. Recurrence developed in 2.8% of melanoma patients classified as stage I (pTNM staging system) and with very thin lesions (< 0.50 mm). These recurrences developed more frequently in women than men and histologically were found to be associated with ulceration, high mitotic activity, and invasion to Clark's level IV, but not with regression. Concurrent lymph node metastases (stage III) were present in 3.1% of patients with very thin lesions (< 0.50 mm). In this group, most patients were men, and every lesion displayed regression. Total survival exceeded 15 years in 15.7% of stage II and III patients with very thick lesions (> 5.5 mm). In 1.7% of patients with lesions of any thickness, the disease-free interval before relapse was > 15 years. Neither in patients with very thick lesions surviving for > 15 years, nor in those with a disease-free interval of > 15 years was it consistently possible to show the presence or absence of any of the histological features usually considered to be of prognostic significance.

Adult↗

Malignant pilomatrixoma of the scalp.

A 33 yr old man with a history of pilomatrixoma of the scalp, presented 5 mths later with a metastatic undifferentiated carcinoma in a submandibular lymph node. The cutaneous and lymph node tumors showed close histological similarity and features of malignancy. Investigations over 30 mths excluded a primary neoplasm elsewhere and consequently led to the diagnosis of malignant pilomatrixoma. These tumors are rare and most often located on the scalp. Most of the affected patients are middle age males. Wide excision is advised to avoid recurrences.

Adult↗