A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. 4. The relation of cross-sectional profile, level of invasion, ulceration and vascular invasion to tumour type and prognosis.

A selected series of 669 primary cutaneous malignant melanomas, stage I, was studied. The series includes 86 lentigo maligna melanomas, 259 superficial spreading malignant melanomas, 194 nodular malignant melanomas and 130 unclassifiable malignant melanomas. The cross-sectional profile, level of invasion, ulceration and vascular invasion were graded. The relation of these features to each other and to tumour type was studied by X2 tests. The prognostic value was also studied. The most common finding was a slightly elevated surface, level III of invasion, no ulceration and no vascular invasion. Most of these tumours were superficial spreading malignant melanomas. A good prognosis was associated with a flat cross-sectional profile, level II of invasion, no ulceration and no vascular invasion. A poor prognosis was associated with marked protrusion of the surface, level IV--V of invasion, ulceration and vascular invasion. Lentigo maligna melanomas tended to be more benign while nodular malignant melanomas tended to be more malignant than the average. A superficial spreading malignant melanoma could vary in either direction. The prognostic value of level of invasion and ulceration was found to be greater than that of tumour type. The prognostic importance of invasion no further than level III is stressed. Level of invasion ought to be reported to the clinician as well as the tumour type.     

Partial regression in thin primary cutaneous malignant melanomas clinical stage I

Summary 486 patients with primary cutaneous malignant melanoma clinical stage I were examined in order to evaluate the prognostic importance of partial regression in thin lesions. All the melanomas measured 1 mm or less in maximal thickness. The study showed that past regression with fibrotic scar tissue adversely affected survival in patients with thin melanomas. The 10 year survival was 95% for patients without regression in contrast to 79% for patients with past regression. It was, furthermore, demonstrated that active regression without fibrotic scar tissue did not influence survival significantly.The wider and the thicker the fibrotic area, the poorer the survival. Although the prognostic importance of this finding was not statistically significant, we suggest that the horizontal width of the fibrotic area in particular may be a valuable prognostic guide in thin melanomas with past regression.     

A retrosepctive histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. 6. The relation of dermal solar elastosis to sex, age and survival of the patient and to localization, histological type and level of invasion of the tumour

A selected series of primary malignant melanoma of the skin, clinical stage I, was studied. The series includes 37 lentigo maligna melanomas, 301 superficial spreading malignant melanomas, 194 nodular malignant melanomas and 137 unclassifiable malignant melanomas. Dermal solar elastosis was graded. The most common finding was lack of solar elastosis which together with slight elastosis was mostly found on the trunks of young men and on the legs of young women in cases of superficial spreading malignant melanoma. Marked and moderate elastosis was found almost exclusively on the head, especially in old women with lentigo maligna melanoma. Nodular malignant melanoma was related neither to any special grade of solar elastosis, nor to localization, but showed some relation to the male sex after 50 years of age. The present study does not permit any conclusions to be made about a possible causal relationship between the three types of malignant melanoma and previous sun-exposure, because of lack of clinical information and a control series concerning solar elastosis in the normal population. Level of invasion and prognosis of the patient did not show any covariation with grade of solar elastosis.     

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.     

Therapeutic and clinico-pathological factors in the survival of 1,469 patients with primary cutaneous malignant melanoma in clinical stage I

Summary Therapeutic and clinico-pathological data of 1,469 patients with clinical stage I malignant melanoma of the skin without histological evidence of fibrotic areas of regression were examined by multivariate regression analysis. In accordance with a previous analysis anatomical site of tumour, tumour thickness, level of invasion, mitotic rate, ulceration, lymphhocytic reaction, dominant type of invasive tumour cell, and sex were found to act as independent risk factors. The present analysis, furthermore, showed that size of resection margin, diagnostic biopsy, removal of the deep fascia, age at surgery, as well as presence and depth of nevus cells did not influence prognosis when adjusting for the independent risk factors.     

Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm

Although wide surgical excision is the accepted treatment for thin malignant melanomas, there is reason to believe that narrower margins may be adequate. We conducted a randomized prospective study to assess the efficacy of narrow excision (excision with 1-cm margins) for primary melanomas no thicker than 2 mm. Narrow excision was performed in 305 patients, and wide excision (margins of 3 cm or more) was performed in 307 patients. The major prognostic criteria were well balanced in the two groups. The mean thickness of melanomas was 0.99 mm in the narrow-excision group and 1.02 mm in the wide-excision group. The subsequent development of metastatic disease involving regional nodes and distant organs was not different in the two groups (4.6 and 2.3 percent, respectively, in the narrow-excision group, as compared with 6.5 and 2.6 percent in the wide-excision group). Disease-free survival rates and overall survival rates (mean follow-up period, 55 months) were also similar in the two groups. Only three patients had a local recurrence as a first relapse. All had undergone narrow excision, and each had a primary melanoma with a thickness of 1 mm or more. The absence of local recurrence in the group of patients with a primary melanoma thinner than 1 mm and the very low rate of local recurrences indicate that narrow excision is a safe and effective procedure for such patients.     

Primary mucosal malignant melanoma: an immunohistochemical study of 12 cases with comparison to cutaneous and metastatic melanomas

Immunohistochemical analysis of 40 formalin-fixed, paraffin-embedded malignant melanomas (12 primary mucosal, 16 primary cutaneous, and 12 metastatic cutaneous) was performed to study the possible differences in immunostaining profiles according to location. The majority of melanomas were reactive with a polyclonal antibody to S100 protein (P-S100; 85%), a monoclonal melanoma-specific antibody (HMB-45; 88%), and a monoclonal antibody to vimentin (90%), and there were no differences in staining profiles for these antibodies by anatomic location. In contrast, while 13 of 16 cutaneous melanomas (81%) and ten of 12 metastatic melanomas (83%) were reactive with a monoclonal antibody to S100 protein (MoAb-079), only five of 12 mucosal tumors (42%) showed positive staining for MoAb-079. Similarly, 14 cutaneous melanomas (88%) and 11 metastatic melanomas (92%) showed positive staining for neuron specific enolase (NSE), while only four mucosal melanomas (33%) were NSE-positive. Of the 40 melanomas, all but two were reactive with either P-S100, MoAb-079, or HMB-45. These findings suggest that MoAb-079 and NSE may be less sensitive markers than P-S100 and HMB-45 for routinely processed mucosal melanomas as compared with cutaneous and metastatic tumors.     

Histologic classification of tumor-infiltrating lymphocytes in primary cutaneous malignant melanoma. A study of interobserver agreement

The density and distribution of lymphocytes infiltrating the vertical growth phase of primary cutaneous melanomas has been suggested by several studies to be of prognostic significance. However, few pathologists comment on tumor-infiltrating lymphocytes (TILs), and there is the perception that the assessment of TILs is subject to great interobserver variability. We studied interobserver agreement on the categorization of TILs; 20 cases of primary cutaneous malignant melanoma with a vertical growth phase component were circulated among 3 pathologists and 3 dermatologists. For each case, TILs were classified as brisk, nonbrisk, or absent according to Clark. Only 1 pathologist (a dermatopathologist) was familiar with the classification of TILs. Observers were given written guidelines and a brief tutorial before their examination of the slides. Our results show that with little instruction, overall agreement among observers was good (kappa values, 0.6 or more), especially among pathologists (kappa values, > 0.7). Three observers had excellent agreement among each other (kappa values, > 0.75). These findings suggest that the categorization of TILs can be easily taught and can be applied with an acceptable level of reproducibility in routine diagnostic practice.     

A histological comparison of cutaneous malignant melanoma between the Oxford Region and Western Australia

Two series of cutaneous malignant melanoma (CMM), one from a low incidence area (the Oxford Region) and one from a high incidence area (Western Australia), were compared by one pathologist using the same histological criteria. The findings included similarities in the distributions of histogenetic type of CMM, predominant cell type, and the degree and pattern of inflammatory reaction. Differences were found in other features including tumour profile, the presence of ulceration, mitotic activity, evidence of regression and level of invasion. The most important, and consistent morphological difference was the greater thickness of tumours from the Oxford Region, which is thought to be consistent with the theory that CMM is diagnosed at an earlier stage in high incidence areas because of greater medical and public awareness of the condition. Some problems in the use of accepted classifications of CMM are discussed.     

Desmoplastic malignant melanoma. A clinicopathologic study of 14 cases

Clinical and pathologic details in 14 cases of desmoplastic malignant melanoma were reviewed. The study group included ten men and four women with a median age of 58 years. Anatomic locations such as the head and neck area (four cases), limbs (five cases), and trunk (five cases) were involved with equal frequency. Follow-up information (median period, 4.6 years) was available for 12 patients, of whom four are alive and disease free, six have had local tumor recurrence, and two have died of their disease. Histologically, these lesions consisted of a malignant fibroblastic skin tumor intimately associated with a superficial melanoma (ten cases) or melanocytic dysplasia (four cases) that often extended deeply to the subcutaneous fat. Helpful diagnostic features included the presence of neurotropism, a lymphocytic infiltrate, and unusual patterns of triangular and periadnexal lamellar fibroplasia. Of the immunohistochemical markers employed, antisera to S100 protein and vimentin yielded the most consistent positive results. Immunostaining with NK1/C-3 (antimelanoma monoclonal antibody) was not helpful. Ultrastructural evidence of fibroblastic and schwannian differentiation was seen. We conclude that the altered morphologic melanomas is associated with a relatively favorable prognosis and believe that careful attention to light microscopic detail with immunohistochemical and electron microscopic assistance will elucidate the diagnosis in most cases.     

Sinonasal malignant melanoma. A clinicopathologic and immunohistochemical study of 14 cases.

The clinical, light microscopic, and immunohistochemical features of 14 sinonasal malignant melanomas were studied to show their diverse morphologic appearance and distinction from therapeutically more amenable neoplasms that occur in this region. The tumors arose in 6 men and 8 women (median age, 70 years). Eleven patients died of disease 7 to 44 months (median, 18 months) after diagnosis. The absolute median survival time was 18.5 months (range, 7 to 44 months). The predominant microscopic appearance was categorized as small blue cell in eight cases, spindle cell in three cases, epithelioid in two cases, and pleomorphic in one case. Eight tumors had multiple patterns. Five sinonasal malignant melanomas had theque-like growth, five had junctional change, and 10 contained at least rare melanin pigment. Fourteen, 13, and 12 sinonasal malignant melanomas were immunoreactive with anti-vimentin, HMB45, and anti-S100 protein antibodies, respectively. One epithelioid tumor positive for vimentin, S100, and HMB45 also contained scattered epithelial membrane antigen-positive and cytokeratin-positive cells, which emphasizes the need for a battery of stains to distinguish sinonasal malignant melanoma from carcinoma. All tumors were negative for leukocyte common antigen, muscle-specific actin, and synaptophysin. Diffuse immunopositivity for vimentin, S100 protein, and HMB45 allows distinction of sinonasal malignant melanomas from histologically similar neoplasms.     

Subacute cutaneous lupus erythematosus—the annular variant. A histological and ultrastructural study of five cases

Subacute cutaneous lupus erythematosus is an uncommon, non-scarring variant of lupus erythematosus which has received scant attention in the pathology literature. Its recognition as a distinct entity is important, as, although mild systemic features may be associated, there is characteristically a relative absence of life-threatening renal or central nervous systemic involvement. Subacute cutaneous lupus erythematosus may be clinically sub-divided into the more common annular and the rarer papulosquamous (psoriasiform) variants. A clinicopathological study of five cases of the annular variant is presented with a review of the literature. We highlight the histological and ultrastructural appearances. Discriminatory features from the other variants of lupus erythematosus and additional conditions with which it may be confused, including lichen planus and acute graft-versus-host disease, are discussed.     

Survival from invasive cutaneous malignant melanoma in Western Australia and the Oxford Region: a comparative histological study of high and low incidence populations

A detailed histological review of 196 cases of invasive cutaneous malignant melanoma diagnosed in Western Australia, a high incidence area, during 1975-76 and of 226 cases during the period 1972-76 from the Oxford Region, a low incidence area, was made by one pathologist using the same parameters for each series. Five-year survival rates were analysed with respect to histological features, sex and site, with and without correction for tumour thickness. The results showed higher overall survival rates in Western Australia, with marked differences in prognosis between males and females in the Oxford Region, and between Oxford males and patients of both sexes in Western Australia. These findings were in accord with the corresponding differences in tumour thickness, and they support the theory that survival rates from cutaneous malignant melanoma are higher in areas of high incidence because they are diagnosed and treated earlier.     

Papillary adenocarcinoma of the endometrium: a retrospective study of stage I and II disease.

A retrospective study was undertaken to determine the survival of patients with stages I and II serous papillary adenocarcinoma of the endometrium. Twenty-eight patients were evaluable. The patients were treated by a variety of methods that included irradiation only, surgery only, combined irradiation and surgery, and chemotherapy. Eighteen patients had stage I disease and 10 patients had stage II disease. The 2-year survival rate was 16.6% for stage I patients and 40% for stage II patients. The overall 2-year survival rate was 28% for both groups of patients.     

食管原发性恶性黑色素瘤5例临床病理学观察

目的 观察食管原发性恶性黑色素瘤(primary malignant melanoma of esophagus,PMME)的影像学、病理组织学和免疫表型特征,探讨其临床病理学特征、诊断、鉴别诊断及治疗.方法 对5例PMME行HE及免疫组化染色,并结合相关文献对其临床表现、影像学、组织学形态、免疫表型、治疗和预后进行观察分析.结果 5例患者均为老年男性,平均年龄63.4岁,临床均表现为进食不畅,症状呈进行性加重.肿瘤细胞呈巢片状或条索状排列,细胞圆形或多角形,胞质丰富红染,胞质内见黑色素颗粒,细胞核大小不一,核居中或偏位,核仁明显,病理性核分裂象易见.免疫表型:瘤细胞弥漫表达HMB-45、Melan-A、S-100,CK阴性,Ki-67增殖指数40％～ 45％.结论 PMME非常罕见,恶性程度高,预后差.免疫组化染色有助于其诊断,需与低分化癌、食管癌肉瘤、食管淋巴瘤、神经内分泌癌、食管平滑肌瘤等进行鉴别.     

Prognostic factors in cutaneous malignant melanoma. A comparative study of long term and short term survivors

The clinical presentation and histologic characteristics of primary melanomas of a consecutive series of 100 short term (fatal within five years) and 100 long term survivors (disease-free for ten years or longer) were studied. The clinical parameters analyzed included the history of pre-existent mole, duration of changes before diagnosis, site, elevation, ulceration, extent of pigmentation, and satellitosis around the primary lesion. Study of histologic features included analysis of exact measurements of the primary melanoma, depth of dermal invasion, tumor cell morphology, mitotic rate, intracellular pigmentation, presence or absence of giant tumor cells, blood vessel or lymphatic invasion, lateral junctional activity, and presence and extent of lymphoid response to the primary lesion.Statistically significant differences were found between the long term and short term survivors with respect to several variables. It is one of the conclusions of this study that an elective node dissection would seem to be indicated in all patients with stage I melanoma who present with poor prognostic signs, that is, patients who belong to any combination of the following categories: male, primary lesions>1 cm., which has ulcerated, with a deeper level of dermal penetration, with dermal lymphatic or blood vessel invasion, and a lack of lymphoid reaction around the primary lesion.