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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.

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.

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.

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.

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.

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.

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.

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.

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.

Of 57 reviewed cases of malignant melanoma in teenagers, 51 had a minimum follow-up of 5 years. The histological and some clinical features of the 51 cases were compared for diagnostic and prognostic significance with those of 19 Spitz naevi and 10 other benign naevi using the SPSS-X computer program. The overall crude survival was 71% (males 64%, females 81%). Five patients with regional metastases survived more than 5 years, three of these more than 10 years. The main statistically significant features associated with a poor prognosis were Breslow thickness, diameter of ulcer, abnormal mitoses, pushing dermal borders and marginal (deep) mitoses. In comparison with Spitz naevi, features favouring malignancy were Breslow thickness, fine dusty cytoplasmic melanin pigment, marginal or abnormal mitoses, epithelioid intra-epidermal melanocytes below parakeratosis, dermal nests larger than junctional nests and the mitotic rate in the papillary dermis. Features favouring a benign lesion were diffuse maturation, spindle cells, spindle nuclei and Kamino bodies, especially if numerous or clustered. In comparison with the atypical benign naevi, significant features favouring malignancy were marginal or abnormal mitoses, single cell epidermal invasion below parakeratosis, large nuclei and irregular nuclei.

Adamantinoma is a rare tumor of the appendicular skeleton, and only six cases of ulnar involvement have been reported. We present the case of a 58-year-old man who sustained a pathologic fracture of the proximal third of this right ulna. Biopsy at the time of intramedullary fixation revealed adamantinoma, and he was referred for treatment. There was no evidence of metastatic disease. At operation, the proximal 22 cm of ulna was excised en bloc and the defect reconstructed using a vascularized fibular osteoseptocutaneous flap. The postoperative course was uneventful, and the patient has remained free of disease with very good function 3 years later.

The New South Wales Bone Tumour Registry records for malignant fibrous histiocytoma were reviewed. Thirty-eight cases were available for analysis, representing 8% of the 506 malignant bone tumours reported to the Registry over 15 years (1977-91). The review confirmed that malignant fibrous histiocytoma is a high-grade primary bone sarcoma occurring in a wide age range in a bimodal distribution. Tumours mainly occurred around the knee or the ends of other long bones. Twenty-six per cent of cases arose in a pre-existing lesion, 4 cases post-radiotherapy, 3 cases in Paget's disease, 2 cases in bone infarcts and 1 case each in osteoblastoma, osteosarcoma and giant cell tumour. Thirty-two patients were treated by amputation or wide excision and in 11 patients this was preceded by intralesional curettage. Three patients had marginal resections and three had no surgery. Five year survival was 53% overall. Age at presentation significantly affected survival; patients under 55 years had a 5 year survival rate of 70%, compared with 19% for patients over 55 (P < 0.05). Survival was 86% at 5 years if the initial procedure was radical or wide, but only 30% if marginal or intralesional (P < 0.01). Adjuvant chemotherapy as an isolated factor did not affect survival. Rigorous adherence to the principles of surgical staging and biopsy was found to be the most successful way to treat malignant fibrous histiocytoma of bone.

The Cancer Registries have been operational in the South Pacific since 1958 (Papua New Guinea), Fiji (1965) and New Caledonia (1977) and complete cancer incidence rates are available, based on histologic data. We studied 97 melanomas, histologically confirmed, which were diagnosed in New Caledonia from 1973 to 1991. New Caledonia is located in the same latitude as Queensland in Australia, known for having the highest incidence of melanoma in the world. Standardised incidence rates (world population) were 9.82 and 7.65/100,000/year for European males and females, compared to 1.65 and 1.05 for Melanesian and Polynesian males and females. The European population is exposed and Melanesians/Polynesians are relatively protected as are black Americans or Africans. The mixed populations are protected, but no study is available as to the exact proportion of mixed people (20%?) in the entire population. For Europeans, among males, the main areas in which melanomas occur are the trunk (45%) the arm (13%) and the leg (13%). Among females, the main areas are the leg (27%), the trunk (20%) and the head (18%). Screening for melanoma has been more effective in the last 6 years, a period in which we diagnosed half the total cases and generally at earlier stages. Prognosis was poor for this period (1973-1991): the five year survival rates were 64% +/- 8%, not as good as in Europe or Australia, but these lesions were diagnosed between 1973 and 1985 and were generally more invasive. A better prognosis will probably be observed in a few years, and another evaluation of melanoma screening should be made in the future as well the study of precursors and early lesions.