Interobserver reproducibility of histopathologic prognostic variables in primary cutaneous melanomas.

BACKGROUND: The prognosis for patients with localized primary cutaneous melanoma is known to depend principally on tumor thickness, and to a lesser extent on ulcerative state and Clark level. We have recently found in an analysis of 3661 patients that tumor mitotic rate (TMR) is also an important prognostic parameter, ranking second only to tumor thickness. However, few studies have assessed the accuracy and reproducibility with which these features of a melanoma are recorded by histopathologists. AIM: To assess interobserver reproducibility of major pathologic prognostic parameters in cutaneous melanoma. METHODS: Single hematoxylin and eosin-stained slides of 69 dermally invasive primary cutaneous melanomas were circulated among six pathologists with differing experience in the assessment of melanocytic tumors. The observers independently determined the tumor thickness, Clark level of invasion, ulcerative state, and TMR for each lesion. Intraclass correlation coefficients and kappa scores for multiple ratings per subject were calculated. RESULTS: The intraclass correlation coefficients were 0.96 for tumor thickness and 0.76 for TMR. The kappa scores were 0.83 for ulcerative state and 0.60 for Clark level. These results indicated excellent agreement among the pathologists for measurements of tumor thickness, ulcerative state, and TMR and fair to good agreement for Clark level. CONCLUSIONS: Appropriately trained and experienced histopathologists can assess prognostically important features of melanomas accurately and reproducibly. Given our recent finding of the significance of TMR in determining prognosis, it is important that this feature be assessed by a standardized method and documented for all primary cutaneous melanomas.

Desmoplastic melanoma: a diagnostic trap for the unwary.

Desmoplastic melanoma (DM) is an uncommon type of spindle cell melanoma in which the malignant cells are separated by collagen fibres or fibrous stroma. DM is prone to misdiagnosis because of unfamiliarity with its often bland appearance and dissimilarity to other conventional types of melanoma. It displays variable cytological atypia, cellularity and stromal fibrosis and more often than not has an accompanying atypical junctional component. Neurotropism is a common associated feature (in at least 30% of cases) and when it occurs such tumours are termed 'desmoplastic neurotropic melanomas' (DNM). The neurotropism may be perineural or intraneural and often extends beyond the desmoplastic component. In addition, some DMs show evidence of neural differentiation ('neural transformation'). DM may also present as a recurrence or occasionally as a metastasis from other types of melanoma. A high index of suspicion and knowledge of its often subtle morphological appearance are necessary to avoid misdiagnosis.

Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?

Spitz naevus is a benign melanocytic lesion that shares many histological features with melanoma. While Spitz naevi characteristically occur in children and young adults and melanomas in the middle-aged and elderly, either tumour can occur in patients of any age. In many cases, the histopathological diagnosis of Spitz naevus is straightforward, particularly in small lesions displaying many or all of the typical histological features and occurring in young patients. Tumours that deviate from the classic description, however, cause difficulties in diagnosis. In this review, we highlight histopathological features of Spitz naevi and those that may be useful in distinguishing Spitz naevi from melanomas. We find that the presence of good symmetry, Kamino bodies, and uniformity of cell nests or sheets from side-to-side favours a Spitz naevus. The presence of abnormal mitoses, a dermal mitotic rate of >2/mm2, and mitotic figures within 0.25 mm of the deep border of the lesion favours a melanoma. Immunohistochemical stains for HMB45 and Ki67 sometimes provide additional useful information. Despite this, in some cases it may not be possible to give an unequivocal diagnosis. Recommendations for the reporting of such cases are provided. New techniques have also demonstrated chromosomal, molecular and genetic differences between Spitz naevi and melanomas. This report highlights these new data and speculates on their possible future role in the diagnosis of borderline lesions.

Combined naevus: a benign lesion frequently misdiagnosed both clinically and pathologically as melanoma.

BACKGROUND: Combined naevi are characterised pathologically by the presence of two or more different types of melanocytic naevi in a single lesion. They are prone to clinical and pathological misdiagnosis as melanoma. Misdiagnosis may result in inappropriate treatment, patient anxiety and medicolegal consequences. AIMS: With the aim of reducing the incidence of misdiagnosis, this study documents the clinical and pathological features of a large series of combined naevi and describes how to distinguish them from melanoma. PATIENTS AND METHODS: The slides of skin lesions from 220 patients that were coded as combined naevus between 1990 and 2001 were retrieved from the archival files of the Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia. The clinical notes, letters from referring pathologists (for consultation cases) and slides were reviewed and for each lesion clinical and pathological features were assessed. Thirty-eight cases were excluded either because they included only one naevus component or because there were atypical pathological features in the slides available for review. The remaining 182 cases formed the study population. RESULTS: The patients included 92 females and 87 males (1.1:1). In three cases the gender was not known. Mean and median patient ages were 29.6 and 28 years, respectively. The anatomical site of involvement was the trunk in 64 cases (35.2%), head and neck region in 43 cases (23.6%), upper extremity in 40 cases (22.0%), lower extremity in 18 cases (9.9%) and perineum and buttock region in eight cases (4.4%). In nine cases the site of involvement was not known. A pre-operative clinical diagnosis was recorded in 126 cases; of these, melanoma was suspected clinically in 33 cases (26.2%) while combined naevus was diagnosed clinically in only three cases (2.4%). Histologically, 180 cases included two different naevus components, and in two cases three different naevus components were present. The most common combination was a common acquired naevus of compound type associated with a blue naevus of deep penetrating naevus type; this occurred in 57 cases (31.3%). The referring pathologist recorded a preferred diagnosis in 88 of 122 consultation cases; of these, melanoma was suspected in 23 cases (26.1%) and in 23 cases combined naevus was favoured (26.1%). CONCLUSIONS: Combined naevus is an uncommon type of melanocytic naevus that is frequently misdiagnosed both clinically and pathologically. Knowledge and recognition of the pathological features of combined naevi and the important features that distinguish them from melanomas should reduce the frequency of misdiagnosis.

Parachordoma is not distinguishable from axial chordoma using immunohistochemistry.

Parachordoma is a rare soft tissue tumor that morphologically resembles chordoma of the axial skeleton but occurs in a peripheral site. A recent study reported immunohistochemical differences between chordoma and parachordoma. While both tumors were positive for cytokeratin (CK) 8/18 (as recognized by the antibody Cam5.2), S100 and epithelial membrane antigen (EMA), only the chordoma was positive for CK7, CK20, CK 1/5/10/14 (as recognized by the antibody 34betaE12) and carcinoembryonic antigen (CEA). It has since been suggested that tumors indistinguishable from chordoma that involve the periphery should be termed chordoma periphericum and that these tumors are distinct from parachordoma. In the current study, the clinical, radiological, pathological, immunohistochemical and ultrastructural features of a chordoma-like tumor involving the deep soft tissues of the lower leg of a 69-year-old woman are presented. Microscopically, the tumor had a pseudolobulated growth pattern and consisted of sheets, nests and cords of epithelioid cells, some with a physaliferous appearance, separated by abundant myxoid stroma. The tumor cells were positive for CK 8/18, EMA and S100, showed focal staining for CK7, and were negative for CK20, CK 1/5/10/14 and CEA. On the basis of these results a diagnosis of parachordoma was favored. For comparison, an immunohistochemical analysis of five axial chordomas was also performed. The chordomas showed positivity for CK 8/18 (5 of 5 cases), EMA (5 of 5 cases), S100 (5 of 5 cases), CK 1/5/10/14 (1 of 5 cases) and CK7 (1 of 5 cases). Stains for CK20 and CEA were negative in all five chordomas. The results of the present study suggest that the expression of antigens for CK 1/5/10/14, CK7, CK20 and CEA in chordoma might not be as common as what has been previously reported. The results also suggest that parachordoma might not be easily distinguished immunohistochemically from axial chordoma (and therefore also from so-called chordoma periphericum).