40例原发性粘膜恶性黑色素瘤临床病理分析

目的：观察粘膜黑色素瘤的临床及病理形态学特性并探讨其组织发生，方法：对４０例粘膜黑色素瘤进行了光镜观察，并对部分病例作组化及免疫染色，结果：４０例粘膜恶黑中，发生于鼻腔１６例，肛管直肠８例，口腔７例，眼结膜４例，阴道２例，鼻咽部，宫颈及尿道各１例，发病年龄３３～７５岁（平均５７岁）镜下改变与皮肤黑色素瘤类似，免疫线化染色Ｓ－１００阳性率为９５％，ＨＭＢ４５为９０％，结论：粘膜黑色素瘤的临床病理特点     

Diagnostic lessons of mucosal melanoma with osteocartilaginous differentiation

Aims : To document the clinical, morphological and immunohistochemical features of two cases of primary mucosal melanoma with osteocartilaginous differentiation.  

Materials and methods

Two cases of mucosal melanoma with cartilage and bone formation are reported, one arising in the vagina of a 79-year-old woman and one in the oral cavity of a 67-year-old man. The vaginal melanoma exhibited only cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both bone and cartilage formation and was remarkable for its multifocality, long history not associated with metastases and its lengthy manifestation of dual morphologies: some of the tumours were typical in situ/invasive melanotic melanomas whilst the others were composed of amelanotic spindle and epithelioid cells with osteocartilaginous tissue. One of the lesions exhibited in situ and invasive melanoma with transition to an osteogenic tumour in places. The patient also developed non-osteogenic malignant melanomas in the nasal cavity and nasopharynx.  

Conclusions

Malignant melanomas showing foci of osteocartilaginous differentiation are extremely rare with only 18 cases reported. Primary mucosal malignant melanomas of vagina and oral cavity showing osteocartilaginous differentiation have not previously been documented. Primary vaginal melanoma with cartilaginous differentiation must be distinguished from primary malignant mixed Müllerian tumour whilst malignant change in a pleomorphic adenoma, sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are included in the differential diagnosis of primary oral mucosal melanomas with osteocartilaginous differentiation. In this context, immunohistochemistry using antibodies to cytokeratin, S100 protein and MIC2 is of value.     

Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

Optical coherence tomography (OCT) is a noninvasive imaging methodology that is able to image tissue to depths of over 1 mm. Many epithelial conditions, such as melanoma and oral cancers, require an invasive biopsy for diagnosis. A noninvasive, real-time, point of care method of imaging depth-resolved epithelial structure could greatly improve early diagnosis and long-term monitoring in patients. Here, we have used tissue-engineered (TE) models of normal skin and oral mucosa to generate models of melanoma and oral cancer. We have used these to determine the ability of OCT to image epithelial differences in vitro. We report that while in vivo OCT gives reasonable depth information for both skin and oral mucosa, in vitro the information provided is less detailed but still useful. OCT can provide reassurance on the development of TE models of skin and oral mucosa as they develop in vitro. OCT was able to detect the gross alteration in the epithelium of skin and mucosal models generated with malignant cell lines but was less able to detect alteration in the epithelium of TE models that mimicked oral dysplasia or, in models where tumor cells had penetrated into the dermis.     

Metastatic tumors in oral mucosa and jawbones: Unusual primary origins and unusual oral locations

AimTo perform clinico-pathological characterization of a large series of oral metastases, collected from 3 main medical centers in Israel and compare findings to data on frequency of primary cancer types in the population.MaterialsPathology archives were searched for cases of metastatic tumors to the oral soft tissues and jawbones, 1990 – 2016. Metastases to the skin of face or to major salivary glands have been excluded. Demographic data and histopathological features were analyzed.ResultsStudy population included 60 patients, 35 females and 25 males (ratio of 1.4:1). The age range was 17–87 years, mean 67.7 + 14.36 years. Only 3 (5%) patients were under 40 years, the remaining clustered predominantly in the 60–80 year age group. The mean age of females (59 + 13.84) was significantly lower than that of males (67.44 + 14) (p = 0.03). There was an almost equal distribution between the oral soft tissue and the jawbones (48.3% and 51.7%, respectively). The five most common organs from which metastases were distributed to the oral cavity and jawbones combined were kidney (20%), breast (15%), cutaneous (predominately melanoma, 13%), lung (11.7%) and soft tissue-sarcomas (8.3%). For comparison, Israel National Cancer Registry 2013 reported that the most frequent malignancies were breast (25.8%), colorectal cancer (16.3%), lung (12%) and prostate (10%). Malignant melanoma was 6th (5.4%), kidney malignancy was only 9th in frequency (4.2%). Although the gingiva and jawbones were the most frequent locations, some cases presented in unusual locations, (mandibular vestibule, lower lip, posterior dorsal tongue), without any specific clinical feature to suggest metastasis.ConclusionsThe most frequent primary origins for oral metastasis do not correspond to the relative frequency of the primary tumors in the population, indicating that metastatic spread is not a random process. Although the majority of metastasis involves the gingiva and jawbones, any other oral mucosal location might be involved. Thus, in adult/older patients, metastasis from a distant site should be included in the differential diagnosis of oral masses at any oral location, whether the existence of a primary tumor is reported or not.     

Primary malignant melanoma of the esophagus: a clinicopathologic study of a case with comprehensive literature review

Primary malignant melanoma originating in the digestive tract is particularly rare, mainly affecting the anorectum and oral cavity. Primary malignant melanoma of the esophagus has been the subject mostly of case reports. This tumor has a dismal prognosis with a frequency estimated to be approximately 0.1% to 0.2% of all esophageal malignancies. According to the review by Volpin et al of November 2002, 238 cases of primary malignant melanoma of the esophagus have been published up to early 2001. We present an additional case of primary malignant melanoma of the esophagus of the amelanotic variant in a 69-year-old man. The patient was preoperatively investigated by esophageal endoscopy and endoscopic ultrasound. The surgically resected tumor specimen was examined histologically and supplemented by immunohistochemical and ultrastructural analysis. Intra-abdominal relapse occurred after 8 months at the site of surgery, necessitating repeat resection. The patient died of advanced intra-abdominal disease 14 months after the primary diagnosis. A comprehensive computerized (PubMed/Medline) review of the world literature was also carried out and 99 additional cases (after the review by Volpin et al) were found, 9 of them from the 1990s which escaped previous tabulations, and 90 from the years 2000 to 2010, amounting to a grand total of 337 ever published.     

Epidemiological aspects of melanoma: a review

The principal factors in the incidence of melanoma are racial susceptibility, skin pigmentation and latitude of domicile. Celts, Norwegians and Swedes all have higher incidences of melanoma than people of similar skin colour living in the same latitude. Skin pigment protects but the pigmented races have higher incidences of melanoma in the less pigmented regions such as the sole of the foot and the various squamous mucosae. There is a direct relationship with latitude of residence and its duration, melanoma incidence being higher with proximity to the equator. Apart from these racial and environmental factors, there seem also to be endogenous factors responsible for familial melanoma and for the development of melanoma in young persons. Multiplicity of primary growths is a feature in familial cases.     

Mucosal malignant melanoma – a clinical,oncological, pathological and genetic survey

Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour‐specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found – except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5‐year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).     

EBV-associated ulceration in an immunocompromised patient

Epstein Barr virus-positive mucocutaneous ulceration (EBVMCU) is an uncommon entity first described in 2010. This lymphoproliferative disorder was first described in immunocompromised patients presenting with well-defined ulceration involving the oral cavity, skin and gastrointestinal tract. The first case series suggested that EBVMCU is generally self-limiting and likely to resolve without treatment. However, since then, additional cases reported have described a more heterogeneous course. Many people are infected with Epstein Barr virus (EBV) at a young age and this usually has a self-limiting course. However, immunosuppression due to any cause, including age-related immunosenescene may facilitate a wide spectrum of EBV-related lymphoid hyperplasia and lymphoma. We describe a case of oral presentation of EBVMU in a patient on long term immunosuppressants.     

Mucocutaneous angiomyolipoma. A report of 2 cases arising in the nasal cavity.

OBJECTIVE: Angiomyolipoma (AML) is a distinctive tumor that usually occurs in the kidney and rarely in the liver. Angiomyolipoma of other sites is extremely rare, and, to our knowledge, only 2 cases have been described in the nasal cavity. We present 2 additional cases of AML of the nasal cavity and discuss the difference between them and renal AML. CASE REPORTS AND PATHOLOGIC FINDINGS: Two tumors in a 66-year-old man and an 88-year-old woman without tuberous sclerosis are described. They showed 20-mm, well-circumscribed, polypoid shapes. Histologically, they were composed of mature smooth muscle cells, fat cells, and various-sized blood vessels. In addition, aggregated small lymphocytes were noted. Neither epithelioid smooth muscle cells nor HMB45 immunoreactivity was seen in either case. CONCLUSIONS: The clinicopathologic features of AML of the nasal cavity are distinct from renal and hepatic AML and are common to those of AML arising in the skin and oral and pharyngeal mucosa. The term mucocutaneous angiomyolipoma is thought to be appropriate to express these characteristic tumors.     

Molecular and ultrastructural analysis of a multiphasic oral malignant melanoma

Melanomas of the oral cavity are extremely rare. Their rarity and their independence on exposure to UV radiation make them particularly interesting. The authors analyzed an oral multiphasic melanoma composed by a nodular nonpigmented ulcerated central region, a nodular ulcerated pigmented area, a pigmented nonulcerated region, and an area similar to a dysplastic nevus. They determined the expression of some genes involved in the differentiation and cellular transformation in morphologically different regions of melanoma. All these areas were also analyzed by electron microscopy. The various regions composing the melanoma expressed genes involved in melanogenesis and melanoma progression in a different manner. Electron microscopy observation of ultrathin sections of each region evidenced ultrastructural differences, being the cellular architecture more compromised in the most aggressive parts of the neoplasm. This pilot study identified morphological, molecular, and ultrastructural differences that characterize each region of the multiphasic melanoma.     

Primary Malignant Melanoma of Pleura: A Case Report and Literature Review

Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under‐reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648–652. © 2016 Wiley Periodicals, Inc.     

Histological changes in radial forearm skin flaps in the oral cavity

We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The "changed" flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy.     

Malignant melanoma in the oral region: ultrastructural and immunohistochemical studies

Malignant melanoma in the oral region is reviewed in its clinicopathological aspects. Clinically the melanomas were classified into five types; however, there were no histopathological differences according to these clinical types. Electron microscopic observation of the melanomas and primary culture cells derived from oral malignant melanoma revealed that, in patients whose prognoses were relatively good, many mature-stage melanosomes were found. Immunohistologically, there was a positive reaction for transferrin receptor and the expression of pRb2/p130 was found in only 2 of 13 patients, who are still alive after periods of over 14 years. The radiosensitivity of a cell line derived from human oral malignant melanoma was greater than that in cell lines derived from human cutaneous melanoma and with radiation, the number of melanosomes increased. There are very few clinical cases of oral malignant melanoma and very few cell lines derived from oral malignant melanoma, and so findings in these patients and these cell lines should be accumulated in order to clarify the biological behavior of oral malignant melanoma.     

Histochemical determination of copper, zinc, and iron in some benign and malignant tissues

Histochemical tests for copper, iron, and zinc revealed their presence in the stratum germinativum of normal skin and skin from which an early melanoma and basal cell and squamous cell carcinomas originated. However, only copper was seen in invasive cells of basal and squamous cell carcinomas originating from skin. The normal oral mucous membrane was free of copper, iron, and zinc, but cells of invasive squamous carcinoma originating from the oral mucous membrane contained copper. The fluorescent brightening agent, applied as a counterstain, aided in the location of the specimen.     

Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2 cases

Two cases of malignant melanoma are reported in adults exhibiting rhabdomyoblastic differentiation to alert pathologists to this rare variant of malignant melanoma. One of the cases presented as a metastasis in a submandibular lymph node, and the other was a primary skin melanoma. There are only a few published reports on melanocytic tumors with rhabdomyoblastic differentiation, mainly occurring in giant congenital nevi. Both cases reported here were confirmed by immunohistochemistry. Both cases were also studied by electron microscopy, and one showed distinctive ultrastructural features of striated muscle.     

Papillary formations in metastatic melanoma

Cytomorphologic features of melanoma can be extremely variable, in that they can mimic other poorly differentiated neoplasms. Ten cases of metastatic melanoma with distinct, cohesive, papillary tissue fragments observed in fine-needle aspiration (FNA) specimens are reported. These papillary fragments exhibited a central fibrovascular core with attached tumor cells, in a background of single scattered malignant cells, macrophages, and focal necrosis. The aspiration sites included regional or distant palpable lymph nodes, pancreas, bone, and skin. Nine cases had a histologic diagnosis of primary cutaneous melanoma, and in one case the primary skin tumor was detected after the diagnosis was established by FNA of the metastasis. Immunohistochemical studies (S-100 protein, HMB-45 antigen, and factor VIII) were performed in four cases, and electron microscopy in one, confirming the diagnosis of melanoma. An awareness of this cytomorphologic variation of papillary formations in cytology preparations from metastatic melanoma is important and can prevent potential inaccurate interpretation.     

Cancers of the upper aerodigestive tract in Korea

Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all malignancies. Since the majority of cases are squamous cell carcinomas which are related with epidemiologic factors, a different pattern of UADT cancer might be present between the Western and Asian populations. We performed a pathology based statistical study on UADT cancers in Korean patients. Cases from Korea Cancer Center Hospital, from January 1, 1988 through December 31, 1998, were subjected to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%, with squamous cell carcinoma as the major type (76.5%). The larynx was the most commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%), which showed the most diverse tumor entities. Korean patients with UADT cancers presented with a higher incidence of non-epidermoid malignancy including sarcoma (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of the sinonasal tract, compared with the Western patients.     

Verruca vulgaris of the larynx. Demonstration of human papillomavirus types 6/11 by in situ hybridization.

Verruca vulgaris of the larynx (VVL) is a distinctly uncommon lesion related to the human papillomavirus (HPV). The clinical and pathologic features of a case involving the true vocal cords of a 37-year-old woman are presented and compared with the seven cases previously reported in the English language literature. Papillomavirus capsid antigen was detected in the excised tissue on immunostaining, and viral particles were seen by electron microscopy. In situ hybridization with biotinylated DNA probes clearly demonstrated HPV types 6/11. To our knowledge, this is the first case of VVL in which the virus associated with VVL has been genotyped. The results were unexpected because verruca vulgaris of the skin, lips, and oral cavity is associated with HPV types 2 and 4. This implies that verruca vulgaris can be caused by HPV types other than 2 and 4. In addition, since HPV types 6 and 11 are also the same genotypes associated with multiple papillomatosis of the larynx, it further indicates that VVL is virologically more related to multiple papillomatosis of the larynx than to its counterpart on the skin, lips, and oral cavity. The clinical and pathologic features that distinguish VVL from other similar lesions of the larynx are also discussed.     

Histologic analysis of intraepidermal melanocytic proliferation in the peripheral area of superficially diffused melanoma

Histological analysis of intraepidermal melanocytic proliferation in the peripheral areas of superficial spreading melanoma. The intraepidermal melanocytic proliferation in the areas adjacent to the invasive component of 100 superficial spreading melanomas of the skin (levels III and IV) was studied. Three patterns were identified: 1) melanoma in situ type (MIS); 2) melanocytic dysplasia type (DYS); 3) normal skin or increased number of typical melanocytes (0). The different distribution of these patterns in the areas adjacent to the invasive melanoma led to a histological classification of the tumors into 4 topographical models. Two models showed MIS areas and contiguous normal skin (A1, A2); two models showed MIS areas adjacent to DYS areas, that in turn were contiguous to normal skin (B1, B2). In all cases, however, in centrifugal sense, more severe alterations preceded less severe ones. These observations suggest that superficial spreading melanoma grows horizontally by induction of neighbour cells (neoplastic recruitment). The neoplastic transformation seems to progress in two ways: directly to melanoma in situ or through an intermediate phase (melanocytic dysplasia).     

A case of amelanotic melanoma of the nasal cavity

A 68-year-old male visited Hospital A for treatment of epistaxis, his chief complaint. He was told that he had an easily-bleeding tumor in the nasal cavity. Based of biopsy, a diagnosis of amelanotic melanoma was made. Operation was performed for removal of the tumor. About 8 months after discharge, he visited Hospital B with complaints of lumbar pain and epistaxis. After biopsy at Hospital B, malignant lymphoma (diffuse large cell) was diagnosed, and the patient was referred to our hospital. On bone marrow puncture and biopsy, tumor cell infiltration was observed. Flow cytometric surface marker analysis revealed that these tumor cells were negative for CD45. Results of HE staining of the nasal cavity tumor were insufficient for diagnosis, and staining by immunohistochemistry was necessary to confirm the diagnosis. On immunohistochemical staining of the nasal cavity tumor tissue and bone marrow biopsy tissue, LCA, L26 and UCHL-1 were negative, and S-100 and HMB-45 positive. Recurrence of amelanotic melanoma accompanied by bone marrow infiltration was therefore diagnosed. The incidence of amelanotic melanoma with primary lesions in the nasal cavity is low. However, in making the diagnosis of a nasal cavity lesion, the possibility of such a melanoma should be kept in mind. In many cases, it is difficult to diagnose amelanotic melanoma with HE staining alone, and immunohistochemistry must be used.