Lentigo maligna and malignant melanoma in situ, lentigo maligna type.

Some authors have considered lentigo maligna to be an atypical melanocytic proliferation, whereas others have considered it to be melanoma in situ. We reviewed 50 cases of lentigo maligna. We have identified two subsets of lesions. The first has atypical melanocytic hyperplasia, which we postulate to be correctly designated lentigo maligna. The second subset has the following features in addition to the melanocytic hyperplasia: individual and nests of cells at varying layers of the epidermis, confluence of the melanocytes replacing the basilar region, uniformity of the cytological atypia, and nesting of uniformly atypical melanocytes. These lesions we designate as malignant melanoma in situ, lentigo maligna type. We are proposing that the lesions that have been termed lentigo maligna represent a spectrum of atypia and that the application of some of the traditional features for the diagnosis melanoma may permit the segregation of more and less aggressive lesions.     

Angiocentric invasion by lentigo maligna melanoma.

A case of angiocentric invasion by a lentigo maligna melanoma is reported. Pericapillary cuffing and permeative intimal expansion of veins by melanoma without luminal tumour cell emboli, thrombosis, or vascular destruction were associated with a lentigo maligna melanoma on the face of a 93 year old woman. This unusual infiltrative pattern suggests a specific interaction between melanoma cells and perivascular connective tissue elements, and may imply expression by tumour cells of receptors for molecules in the intima of blood vessels and in pericapillary stroma.     

Dermal vascularity in lentigo maligna

Lentigo maligna (LM) may represent a tumour arrested in an in situ phase, lacking the angiogenic capacity and underlying dermal neovascularization required for invasive growth. The acquisition of an angiogenic phenotype might be associated with the development of lentigo maligna melanoma (LMM). To investigate this thesis, sections of formalin-fixed, paraffin-embedded tissue from 15 LMMs, and 11 LM excision specimens were stained with the vascular endothelial marker Ulex europaeus agglutinin I. Dermal vessels were counted and vascular morphometry was performed. In specimens in which LMM was present, dermal vascularity was significantly increased in LM compared with normal skin. The most significant increases were found for dermal vascular density (39 per cent increase, P=0.008) and for total vessel surface area (62 per cent increase, P=0.005). However, when no LMM was present, the vascular density underlying LM (79 ± 9 vessels/mm²) did not differ significantly from that of adjacent normal skin (67 + 6 vessels/mm²), although focal ‘hot spots’ of increased vascularity were present. We conclude that increased dermal vascularity is present beneath in situ LM and that this increased vascular density is closely associated with the presence of invasive LMM in the same specimen.     

Immunohistochemical study of melanocytic differentiation antigens in cutaneous malignant melanoma. A comparison of six commercial antibodies and one non-commercial antibody in nodular melanoma, superficially spreading melanoma and lentigo maligna melanoma

In certain primary and metastatic malignant melanomas diagnostic problems may arise due to their cytologic features and/or absence of synthesis of melanin. As the "classic" combination of S-100 protein and HMB-45 may occasionally fail to stain cells of malignant melanoma, we have tested a series of commercially accessible antibodies which were so far not compared by other authors in the three most frequent subtypes of this tumor. In surgical specimens from 104 cutaneous malignant melanomas (40 nodular melanomas, 46 superficially spreading malignant melanomas and 18 lentigo maligna melanomas) the staining intensity and the proportion of neoplastic cells stained with antibodies to S-100 protein, HMB-45, NKI/C3, NKI/beteb, MART 1 (Melan A), KBA 62 and Mitf was semiquantitatively analysed. The use of this group of antibodies against melanoma-associated antigens revealed it to be a favourable supplement for the bioptical or cytological diagnosis of malignant melanoma in case the traditional/conventional combination of S-100 protein and HMB-45 antibody fails. According to the authors' experience the antibody against KBA 62 has shown to be the most effective antibody followed by the antibodies against MART-1 (Melan A) and NKI/C3.     

Ultrastructure of lentigo maligna in the oral cavity

A rare case of lentigo maligna in the oral cavity was investigated by light and electron microscopy. Cutaneous lentigo malignas often develop to malignant melanomas. However, the electron microscopic examination revealed that even though there were a large number of melanosomes, most of them were late stage and had membrane structure, and positive staining with HMB-45 was not recognized. From our findings, it is difficult to conclude that oral lentigo malignas develop malignant melanomas, and thus further studies are needed.     

Malignant melanoma in situ: the flat, curable stage of malignant melanoma

Malignant melanoma can be diagnosed clinically and histologically when it is small, flat, and confined to the epidermis. The criteria for the diagnosis are described. The application of these criteria can lead to simple excision of the lesion and the prevention of the malignant melanoma from evolving into a neoplasm with the potential for metastasis.     

The diagnosis of Hutchinson's melanotic freckle (lentigo maligna) in Queensland

Following an increase in the reported incidence of melanoma of Hutchinson's melanotic freckle type (HMFM) in Queensland, a review of its histological diagnosis was undertaken. Ninety-nine pigmented lesions reported by 13 different pathology laboratories throughout Queensland as having an in-situ component of Hutchinson's melanotic freckle (HMF) were reviewed by 2 pathologists with an interest in malignant melanoma. This diagnosis was confirmed in 76 cases while in a further 3 the reviewers regarded the in-situ component as indeterminate. It would seem that the level of agreement among pathologists reporting HMF(M) should be considered in any assessment of incidence patterns of melanoma.     

A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. The consequences of a reclassification of the original group of lentigo maligna melanomas.

A selected series of primary malignant melanoma of the skin, clinical stage I, was originally classified according to Clark's system. The consistency of this classification was tested by two Brisbane pathologists who indicated that we had misinterpreted some cases of superficial spreading malignant melanoma as lentigo maligna melanoma. We have therefore reclassified the original group of 86 lentigo maligna melanomas. This resulted in a total series of 37 (5.5%) lentigo maligna melanomas, 301 (45%) superficial spreading malignant melanomas, 194 (29%) nodular malignant melanomas (unchanged) and 137 (20.5%) unclassifiable malignant melanomas. The diagnosis of lentigo maligna melanoma was not made unless the epidermis was atrophic and dermal solar elastosis was present. The new group of lentigo maligna melanomas is dominated by cases on the head among patients over 50 years of age (especially women). This is in better agreement with other studies than our previous findings. The relationship with tumour cell type, pigmentation, mitotic count, atypia, transsectional profile, level of invasion, ulceration, vascular invasion, lymphocyte infiltration and prognosis shown by the new groups of lentigo maligna melanoma and superficial spreading malignant melanoma indicates that the cases by which the diagnosis has been changed are relatively benign. Our previous conclusions are still valid. The lentigo maligna melanoma is still the most benign type and nodular malignant melanoma still the most malignant type of melanoma. The superficial spreading malignant melanoma still represents an intermediate tumour type, although it has deviated in the benign direction.     

Lentigo maligna and superficial spreading melanoma are different in their in situ phase: an immunohistochemical study

Clinical and pathologic observations have prompted the categorization of malignant melanoma into 4 subtypes. Although some authorities challenge the value of this classification, nevertheless it is generally accepted that lentigo maligna (LM), or melanoma on sun-damaged skin, has a different biological behavior than so-called superficial spreading melanoma (SSM), at least in the early stage of its evolution. To characterize some aspects of this different behavior, the in situ phase of SSM and LM was studied using immunohistochemical methods. Seventeen cases of SSM in situ and 13 cases of LM were chosen for the study. All cases qualified with strict histologic criteria. Sections from these lesions were stained with antibodies against HMB-45 antigen, basic fibroblast growth factor (bFGF), proliferating cell nuclear antigen (PCNA), and factor VIII. Semiquantitative analysis was performed. Cases classified as either LM or SSM corresponded well to the epidemiologic and clinical characteristics as described in the literature; that is, LM appeared in older patients and occurred mostly on the face, whereas SSM occurred mostly on the trunk and lower limbs. Although no difference in HMB-45 stain was observed, melanoctyes of SSM showed greater proliferative activity, as reflected by PCNA stain (P < 0.02) and higher levels of bFGF (P < 0.001), than melanocytes of LM. More blood vessels were counted under SSM than under LM (P < 0.05). These results are in accordance with the biological behavior of SSM and LM, that is, the longer in situ phase of the latter. bFGF is both a growth factor for melanocytes and an angiogentic factor. The differences in PCNA, a proliferation marker, and blood vessel count may be related to the bFGF effect. Thus this study reveals some of the biological differences between LM and SSM. Location and sun exposure habits may contribute to these differences, which already exist in the in situ phase.     

Angiomatoid melanoma: a novel pattern of differentiation in invasive periocular desmoplastic malignant melanoma

A case of locally invasive, long-standing desmoplastic and amelanotic malignant melanoma is described in an 84-year-old man. Histologic examination of the involved periorbital tissue showed neoplastic foci exhibiting a novel pattern reminiscent of microvascular proliferation. These regions were characterized by malignant, S-100-positive tumor cells lining vessel-like spaces in transverse sections and forming tubuler-like structures in longitudinal sections. Recent data indicate that melanoma cells may express genes and patterns of differentiation in vitro akin to endothelial cells. Because angiosarcoma often involves facial and scalp skin of elderly individuals, awareness of angiomatoid differentiation in melanoma has important diagnostic implications. HUM PATHOL 31:1520-1522.     

Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ

Primary malignant melanoma is an unusual lesion in the esophagus that is not infrequently seen in association with melanosis. A case of esophageal invasive malignant melanoma with melanosis is described in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ. The authors know of no previously reported such finding.     

Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ.

Dermatofibromas are common lesions that are often associated with epidermal hyperplasia and basal layer hyperpigmentation. A single case of lentiginous melanocytic hyperplasia overlying a dermatofibroma has been reported, however, nevi and melanoma have to the best of our knowledge, not been previously reported. We present 14 cases of melanocytic lesions associated with dermatofibromas. The clinical data and hematoxylin- and eosin- stained sections were obtained and formalin-fixed, paraffin-embedded tissue was immunostained with antibodies against S-100, Mart-1, Factor XIIIa, and CD117. There were nine females and five males ranging in age from 30 to 64 years and anatomic sites included back (five), arm (six), flank (two), and leg (one). The clinical diagnosis ranged from dermatofibroma to desmoplastic melanoma. Histologically, the melanocytic lesions included junctional, compound, and dermal nevi, and malignant melanoma in situ. In four cases the dermal component appeared to merge with the dermatofibroma. In the case of the melanoma in situ, the dermatofibroma abutted the epidermis. Immunohistochemically, the melanocytic lesions were S-100/ Mart-1+, FXIIIa-, and the dermatofibromas were S-100/Mart-1-, FXIIIa+. Melanocytic neoplasia may appear in association with dermatofibromas. The fibrohistiocytic proliferation may be misinterpreted as a spindle or pleomorphic melanocytic process. Awareness of this association will aid in the correct diagnosis, and immunohistochemical studies will help in the differentiation of these two cell populations.     

Malignant melanoma in situ

There is general agreement that there are lesions which should be diagnosed as malignant melanoma in situ. The biologic behavior of the intraepidermal component of superficial spreading melanoma (the radial growth phase) has been demonstrated to have significantly different properties than those of the cells in the vertical growth phase. The central controversies regarding malignant melanoma in situ relate to the criteria for diagnosing melanoma and whether there are atypical melanocytic lesions which are neither nevi nor melanoma. I propose that reliable and reproducible objective criteria for melanoma have not been developed; rather, dermatopathologists use differing subjective criteria which result in diagnostic agreement in the vast majority of lesions. The controversy is over those lesions which are classified as melanoma by one set of criteria and not by others. I am also a proponent of the diagnosis of atypical melanocytic lesions, and have suggested an analogy to keratinocytic lesions in which this concept is well established. Studies of the sensitivity and specificity of the correlation between clinical and histologic features and the biologic behavior of melanocytic lesions are necessary to resolve these issues.     

Tyrosinase expression in malignant melanoma,desmoplastic melanoma,and peripheral nerve tumors

CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45. CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.