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.     

5例食管原发性恶性黑色素瘤临床病理分析

目的:分析食管原发性恶性黑色素瘤(primary malignant melanoma of the esophagus,PMME)的病理诊断特点、鉴别诊断、生物学行为及预后.方法:收集安阳市肿瘤医院5例PMME,对其进行光镜观察、免疫组织化学染色、临床病理分析并进行随访.结果:PMME多见于中老年人,常发生于食管中段,大体呈蕈伞型.光镜下瘤细胞异型性明显,呈梭形、卵圆形或不规则形,以梭形细胞为主.肿瘤细胞胞核体积大,核仁清晰、染色质丰富.瘤细胞形态多样且无色素易误诊为分化差的鳞状细胞癌、肉瘤样癌、淋巴瘤等.免疫组织化学结果肿瘤细胞显示vimentin,S-100,HMB-45和Melan-A阳性;不表达神经特异性烯醇化酶(neuron-specific enolase,NSE)、白细胞共同抗原(leukocyte common antigen,LCA)、细胞角蛋白(cytokeratin,CK)、嗜铬素蛋白-A(chromogranin proteins A,CgA)和突触素(syn).随瘤细胞浸润不同组织层次可伴有淋巴结转移.结论:PMME是一种罕见肿瘤,恶性度高、预后差.由于其症状与食管其它肿瘤相似,在活检或手术前很难确诊,对发生于中老年人的食管中段蕈伞型肿物应考虑原发性恶性黑色素瘤的可能.临床病理分析肿瘤大小、浸润层次、淋巴结转移及治疗方式可能影响预后.     

Two cases of early-stage esophageal malignant melanoma with long-term survival

Herein is described two patients with early-stage primary malignant melanoma of the esophagus with long-term survival who were treated with esophagectomy. Both tumors had similar pathological findings, and were mainly at the stage of radial growth phase. Widespread melanoses were present in the mucosa surrounding the tumors in both cases. The two patients recovered uneventfully after surgery and were in remission at follow up of 33 months and 53 months.     

Primary gastric malignant melanoma: challenge in preoperative diagnosis

Primary gastric melanoma is an extremely rare clinical entity. The clinical manifestation is not specific and usually similar with other common malignancies at this site, such as gastric cancer and lymphoma. And there are no specific radiological features either. Preoperative diagnosis via biopsy is usually difficult, since melanoma pigment could be absent in the biopsy tissue. Here, we report a case of a 50-year-old woman with a mass in the stomach found by gastroscopy. Biopsy was taken twice preoperatively under gastroscope and it was diagnosed as gastric carcinoma and neuroendocrine tumor respectively. Radical surgery was performed with gastrectomy and D2 lymph node dissection. Postoperative pathological examination finally made a definite diagnosis of gastric melanoma by immunohistochemistry. We summarize the reasons for preoperative misdiagnosis and discuss the difficulty in diagnosing gastric melanoma according to literature.     

Cutaneous malignant melanoma in teenagers

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.     

Subungual malignant melanoma: clinicopathological features of 100 cases

From the files of the Scottish Melanoma Group, we have identified 100 cases of subungual malignant melanoma (melanoma arising in the nailbed), and this represents 2.8% of the total melanomas registered during the period 1979-1989. Almost equal numbers arose on the foot as on the hand, with the thumb and big toe as the commonest digit affected. More than 80% were greater than 1.5 mm, with the mean Breslow depth 4.7 mm, and 70% were Clark level IV or V. Approximately half of the cases were of acral lentiginous type. At 5-year follow-up (54 cases), 26 have died of melanoma, six have died of an unrelated disease, four are alive with recurrence and 18 are alive and well. Features related to clinical outcome at 3 years were Breslow depth, mitotic count and the presence of vascular invasion.     

Primary malignant melanoma of esophagus: a case report and review of literature

Primary malignant melanoma of esophagus is a rare but highly aggressive neoplasm, with an incidence less than 0.2% of all primary esophagus neoplasms. There are no clinical differences from other forms of esophagus cancer. Because initial symptoms are nonspecific, the patients are usually diagnosed at a late stage. The prognosis is poor, and curative effect seems disappointed. Several reports suggest that most of patients die from distant metastases, and the 5-year survival rate is approximately 4.2%. This case report includes a review of the surgical pathology, clinical features and treatment of primary malignant melanoma of esophagus. This case report presents a 56-year-old female with primary malignant melanoma of esophagus, treated by surgical resection. Till now, the patient is still alive for 5 months without any chemotherapy, radiotherapy and immunomodulatory therapy.     

Primary malignant melanoma of the rectum

The diagnosis of a primary rectal malignant melanoma has been the subject of considerable argument for many years, principally on the grounds that extension from a primary anal lesion was often impossible to exclude. This paper provides evidence that certain melanomas can be recognized as primary rectal tumours, not only from careful anatomical assessment of the site of the tumour, but also by showing that they arise on a background of benign melanocytic proliferation in the rectal mucosa. The clinical presentation of these lesions, their possible mechanism of origin and their treatment is discussed.     

237例恶性黑色素瘤临床病理分析

目的:探讨237例恶性黑色素瘤(malignant melanoma,MM)的临床病理特点.方法:收集237例不同部位MM病例,复习其临床资料、HE形态,其中128例行免疫组织化学检测.结果:本组109例(45.99％,109/237)根据病史、发病部位、HE形态直接诊断;其余128例(54.01％,128/237)由于形态不典型、黑色素稀少或无色素,做免疫组织化学确诊,其中HMB45阳性率79％(101/128)、melan-A阳性率81％(104/128)、S-100阳性率90％(115/128).结论:MM的病理形态多样,免疫组织化学检测有助于诊断,其发病机制及临床治疗有待进一步探讨.     

Morphological and immunophenotypic variations in malignant melanoma

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet-ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi- or multi-nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro-/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB-45, Melan-A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.     

Cytodiagnosis of amelanotic metastatic malignant melanoma: An immunocytochemical study

Malignant melanomas are known to present diverse patterns and this can result in considerable difficulties for an interpretation of malignancy type from cytohistologic material. Such difficulties are further compounded, if melanin pigment cannot be demonstrated by conventional histochemical stains; unfortunately many cases do exhibit this feature, especially in its metastases. This study was designed to review cases of amelanotic metastatic malignant melanomas in a variety of cytologic samples which were received from 40 patients with a known history of malignant melanoma. Cytomorphologically, the cases were classified as classical, carcinoma-like, spindle cell type, lymphoma-like, and undifferentiated type (Table I). While in 36 of the cases, the diagnosis of metastases from a melanoma was confirmed based on an immunopositivity to a variety of melanoma markers (Table III), in four of the cases, the immunostaining indicated metastases from another primary source, which was subsequently found. Based on our study, we are of the opinion that an immunologic characterization is useful to conclusively diagnose the majority of cases of metastatic amelanotic malignant melanomas. Furthermore, we feel that a reliance on a single melanoma marker is not justified, and a panel of antibodies should be used to distinguish a metastatic amelanotic malignant melanoma from other metastatic neoplasms. Diagn. Cytopathol. 16:238–241, 1997. © 1997 Wiley-Liss, Inc.     

Verrucous naevoid and keratotic malignant melanoma: a clinico-pathological study of 20 cases

Verrucous naevoid malignant melanoma is a recently described variant of malignant melanoma that may be confused both clinically and histologically with benign lesions. This study reports the clinical and pathological features of 20 such cases. These constituted 3.2% of all melanomas diagnosed in the Department of Pathology, Aberdeen University, in the period 1970-1991. They occurred more often on the back and limbs of male patients with a mean age of 57 years. Clinical diagnosis of benign lesions (warty naevi, papillomas, seborrhoeic keratosis and cysts) were made in over 50% of the cases. Eight patients had metastases, seven of whom died of their disease. Microscopically, these lesions exhibited a spectrum of naevoid features such as symmetry, exophytic and papilliferous growth pattern, hyperkeratosis and pseudo-epitheliomatous hyperplasia. The majority, however, showed lateral intra-epidermal spread and were composed of large epithelioid cells exhibiting various degrees of cellular pleomorphism. Histological classification was difficult, as more than 50% of the cases were initially labelled unclassifiable. The marked papilliferous architecture of these lesions made assessment of Breslow depth and Clark levels difficult. Initially, 10% of the cases were histologically diagnosed as benign. It is therefore important for surgical pathologists to recognize this unusual variant of malignant melanoma, as it may be confused both clinically and pathologically with benign lesions.     

Immunohistochemically demonstrated metallothionein expression in malignant melanoma

Metallothioneins are ubiquitous proteins with a high affinity for heavy metal ions, e.g. zinc, copper and cadmium. Experimentally, metallothionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiation therapy. Using a monoclonal antibody (E9) to metallothionein we investigated immunoreactive expression in routinely fixed and paraffin-embedded tissue from 63 cases of malignant melanoma and 13 secondary deposits. Whereas a variety of cells in normal skin showed metallothionein expression, all forms of benign naevi studied were uniformly negative. In contrast 13/30 'thin' (≤1.5 mm; 0.7 ± 0.4). 25 29 'thick' malignant melanoma (> 1.5 mm; 5.5 ± 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick melanoma with metallothionein expression died during a mean observation period of 6.4 ± 1.8 and 3.6 ± 2.5 years, respectively, their survival distribution function analyses giving statistically significant results for both the vertical tumour thickness ( P < 0.0001) and metallothionein expression ( P < 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallothionein expression in malignant melanoma is significantly associated with progressive disease and might therefore be a useful prognostic indicator.     

Intranasal malignant melanoma arising in an inverted papilloma

A case of intranasal malignant melanoma arising in the epithelium of an inverted papilloma is described. The use of immunohistochemistry to delineate the in situ component of the malignant tumour is illustrated and the characteristic features of malignant melanomas at this site discussed.     

Immunotherapy of malignant melanoma with tumor lysate-pulsed autologous monocyte-derived dendritic cells

Purpose

Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea.

Materials and Methods

Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time.

Results

Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients.

Conclusion

In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.     

A case of metastatic malignant melanoma masquerading as disseminated mammary carcinoma

A 42-year-old woman presented with widespread secondaries and a mammary mass. A provisional diagnosis of metastatic breast carcinoma was made. Histological evaluation of the mammary tumour including immunohistochemical studies suggested the diagnosis of metastatic malignant melanoma, which was later confirmed.     

Is poor prognosis really related to HLA-DR expression by malignant melanoma cells?

HLA-DR expression was examined in 50 consecutive primary cutaneous malignant melanomas with a Breslow depth greater than 2 mm using two well-characterized monoclonal antibodies which detect fixation-resistant epitopes. In 31 of these cases (62%) a subpopulation of tumour cells was reactive, although there was considerable heterogeneity. Positive labelling did not correlate with depth but was associated with a reduced likelihood of developing early metastatic disease and a tendency for better overall survival, particularly in male patients. These findings contrast with earlier studies using cryostat sections and one study on paraffin-embedded tissue in which HLA-DR expression was shown to be a poor prognostic factor, but are consistent with the findings in other malignant tumours studied. The significance of HLA-DR expression as a marker of prognosis may depend on the type of tissue preparation, the sensitivity of the immunocytochemical techniques used and the method of assessment.