宫颈微偏腺癌的临床病理分析

目的探讨宫颈微偏腺癌的临床及病理形态特征、诊断要点及有辅助诊断意义的免疫组织化学指标,以提高及时诊断的准确性.方法收集13例诊断为宫颈微偏腺癌的临床病理资料,分析其特征,5例作免疫组织化学(LDP法)和组织化学(Foot)染色(以正常宫颈腺体为对照);随访其疗效.结果临床主要表现为水样白带,宫颈肥大,增粗变硬和糜烂,宫旁韧带增厚或硬.病理特征为腺体增生,有轻度异型性,有向间质浸润的反应,或浸至宫颈间质层.癌胚抗原3+,Ki-67+～3+,p53蛋白+～3+,AB/PAS+或2+,Foot染色腺体基底膜部分缺失.结论诊断宫颈微偏腺癌应结合临床表现,指出宫颈腺体有无不典型增生,并深取组织(>5 mm)或高频电力锥切宫颈活检,可及时诊断,防止漏诊.     

A clinicopathological and immunohistochemical study of minimal deviation adenocarcinoma of the uterine cervix

Objective

To investigate the clinical, pathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of the uterine cervix by conducting a retrospective study of 25 cases consecutively treated in three institutes over a 10 years period.

Methods

Of 25 cases with MDA, clinical features were retrospectively reviewed, gross and micro appearances of surgical specimens of 17 operative cases were observed. Ki67, SMA, p53, PCNA, Vimentin, CEA, ER, CA125 and PR were detected on tissues from MDA and 50 cases common adenocarcinomas of the uterine cervix (AUCs) (differentiation rank: high 16, moderate 20, low 14). Their expressions were assessed in paraffin sections using the immunohistochemistry method.

Results

MDA accounted for only 1.2% of adenocarcinomas of the uterine cervix. The main clinical manifestations were vaginal profuse, watery or mucoid discharge and irregular bleeding. Signs were cervical hypertrophy or thickening. The gross appearance showed many similarities with common AUCs. Immunohistochemical results: the positive rates for p53 and Ki67 in >50% of the cell nuclei (Ki67/50⁺) were 88% and 64% in MDA respectively, significantly higher than common AUCs (38%, 18%, P < 0.01), CA 125 was 18% in MDA, clearly lower than common AUCs (58%, P < 0.01). There was no difference between MDA and common AUCs for CEA, PR, Vimentin, ER, PCNA and SMA (P > 0.05). No significant difference was noticed among the high, moderate and low differentiation groups in common AUCs (P > 0.05).

Conclusions

For early stage diagnoses, MDA should be considered when cervical hypertrophy is present in patients complaining of a vaginal profuse watery or mucoid discharge and irregular bleeding. Positive immunohistochemical staining for p53, Ki67/50⁺ and negative for CA125 can assist diagnosis and discrimination.     

Exfoliative cytology of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix

Cervical scraping smears from two cases of histologically confirmed adenoma malignum of the uterine cervix were reviewed. In one case, several irregular sheets of benign-appearing glandular cells with slightly enlarged nuclei, conspicuous nucleoli, and clear cytoplasm were found. In the other case, in addition to sheets of benign-appearing glandular cells, there were clustered malignant glandular cells with prominent nucleoli. The sheets of benign-appearing glandular cells in both cases displayed wispy cytoplasmic extensions or “tails.” Cytologic differential diagnosis with other glandular lesions of the cervix such as clear cell carcinoma, microglandular hyperplasia, diffuse laminar glandular hyperplasia, tubal metaplasia, and well-differentiated invasive or in situ adenocarcinoma is briefly discussed. © 1995 Wiley-Liss, Inc.     

Well-differentiated adenocarcinoma of the gallbladder mimicking minimal deviation adenocarcinoma of the cervix

We report a case of well-differentiated adenocarcinoma of the gallbladder, histologically mimicking minimal deviation adenocarcinoma (MDA) of the cervix. A 71-year-old Japanese male underwent cholecystectomy because of the suggestion of gallbladder carcinoma. The resected gallbladder showed a localized thickening of the gallbladder wall with a polypoid lesion measuring 12x7 mm in diameter. Microscopically, the polypoid lesion proved to be a well-differentiated adenocarcinoma composed of columnar cells with a clear cytoplasm. In the thickened gallbladder wall, well-formed glands were extensively distributed; they were surrounded by a slightly desmoplastic reaction instead of lamina propria, or were directly in contact with smooth muscle cells. The diagnostic criteria for cervical MDA may be useful in distinguishing well-differentiated adenocarcinoma of the gallbladder from benign conditions, such as Rokitansky-Aschoff sinus and adenomyomatosis. It is remarkable that the tumor cells of the present case expressed gastric type mucin which is characteristic of mucinous type cervical MDA.     

Interobserver variation in the diagnosis of adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix

To examine the interobserver agreement level of the histological diagnosis of adenoma malignum (ADM), 52 proliferative endocervical glandular lesions were evaluated independently by four observers (A to D), each of whom is in charge of gynecological pathology at a different hospital. The correlation of diagnosis by each observer with patient outcome was also examined for 19 of these lesions. When the diagnoses were categorized into benign lesions including hyperplasias, ADM, and common types of adenocarcinoma, consistent diagnoses among all observers were achieved for only 12 lesions (23%), with a slight level of interobserver agreement (kappa=0.115). The points of disagreement were as follows: (i) whether proliferative endocervical glandular lesions preserving lobular structures were diagnosed as benign or as ADM; and (ii) whether proliferative endocervical glandular lesions with a discrete area of obvious adenocarcinoma were diagnosed as ADM or as common-type adenocarcinoma. The mortality rates of patients with ADM diagnosed by observers A, B, C, and D were 60% (3 of 5), 25% (3 of 12), 14% (1 of 7), and 13% (2 of 15), respectively. Therefore, ADM diagnosed by observers A and B was frequently lethal, whereas ADM diagnosed by observers C and D was mostly non-lethal and might contain benign lesions. The diagnosis of ADM covered various spectra of proliferative endocervical glandular lesions among the observers. Disagreement in the diagnosis was suggested to derive largely from the absence of consensus criteria for differential diagnosis among benign hyperplastic lesions, ADM, and common adenocarcinoma, and from differences in the observers' interpretations about cellular atypia and invasion.     

Mutations in the human LKB1/STK11 gene

The human LKB gene (official HUGO symbol, STK11) encodes a serine/threonine protein kinase that is defective in patients with Peutz-Jeghers syndrome (PJS). PJS is an autosomal dominantly inherited syndrome characterized by hamartomatous polyposis of the gastrointestinal tract and mucocutaneous pigmentation. To date, 145 different germline LKB1 mutations have been reported. The majority of the mutations lead to a truncated protein product. One mutational hotspot has been observed. A 1-bp deletion and a 1-bp insertion at the mononucleotide repeat (C6 repeat, c.837-c.842) between the codons 279-281 have been found in six and seven unrelated PJS families, respectively. However, these mutations account only for approximately 7% of all mutations identified in the PJS families (13/193). A review of the literature provides a total of 40 different somatic LKB1 mutations in 41 sporadic tumors and seven cancer cell lines. Mutations occur particularly in lung and colorectal cancer. Most of the somatic LKB1 mutations result in truncation of the protein. A mutational hotspot seems to be a C6 repeat accounting for 12.5% of all somatic mutations (6/48). These results are concordant with the germline mutation spectrum. However, the proportion of the missense mutations seems to be higher among the somatic mutations (45%) than among the germline mutations (21%), and only seven of the mutations are exactly the same in both of the mutation types.     

子宫颈微偏腺癌6例临床病理分析

目的探讨子宫颈微偏腺癌的形态学、组织化学及免疫表型特征。方法对6例子宫颈微偏腺癌组织学特征进行观察,并行黏液组化及免疫组化染色（S-P法）。结果6例均有子宫颈腺体显著增生,腺体腔缘面呈花边状、锯齿状或乳头状突入到腺管腔内,并有成角状外翻,腺体呈浸润性生长。黏液组织化学：AB（pH1．0、2．5）／PAS染色证实,腺体腔内为混合性黏液,主要含唾液酸黏液,硫酸黏液减少,中性黏液较多。免疫表型：CEA（5／6）阳性,CA125（6／6）阴性。vimentin、SMA浸润性腺体周围纤维母细胞／肌纤维母细胞（6／6）阳性。结论子宫颈微偏腺癌以其特殊的形态结构和细胞轻微的异型、AB／PAS阳性、CEA阳性及腺体周围反应性纤维母细胞／肌纤维母细胞增生为特征。     

Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal deviation adenocarcinoma of uterine cervix

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated tumor of uterine cervix, of which the confusing histopathology resembling some benign lesions usually makes difficulty for pathologic diagnosis. The expression of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is considered to be associated with the progression of the tumors. The purpose of this study is to detect the FOXP1 expression in MDA and evaluate its possible role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases of normal endocervical tissue were included in this study. All available clinical data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA), human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone receptor were performed on these cases. The nuclear/cytoplasmic expression of FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which showed statistical significance (P = .000). The cytoplasmic CEA expression was found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control cases (P = .081). No statistical difference was found between FOXP1 and CEA expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA. Neither estrogen receptor nor PR expression was found in MDA. The significant expression of FOXP1 in MDA may be helpful to some extent in the pathologic diagnosis of cervical MDA. A widened observation range and further researches are needed to elucidate the potential mechanism.     

Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA)

Lobular endocervical glandular hyperplasia (LEGH) is a benign proliferative disease of cervical glands. Although histological resemblance of minimal deviation adenocarcinoma (MDA) to LEGH and frequent association of LEGH with MDA have been reported, it still remains unclear whether LEGH is a precancerous lesion of MDA. The present study was undertaken to examine the pathogenetic relationship between LEGH and MDA using a clonality analysis and mutational analyses of the STK11 gene, of which mutations have been reported in MDA. Of nine cases of LEGH only, four were polyclonal and five were monoclonal in composition. Of six LEGH lesions associated with MDA or adenocarcinoma, two were polyclonal and four were monoclonal. In cases of MDA or adenocarcinoma coexisting with LEGH, the patterns of X chromosome inactivation in malignant lesions were identical to those in coexisting LEGH lesions. A mutation of STK11 was only identified in one MDA, but not in LEGH. These results indicate that a subset of LEGH may be a precursor to malignant tumors including MDA and that a mutation of STK11 may be involved in progression of LEGH to MDA.     

宫颈微偏腺癌六例伴五例卵巢转移的临床病理学分析

目的:探讨宫颈微偏腺癌（minimal deviation adenocarcinoma of cervix,MDA）伴卵巢转移临床病理特征。方法:收集四川省肿瘤医院2014年1月至2019年12月确诊MDA 6例伴卵巢转移5例,总结其临床病理特点及HER2表达状况,并结合文献复习。结果:6例患者年龄33~71岁,中位...     

粗针活检诊断子宫颈微偏腺癌4例及临床病理分析

目的 总结B超引导下子宫颈微偏腺癌(minimal deviation adenocarcinoma,MDA)的粗针穿刺活检组织病理学形态、免疫组化及组织化学染色、病理诊断和鉴别诊断等要点,结合文献分析粗针穿刺活检方法用于临床早期诊断子宫颈MDA的优势及可行性.方法 对4例临床疑为MDA的患者,在B超引导下进行深部粗针穿刺活检,经常规HE染色、免疫组化及特殊染色后,镜下观察做出病理诊断,与该患者根治切除标本进行对比分析.结果 镜下见子宫颈深部穿刺标本的纤维和平滑肌组织中,散在分化较好的子宫颈型黏液性腺体,但腺体形态不规则,细胞轻至中度异型以及周围纤维组织增生性的间质反应,并且可见腺体邻近大血管;免疫组化染色腺上皮CEA阳性,AB/PAS特殊染色阳性.根治切除标本进一步明确了MDA的诊断,证实术前的子宫颈深部组织粗针穿刺活检获得的组织学证据,足以支持MDA的病理诊断.结论 MDA病变位置较深,间质浸润是明确诊断的最主要依据,粗针穿刺可做到子宫颈深部(深度>5 mm)活检,作为MDA早期诊断的一种方法具有一定的优势和可行性.     

Invasive adenocarcinoma and related tumors of the uterine cervix

Adenocarcinomas and related tumors now account for approximately 15% of carcinomas of the uterine cervix. In this review, the features of these neoplasms are reviewed with emphasis on their microscopic features, differential diagnosis, and subtypes about which there is new information such as adenoma malignum, and villoglandular, mesonephric, adenoid basal, and adenoid cystic carcinomas. These tumors may cause considerable diagnostic difficulty, sometimes being difficult to distinguish from nonneoplastic glandular proliferations. Their correct identification has major prognostic implications.     

Endometrioid adenocarcinoma of the uterus with a minimal deviation invasive pattern

AIMS: Minimal deviation adenocarcinoma of endometrioid type is a rare pathological entity. We describe a variant of typical endometrioid adenocarcinoma associated with minimal deviation adenocarcinoma of endometrioid type. METHODS AND RESULTS: One 'pilot' case of minimal deviation adenocarcinoma of endometrioid type associated with typical endometrioid adenocarcinoma was encountered at our institution in 2001. A second case of same type was received in consultation. We reviewed 168 consecutive hysterectomy specimens diagnosed with 'endometrioid adenocarcinoma' specifically to identify areas of minimal deviation adenocarcinoma of endometrioid type. Immunohistochemistry was done with the following antibodies: MIB1, p53, oestrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and vimentin (VIM). Four additional cases of minimal deviation adenocarcinoma of endometrioid type were identified. All six cases of minimal deviation adenocarcinoma of endometrioid type were associated with superficial endometrioid adenocarcinoma. In two cases with a large amount of minimal deviation adenocarcinoma of endometrioid type, the cervix was involved. The immunoprofile of two representative cases was ER+, PR+, CK7+, CK20-, CEA-, VIM+. MIB1 immunostaining of four cases revealed little proliferative activity of the minimal deviation adenocarcinoma of endometrioid type glandular cells (0-1%) compared with the associated 'typical' endometrioid adenocarcinoma (20-30%). The same four cases showed no p53 immunostaining in minimal deviation adenocarcinoma of endometrioid type compared with a range of positive staining in the associated endometrioid adenocarcinoma. CONCLUSIONS: Minimal deviation adenocarcinoma of endometrioid type more often develops as a result of differentiation from typical endometrioid adenocarcinoma than de novo. Due to its deceptively benign microscopic appearance, minimal deviation adenocarcinoma of endometrioid type may be overlooked and may lead to incorrect assessment of tumour depth and pathological stage. There was a tendency for tumour with a large amount of minimal deviation adenocarcinoma of endometrioid type to invade the cervix.     

Intranuclear cytoplasmic inclusion is a significant diagnostic feature for the differentiation of lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma of the cervix

Lobular endocervical glandular hyperplasia (LEGH) is a cervical lesion with pyloric gland metaplasia. Minimal deviation adenocarcinoma (MDA) is an extremely well differentiated form of endocervical adenocarcinoma (AC). To date, it is difficult to differentiate LEGH from MDA because they share similar clinical, radiological, and immunohistochemical features. Furthermore, the cytological features of LEGH and MDA have not been well defined. In the present study, we describe the cytological features of LEGH and MDA. We reviewed 24 cases of LEGH (18 pure and six mixed forms) and four MDA cases of the cervix. A total of 40 cytologic smears from 28 patients were reviewed. Abundant yellow mucin was frequently present in both LEGH and MDA; however, an INCI was found in 22 of the 24 LEGH cases and it was not found in either MDA or adenocarcinoma cells associated with LEGH. Neither cell atypia nor architectural distortion was observed in LEGH. In MDA, slight cellular atypia, three dimensional, irregular cell clustering, and prominent nucleoli were observed. The presence of an INCI is a good parameter for the diagnosis of LEGH. Cytology is an effective aid in the differentiation of LEGH from MDA.     

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix

Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival.     

子宫颈腺癌与子宫内膜腺癌的组化及免疫组化观察

目的：探讨组化染色及免疫组化在宫颈腺癌与宫内膜腺癌诊断价值及临床意义。方法：采用组化染色及免疫组化Ｓ－Ｐ方法对宫颈腺癌及宫内膜腺癌的粘蛋白含量、分布及免疫组化阳性物的表达进行观察。结果：宫颈腺癌以含丰富的唾液酸粘蛋白为主，而子宫内膜腺癌以硫酸粘蛋白为主。波形蛋白（ｖｉｍｅｎｔｉｎ）在宫内膜腺癌阳性表达率６８．９％，而宫颈腺癌大多呈阴性表达，雌激素受体（ＥＲ）表达在宫内膜腺癌达６０．９％，而宫颈腺癌仅１９．６％，两者均差异有显著性（Ｐ＜０．０５）。而抑癌基因ｐ５３和癌基因ｃ－ｅｒｂＢ－２阳性率与癌肿的分级和预后有关。结果：粘蛋白组化染色及ｖｉｍｅｎｔｉｎ可帮助鉴别诊断宫颈腺癌及宫内膜腺癌，而ＥＲ、ｐ５３、ｃ－ｅｒｂＢ－２对病人的预后有一定意义     

Mixed papillary adenocarcinoma and transitional cell carcinoma of the uterine cervix

A mixed papillary adenocarcinoma and transitional cell carcinoma (MAcTcc) was discovered in the uterine cervix of a 38-year-old woman. A condylomatous papillary lesion was found in the uterine cervix during a colposcopic study and histopathological examination showed that the tumor was composed of two different neoplastic subtypes. One was an adenocarcinoma (AC) component showing papillary and tubular structure with endocervical and intestinal differentiation; the other was a transitional cell carcinoma (TCC) component showing papillary excrescence mimicking papillary TCC of urothelial origin. To characterize the tumor, an immunohistochemical study of cytokeratins (CK) was performed. The AC component showed immunoreactivities similar to conventional adenocarcinomas: positive immunoreactivity of low-molecular-weight cytokeratins 7, 8 and 19, and negative immunoreactivity of CK20 and high-molecular-weight cytokeratin (34βE12). The lower epithelial layer of the TCC component showed different immunoreactivity, but the superficial epithelial layer had similar immunohistochemical findings to the AC component. These findings indicate that the TCC component had the cellular character of AC rather than that of TCC or squamous cell carcinomas. This is thought to be the first report of a MAcTcc of the uterine cervix.