鼻腔鼻窦鳞癌、癌前期病变与癌基因c-myc扩增的相关性研究

目的：为明确鼻腔鼻窦鳞癌、癌前期病变与癌基因ｃ－ｍｙｃ的关系，为鼻腔鼻窦鳞癌和癌前期病变的早期诊断和诊疗提供依据和方法。方法：利用分子生物学技术对４４例标本进行分子病因学研究，包括２４例鼻腔鼻窦鳞癌，１５例良性肿瘤和５例鼻腔正常组织。结果：２４例鼻腔鼻窦鳞癌ｃ－ｍｙｃ的扩增倍数为１０～４０倍，癌前期病变组ｃ－ｍｙｃ的扩增倍数为５～１０倍，良性肿瘤及鼻腔正常组织中ｃ－ｍｙｃ的扩增倍数为５倍以下。结论：ｃ－ｍｙｃ的扩增水平与鼻腔鼻窦鳞癌的发生有关，与癌前期病变转化为恶性肿瘤有关。因而，ｃ－ｍｙｃ的水平可能作为临床鼻腔鼻窦鳞癌的分子水平诊断和检测鼻腔内翻性乳头状瘤是否有恶变倾向的一种参考指标。     

转移性非透明细胞肾细胞癌的治疗进展

非透明细胞肾细胞癌(nccRCC)是一组异质性疾病,一旦出现转移,对传统的全身治疗耐药,预后差。近些年的研究表明血管内皮生长因子抑制剂、m TOR抑制剂、MET抑制剂、细胞毒药物和免疫节点抑制剂对nccRCC治疗有效。对这些治疗方法进行综述以期提高对每种亚型nccRCC的最优治疗策略的认识。     

Adenoid squamous cell carcinoma of the oral cavity

Because immunohistochemical features of adenoid squamous cell carcinoma (AdSCC) of the oral cavity is unclear, the author reports herein AdSCC in the gingival with an emphasis on immunohistochemical features. A 73-year-old woman presented with a left lower gingival tumor. The tumor was mildly elevated tumor measuring 1.5 x 1.5 x 0.5 cm. Dentist's diagnosis was granulation tissue, and a biopsy was taken. The biopsy showed proliferation of carcinoma cells arranged in cords, and squamous and tubular differentiations were noted in places. The biopsy diagnosis was adenosquamous carcinoma. Tumor excision with resection of mandibular bone was performed. The resected tissue showed a mixture and squamous cell carcinoma and tubular formation. Gradual merges between the two and acantholytic features of the squamous cell carcinoma element were seen. Both components were free from mucins. Both components were positive for pancytokeratins (AE1/3, CAM5.2) +++, cytokeratin (CK) 5/6 +, CK34βE12 ++, CK7 +, CK14 +++, CEA +, CA19-9 +, CA125 +, p53 +++, p63 +++, KIT + and MUC1 ++. Both components were negative for CK8, CK18, CK19, CK20, EMA, vimentin, TTF-1, desmin, myoglobin, S100 protein, melanosome, smooth muscle actin, CD34, CDX2, CD10, chromogranin, synaptophysin, NSE, CD56, lysozyme, CD68, MDM2, PDGFRA, MUC2, MUC5AC, and MUC6. Since both components were positive for squmaous cell carcinoma markers (CD5/6, CK34βE12, and p63) and adenocarcinoma markers (CEA, CA19-9, CA125, MUC1), this case of AdSCC appears an intermediate form between adenocarcinoma and squamous cell carcinoma. The margins were negative. No metastasis was found by imaging techniques. The patient is now free from tumor and is followed up carefully.     

A rare case of nasal Schneiderian (inverted) papilloma associated with basaloid squamous cell carcinoma

Sinonasal inverted papilloma (IP) is a benign, locally aggressive epithelial neoplasm. In less than 9% of cases it is associated with malignancies, typically conventional squamous cell carcinomas (SCC), while other histological variants have been less frequently reported. We describe the third case of basaloid squamous cell carcinoma (BSCC) arising in nasal IP.An 81-year-old female patient presented with a pinkish irregular lesion on the nasal septum. Biopsy was consistent with IP and carcinoma in situ. Two surgical procedures were needed to obtain radical excision. Histology on the surgical specimen revealed BSCC. Seven months after surgery, there was no evidence of disease recurrence.Although IP is more frequently associated with conventional SCC, other malignancies should be considered. The histological differential diagnosis should be supported by immunohistochemistry. The generally-recommended treatment for sinonasal BSCC is complete surgical resection, although this may be a problem in multifocal distributions, as in the present case.     

转移性肾癌免疫治疗研究进展

转移性肾癌对传统放、化疗均不敏感,目前尚缺乏有效的治疗手段.IL-2和IFN-α是目前研究较多的细胞因子制剂,但单独应用于转移性肾癌患者的治疗时效率低.近年来,随着分子免疫机制的研究进展,疫苗、过继免疫治疗的研究发展迅速,特别是树突状细胞疫苗(DC vaccine)和自体细胞因子诱导的杀伤细胞(CIK)的研究取得了很大的进展.     

Primary adenoid squamous cell carcinoma of the oral cavity

Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. An additional case of ASCC is reported here. The patient was a 64-year-old Japanese woman who requested examination of a reddish lesion on the left floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma. Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which was categorized as cT2cN0cm 0. Tumor resection was therefore performed. Histologically, most parts of the lesion were conventional squamous cell carcinoma in situ, but the invasive part consisted of ASCC with gland-like or reticular appearance. The latter part was negative for mucin staining. Immunohistochemically, this lesion was positive for pancytokeratin, high-molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was 50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings and a review of the literature indicate that a gland-like feature of ASCC is associated with the loss of cell adhesion in the center of the cancer nests, and it can be confirmed simply by mucin staining to be neither an adenosquamous carcinoma nor ductal involvement of conventional squamous cell carcinoma.     

Renal cell carcinoma arising in a long pre-existing angiomyolipoma

Angiomyolipoma (AML) is a mixed mesenchymal tumor belonging to the family of perivascular epithelioid cell tumors. Concurrent development of AML and adult renal cell carcinoma (RCC) is very rare. Herein is presented a unique case in which RCC arose within a previously detected AML tumor mass. A 40-year-old woman had been diagnosed with AML of the right kidney. Fifteen years later, during a regular radiographic examination, a new lesion was detected at the lower pole of the right kidney adjacent to the previously described AML. Because RCC was clinically suspected, the patient underwent right nephrectomy. Macroscopically, the tumor had a yellowish, transparent, fatty area and an opaque yellowish area with cystic features. Microscopically, the former tumor, consisting of an admixture of mature adipose tissue with smooth muscle and vascular tissue, was diagnosed as AML. The latter tumor was diagnosed as RCC (clear cell type). RCC was not completely enclosed within the AML, but overlapped it. No fibrous capsule was found between these tumors. Although this situation is very rare, from a clinical and pathological point of view it is important to consider the possibility that RCC might arise within AML. The relationship between the two lesions is discussed with a review of the literature.     

Epithelioid angiomatous nodule of the nasal cavity

Epithelioid angiomatous nodule (EAN) is a recently described cutaneous vascular lesion with epithelioid features. We report two additional cases occurring in an unusual location in the nasal cavity. The patients were two young adults (17 and 26 years) presenting with recurrent unilateral epistaxis. Computerized tomography scan and endoscopy revealed small tumors that had developed in the nasal septum and the turbinate, measuring 1 and 1.5 cm, respectively. Endoscopic resection was performed. No recurrence was observed in the follow-up. Pathological examination revealed a well-limited but unencapsulated nodule composed of large epithelioid cells with round nuclei. Some tumor cells contained intracytoplasmic vacuoles. Mitotic activity was low without necrotic areas. Tumor cells were strongly immunostained with antibodies to CD34 and CD31. The main differential diagnosis is an epithelioid hemangioma sharing many morphologic features with EAN. We report these cases to inform of a possibly unusual location of EAN.     

Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability

den Bakker M A, Willemsen S, Grünberg K, Noorduijn L A, van Oosterhout M F M, van Suylen R J, Timens W, Vrugt B, Wiersma‐van Tilburg A & Thunnissen F B J M
(2010) Histopathology 56, 356–363 Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. Methods and results: One hundred and seventy cases of SCLC, LCNEC and cases diagnosed as neuroendocrine lung carcinoma before LCNEC had been established as a diagnostic category were retrieved from the archives of the assessor’s institutes. A representative haematoxylin and eosin section from each case was selected for review. Batches of cases were circulated among nine pathologists with a special interest in pulmonary pathology. Participants were asked to classify the cases histologically according to the 2004 World Health Organization (WHO) criteria. The diagnoses were collected and κ values calculated. Unanimity of diagnosis was achieved for only 20 cases; a majority diagnosis was reached for 115 cases. In 35 cases no consensus diagnosis could be reached. There was striking variability amongst assessors in diagnosing SCLC and LCNEC. The overall level of agreement for all cases included in this study was fair (κ = 0.40). Conclusions: Using non‐preselected cases, the morphological WHO criteria for diagnosing SCLC and LCNEC leave room for subjective pathological interpretation, which results in imprecise categorization of SCLC and LCNEC cases.     

Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist

Intertumor heterogeneity, defined as the spectrum of morphological differences found in similar tumors in different patients, is a well‐known event for pathologists. However, recent molecular studies have pointed to intratumor heterogeneity as one of the most important issues in human neoplasia in the next years. Clear cell renal cell carcinoma is an example of an intrinsically heterogeneous neoplasm, and some of the most salient advances in the knowledge of intratumor heterogeneity have been developed on it. This review intends to analyze this phenomenon in this tumor from the practicing pathologist's point of view. A careful study of the surgical specimen and an exhaustive tumor sampling are mandatory to keep relevant information. Currently accepted protocols designed for renal tumor sampling may be insufficient. As a result, a different approach to tumor sampling is advisable to ascertain that intratumor heterogeneity, if present, will be well represented in the selected material.     

Malignant lymphomas of the nasal cavity and paranasal sinuses

Summary The incidence of malignant lymphomas in the nasal cavity and paranasal sinuses was found tobe 0.17% of all malignant lymphomas and 0.44% of all extranodal malignant lymphomas registered in the Kiel Lymph Node Registry from 1972 to 1987. Fifty-nine cases of malignant lymphoma presenting in the nasal cavity and paranasal sinuses were investigated with morphological and immunological methods. The median age of the patients was 64.5 years, with a female predominance (m:f=0.87:1). In the 59 cases a marked preponderance of B-cell lymphomas was found (centroblasticn=15, immunoblasticn=8, Burkitt's lymphoman=6, Immunocytoman=3, centrocyticn=1, centroblastic/centrocyticn=1, plasmacyticn=11); only a small number (n=5) was of T-cell lineage (pleomorphic types). Nine further cases could not be assigned with certainty to either the T or B cell system. Angiocentricity with infiltration and destruction of vessel walls by tumour cells was demonstrated only in the T-cell lymphomas; the B-cell lymphomas, in contrast, of ten surrounded and compressed blood vessels with intact endothelium. No similarity to malignant lymphomas of mucosa associated lymphoid tissue, such as those in the gastrointestinal tract, was detected.     

Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition

Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.     

Fine-needle aspiration diagnosis of metastatic urothelial carcinoma: a review

Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine-needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction.     

A rare Japanese case with a NUT midline carcinoma in the nasal cavity: A case report with immunohistochemical and genetic analyses

Background

NUT (nuclear protein in testis) midline carcinoma (NMC) is a recently described aggressive malignancy that is genetically defined by rearrangements of the NUT locus at 15q14. In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. Only 10 sinonasal NMCs have been documented, none of which were Japanese cases.

Case presentation

An 18-year-old woman was admitted because of a rapidly progressing tumor in the nasal cavity. A biopsy revealed an undifferentiated neoplasm without squamous differentiation. The tumor cells had round to oval nuclei with vesicular chromatin, prominent nucleoli, and scant cytoplasm. Immunohistochemical staining demonstrated a strong positivity for vimentin and NUT, with focal CD138 and only spotty EMA and cytokeratin AE1/AE3 staining. Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. Direct sequencing identified the in-frame fusion of exon11 of BRD4 with exon2 of NUT. The patient was transferred to another hospital for chemoradiotherapy.

Conclusion

We herein describe the first Japanese case with an NMC of the sinonasal cavity, providing detailed and unambiguous cyto- and molecular genetic information on BRD4-NUT-rearrangement. The accumulation of cases with well-documented genetic data should provide clues to the treatment of this tumor entity.     

Renal cell carcinoma in South Korea: a multicenter study

The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs.