Allan A. Palmer

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.

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.

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

Summary 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/mm 2, 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.

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 (⩽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.

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.

Umbilical cord whole blood viscosity and the umbilical artery flow velocity time waveforms: a correlation

Summary. The possibility was examined of an association between umbilical cord whole blood viscosity and umbilical artery flow velocity time waveforms obtained with continuous wave Doppler ultrasound. The cord blood viscosity was measured at both high (100 s‐l) and low (0·1 s‐I) shear rates with a concentric cylinder viscometer. Plasma viscosity and fibrinogen were also measured. An abnormal pattern in the umbilical artery flow velocity waveform (high A/B ratio) indicative of high resistance was associated with an increase in whole blood viscosity at high shear (which may reflect a change in red cell rigidity). Viscosity at low shear (reflecting red cell aggregation and rouleaux formation) did not differ. There was a significant association between the small‐for‐gestational age fetus and abnormal umbilical artery waveform study (P <0·002) but not abnormal whole blood viscosity at high (P=0·09) or low (P=0·08) shear.

Argyrophilic Staining of Nucleolar Organizer Region Count and Morphometry in Benign and Malignant Melanocytic Lesions

Differentiation between malignant melanomas (MMs) and benign nevi based on histologic features can sometimes be difficult. This study evaluated the diagnostic effectiveness of argyrophilic staining of nucleolar organizer regions (AgNORs) in separating benign nevi from MMs by assessing 27 compound nevi (CN), 20 dysplastic nevi (DN), 10 Spitz nevi (SN), and 24 MMs. Both AgNOR count and morphology variables were measured from the superficial, middle, and deep zones of the lesions using video image analysis. Malignant melanomas had a significantly greater AgNOR number per nucleus, mean AgNOR area per nucleus, and variation in AgNOR area per nucleus compared with all types of benign nevi (p < 0.05). In multivariate discriminant analysis using a combination of four AgNOR counts and morphometric parameters, all CN and DN, 8 of 10 SN, and 23 of 24 MMs could be correctly classified as benign or malignant. The results suggest that both AgNOR count and morphology help to separate benign and malignant melanocytic lesions and that the combination of both sets of parameters improves their discriminating ability.

A comparison of some methods for identifying amelanotic and oligomelanotic melanoma metastases in paraffin sections.

&NA; Four methods were compared for identifying amelanotic and oligomelanotic melanomas in paraffin sections of formalin‐fixed metastases from subjects with primary cutaneous melanomas. Of the amelanotic and oligomelanotic metastases a characteristic pattern of fluorescence was seen with an incident‐light fluorescence microscope in 11 of 25 (44%); the Warthin‐Starry stain at pH 3.2 was positive in 14 of 25 (56%); these two procedures together were a little more effective, 63% positive; S100 protein was revealed by immunoperoxidase staining in 26 of 28 (93%); the monoclonal antibody NKI/C‐3 against a human melanoma antigen gave positive immunoperoxidase staining in 24 of 27 cases (89%). Of the pigmented metastases S100 protein was demonstrated in 18 of 21 (86%) and NKI/C‐3 gave positive staining in all 20 tested. These antibodies are not specific for melanoma but a metastasis which does not react with either antibody is unlikely to be melanoma.

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 34βE12) 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).

Intramuscular dendritic fibromyxolipoma: Myxoid variant of spindle cell lipoma?

Dendritic fibromyxolipoma (DFML) is an uncommon, recently described, benign soft tissue lesion that shares many clinical and pathological features with myxoid variants of spindle cell lipoma (SCL). As described, DFML is distinguished from SCL by the presence of dendritic cytoplasmic processes, abundant keloidal collagen and a prominent, often plexiform vascular pattern. We describe the first known reported case of an intramuscular DFML that occurred in the right shoulder region of a 73‐year‐old man. The tumor displayed the typical histopathological features of DFML but also included foci of chondroid metaplasia, a previously unreported finding. This report also discusses the differential diagnosis, particularly distinguishing DFML from SCL and myxoid liposarcoma. In view of the similarities in many clinical and pathological features between SCL and DFML, we speculate that DFML probably represents an unusual variant of myxoid SCL.