Minimal Deviation Adenocarcinoma Research Articles

Minimal Deviation Adenocarcinoma Associated with High-Grade Squamous Cervical Intraepithelial Neoplasia

Minimal Deviation Adenocarcinoma Associated with High-Grade Squamous Cervical Intraepithelial Neoplasia

A case of gastric-type adenocarcinoma of the uterine cervix associated with lobular endocervical glandular hyperplasia: radiologic–pathologic correlation

Gastric-type adenocarcinoma (GAS) of the uterine cervix is a recently defined subtype of mucinous adenocarcinoma. GAS is proposed to include minimal deviation adenocarcinoma (MDA) as a very well-differentiated form and has been suggested to arise from lobular endocervical glandular hyperplasia (LEGH). We report the magnetic resonance imaging (MRI) findings of a GAS associated with LEGH. On MRI, the LEGH component was detected as multiple cystic lesions arranged in a "cosmos pattern", while the GAS was depicted as a predominantly solid lesion containing obvious adenocarcinoma and MDA components, which appeared as mass-like and infiltrative components, respectively. The GAS exhibited tiny cysts on three-dimensional T2-weighted images, high intensity on diffusion-weighted images mostly due to T2 shine-through effect according to apparent diffusion coefficient (ADC) map, and reticular enhancement on dynamic contrast-enhanced MRI, which reflected numerous dilated glandular structures of the tumor. Low ADC was only observed at the deepest invasion front of the obvious adenocarcinoma component. Our case suggests that the MRI features of GAS vary depending on the tumor's histological components, and it is important to be aware of these imaging features when evaluating LEGH on MRI.

Minimal deviation adenocarcinoma of the uterine cervix: A case report

Minimal deviation adenocarcinoma (MDA) of the uterine cervix is a rare disease. The rate of misdiagnosis is relatively high and there is no standard treatment. A 58-year-old woman presented with an abnormal Pap smear revealing atypical glandular cells and vaginal mucoid discharge. Cervical biopsy revealed cervicitis and an endometrium with atypical glands and increasing mitoses. A frozen section of curetted endometrial tissue revealed adenocarcinoma. Surgical staging with laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic lymph node dissection was then performed. However, uterine cervical MDA was confirmed by pathology and immunohistochemistry with carcinoembryonic antigen and vimentin. Because the staging surgery was inadequate (the parametrium was not radically resected), postoperative adjuvant therapy with concurrent chemoradiation was performed. The patient remained disease-free as of the last follow-up 6 months postoperatively. MDA is difficult to diagnose and depends on its clinical manifestations and pathologic features. Surgery with adjuvant chemoradiotherapy achieves good outcomes.

Minimal deviation mucinous adenocarcinoma of the uterine cervix that proved difficult to differentiate from endometrial cancer: A case report.

Minimal deviation adenocarcinoma (MDA), also known as adenoma malignum of the uterine cervix, accounts for only ~1% of uterine cervical adenocarcinomas. Adenoma malignum of the uterine cervix was initially described by Gusserow in 1870. Using magnetic resonance imaging (MRI), MDA appears as multilocular lesions with solid components that extend from the endocervical glands to the deep cervical stroma. Cytological evaluation and biopsies have low detection rates, therefore, it is difficult to diagnose MDA accurately prior to treatment. The current study describes a rare case of MDA that was difficult to differentiate from endometrial adenocarcinoma of the corpus uteri preoperatively, as the endometrial biopsy results suggested a well-differentiated endometrioid adenocarcinoma and MRI did not show typical images for MDA. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the diagnosis of endometrial cancer, and the mass was subsequently diagnosed as MDA of the uterine cervix by pathological examination of the hysterectomy specimen. Postoperatively, although two types of adjuvant chemotherapy were performed, the remaining tumor continued to grow, causing obstruction of the bilateral ureters and leading to bilateral hydronephrosis. The patient is currently alive with the disease 10 months following the surgery.

Pseudoneoplastic glandular lesions of the uterine cervix: a selective review.

Pseudoneoplastic glandular lesions of the cervix continue to be diagnostically challenging for the surgical pathologist. This review covers a select number of these lesions that may be misinterpreted as premalignant or malignant, with an emphasis on those about which Dr Scully has advanced our knowledge. The topics covered include microglandular hyperplasia, mesonephric hyperplasia, diffuse laminar endocervical glandular hyperplasia, lobular endocervical glandular hyperplasia, and endocervical adenomyoma. The first listed entity has a greater diversity of morphology than the name might imply including, but not limited to solid growth and prominent hyaline stroma. The second entity may be remarkably diffuse within the cervical wall and reasonably result in consideration of diagnoses such as minimal deviation adenocarcinoma (adenoma malignum), but has nonmucinous epithelium and bland cytology. The third entity, one of the least common of those considered, represents a peculiar form of reactive hyperplasia of the endocervical epithelium. The fourth entity is the one about which knowledge is still fast advancing. In pure form with no atypia it is almost certainly a clinically benign process, but a subset of cases show cytologic atypia and an occasional association with adenocarcinoma is seen. Finally, adenomyomas of the uterus in general have received much attention in recent years, mostly in the corpus, but the less common endocervical variant may be particularly problematic because mucinous epithelium in abundant myogenic stroma may be potentially confused with an infiltrating differentiated mucinous adenocarcinoma. Although immunohistochemistry may play a role on occasion in evaluating benign endocervical glandular proliferations the mainstay of their interpretation remains conventional morphologic analysis of routinely stained slides.

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.

Lobular Endocervical Glandular Hyperplasia Is a Neoplastic Entity With Frequent Activating GNAS Mutations

To clarify the significance of GNAS mutations in cervical tumorigenesis, we performed mutational analyses in a total of 154 lesions and in 22 normal tissues of the uterine cervix. Activating GNAS mutations were found in 8 of the 19 lobular endocervical glandular hyperplasias (LEGH; 42%) and 4 of the 79 endocervical-type mucinous adenocarcinomas (5%) but were never seen in the normal endocervical tissue, minimal deviation adenocarcinomas, endometrioid adenocarcinomas, or squamous cell carcinomas. We further examined the presence of human papillomavirus (HPV) DNA and p16 expression to probe the relationship between GNAS mutations and HPV infection in LEGHs and carcinomas. All the GNAS-mutated LEGHs were negative for HPV DNA and p16 expression, whereas all the GNAS-mutated adenocarcinomas were positive for HPV DNA and/or p16 expression, implicating GNAS mutations in the development of LEGH and a minor subset of HPV-related cervical adenocarcinomas. Additional mutational analyses of LEGH identified KRAS and STK11 mutations in 1 and 2 cases, respectively. The GNAS, KRAS, and STK11 mutations were mutually exclusive; thus, a total of 11 LEGHs (58%) had 1 of these genetic alterations. Although LEGH has been regarded as a metaplastic lesion, the frequent presence of genetic alterations suggests a neoplastic nature.

A Tumor of the Uterine Cervix with a Complex Histology in a Peutz–Jeghers Syndrome Patient with Genomic Deletion of the STK11 Exon 1 Region

Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma.

Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

Diagnostic challenges in minimal deviation adenocarcinoma of the uterine cervix: A report of two cases and review of the literature

Minimal deviation adenocarcinoma (MDA) of the uterine cervix, otherwise known as adenoma malignum, is a rare variant of cervical adenocarcinoma, which represents a diagnostic challenge in the field of gynecologic oncology, due to its benign-resembling histological characteristics. To achieve a better understanding of this disease, we present two cases of MDA: one case presented with profuse watery discharge and cervical enlargement, accompanied by retention cysts and hardening; the other presented with a history of myoma cervicis uteri. Both patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy and our follow-up indicated that the patients were still free of any disease. Subsequently, a literature review was performed and the results demonstrated that early diagnosis, clinical stage and surgical protocols are the main factors affecting the prognosis of MDA. Close follow-up of the cases may provide more information regarding this disease and the efficacy of the available therapeutic methods.

Endocervical Glandular Lesions Exhibiting Gastric Differentiation

A variety of benign and malignant endocervical glandular lesions exhibiting gastric differentiation has been described in the past decade that has resulted in the concept of an important category of cervical adenocarcinoma which is unrelated to human papillomavirus (HPV). Both minimal deviation adenocarcinoma (MDA), also known as adenoma malignum, and the benign lesion lobular endocervical glandular hyperplasia (LEGH), have been known for some time to exhibit a gastric phenotype and immunophenotype (HIK1083 and/or MUC6 positive). Accumulated evidence suggests that a subset of LEGH (atypical LEGH) exhibits a degree of cytologic and/or architectural atypia which, in some cases, may be associated with and be a precursor of adenocarcinomas exhibiting gastric differentiation, including MDA. Gastric-type adenocarcinoma (GAS), a recently described subtype of cervical adenocarcinoma, is an emerging clinicopathologic entity. These neoplasms exhibit a spectrum of differentiation, including MDA as its very well-differentiated form, are unrelated to HPV, and exhibit aggressive clinical behavior. It is proposed that a LEGH-GAS sequence exists and, from a practical point of view, the development of optimal biomarkers is awaited to assist in early detection of GAS and atypical LEGH, as current HPV-targeted screening generally does not detect these lesions and strategies employing HPV vaccination will not prevent their occurrence. Pathologists should be familiar with the morphologic spectrum of these benign, premalignant, and malignant cervical glandular lesions exhibiting gastric differentiation. They are occasionally associated with Peutz-Jeghers syndrome or are a component of "synchronous mucinous metaplasia and neoplasia of the female genital tract."

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.

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

ObjectiveTo 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 10years period. MethodsOf 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. ResultsMDA 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). ConclusionsFor 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.

Adenoma malignum of the uterine cervix: Imaging features with clinicopathologic correlation

Adenoma malignum, also known as minimal deviation adenocarcinoma, is a subtype of mucinous adenocarcinoma of the cervix. To evaluate the clinical, pathologic, and imaging features of the adenoma malignum of the uterine cervix. We retrospectively analyzed the CT and MRI findings in 13 patients: size, endoluminal fluid, appearance of the solid and cystic component, margin, enhancement, characteristics of locules of the cystic lesion, tumor spread, and associated ovarian lesion. Clinical and pathologic features were determined in 24 patients. The mean of the major tumor diameter was 4.1 cm (range, 2.2-6.5 cm). In the imaging features, 77% of 13 tumors demonstrated endoluminal fluid. All tumors showed enhancing solid components; 62% were multicystic and 38% had solid lesions. Most solid lesions exhibited an irregular margin (80%). The locules of the multicystic lesions tended to have smooth margins (75%), to have an average major diameter of ≤1 cm (88%), and to be 11-20 in number (75%). The solid lesions were associated with invasion and metastases (60%). Clinically, 38% of 24 patients had watery discharge and 13% had Peutz-Jeghers syndrome, while pathologically, most patients were low stage (I or II) (83%). Over the 2-year follow-up of 17 patients, 82% was free from disease. The patients with more aggressive tumors or an unfavorable prognosis that manifested as tumor recurrence or metastasis tended to have invasion, watery discharges, high stages (III or IV) (100%) and solid lesions, metastases, and associated ovarian lesions (67%). Awareness of imaging features as well as clinicopathologic manifestations of adenoma malignum can aid in accurate diagnosis, treatment, and prediction of prognosis.

A rare case of minimal deviation mucinous adenocarcinoma of the uterine cervix and review of literature

Minimal deviation adenocarcinoma (MDA) is uncommon and accounts for only 1-3% of all cervical adenocarcinomas, and most pathologists diagnose only one or two cases during their professional life. MDA is unusually well-differentiated adenocarcinoma of the cervix formed by neoplastic cells displaying only minimal cytological atypia. Because of the high degree of differentiation, there is a high frequency of failure to diagnose this malignancy histologically. To better understand the presentation of MDA, we are reviewing the clinical, histological, and immunohistochemistry findings in one case.

Adenocarcinoma with Minimal Deviation of the Cervix: What Management?

The cervix adenocarcinoma results in an average 15% of cervical carcinomas. It is most often associated with infection with HPV type 16 or 18. Screening has its particularities compared to squamous cell carcinoma. The minimal deviation adenocarcinoma is a rare histological entity of cervix adenocarcinoma. Cervical cytology provides an imperfect diagnosis of glandular cells compared to squamous lesions, although the 2001 Bethesda system still allows a better management of patients with abnormal glandular cells; the diagnosis is based on histological study. We report a case of 46 years-old woman that was treated for minimal deviation adenocarcinoma of the cervix. It is likely that in future, the screening either cytological or viral must be completed by a specific molecular marker of these lesions.

ASGO 2nd International Workshop on Gynecologic Oncology

ASGO 2nd International Workshop on Gynecologic Oncology

Minimal deviation adenocarcinoma of the cervix and tumorlets of sex-cord stromal tumor with annular tubules of the ovary in Peutz-Jeghers syndrome

We report 2 cases of minimal deviation adenocarcinoma of the cervix and tumorlets of sex cord tumor with annular tubules (SCTATs) of the ovaries, accompanied by Peutz-Jeghers syndrome. Case 1 is a 36-year-old woman and case 2 is a 35-year-old woman. Grossly, the cervix of both cases showed markedly barrel shaped enlargement with an infiltrating tumor. Microscopically, well-differentiated atypical glands were infiltrating into the entire thickness of the cervix. The ovarian masses in case 1 were diagnosed as metastatic carcinoma in mucinous cystadenoma with tumorlets of SCTATs of the ovaries. Multiple scattered tumorlets of SCTATs were also found in the ovary of case 2. By direct DNA sequencing analysis, a frame shift mutation of the STK11/LKB1 gene was identified in case 1. Case 1 represented the more aggressive clinical course, and although the patient received additional combined chemo-radiation therapy, she expired 1 year later. In general, mutation of the STK11/LKB1 gene is associated with poor clinical outcome in malignant tumors accompanied by Peutz-Jeghers syndrome.

Well-Differentiated Adenocarcinoma of the Urinary Bladder with Minimal Deviation Adenocarcinoma-Like Features

Urinary bladder adenocarcinoma is an uncommon disease. The histological diagnosis of bladder adenocarcinoma is usually straightforward. However, bladder carcinoma rarely shows benign-mimicking features. We report on a 64-year-old woman who was diagnosed with urinary bladder adenocarcinoma, which was well differentiated with the features of minimal deviation adenocarcinoma. Most of the tumor cells were slightly atypical, and the tumor was differentiated barely from the benign disease. Careful examination was necessary for a correct diagnosis. The pathology comprised invasive foci with desmoplastic reaction in the extravesicular adipose tissue.

Mucinous Epithelial Lesions in Endometrial Curettage Material

To evaluate the immunohistochemical expression of several benign or malignant mucinous lesions that can be encountered in endometrial curettage material. Nineteen well-differentiated mucinous endometrial carcinomas, 12 papillary mucinous metaplasias, 11 cervical microglandular hyperplasias, 11 endocervical adenocarcinomas, 2 goblet cell metaplasias, 1 minimal-deviation adenocarcinoma, and 1 lobular endocervical glandular hyperplasia entered the study. Immunohistochemistry was performed with the following antibodies against: estrogen receptors, progesterone receptors, vimentin, p16, p63, carcinoembryonic antigen, and Ki-67. Immunohistochemistry could easily distinguish endocervical adenocarcinoma of usual type from all other lesions under study. A Vim(-)/p16(-)/p63(high) signature was found to favor a cervical microglandular hyperplasia, whereas both mucinous endometrial carcinoma and mucinous papillary metaplasia would be preferentially characterized by a Vim(+)/p16(+)/p63(low) immunophenotype. A high Ki-67 expression would be of help in differentiating the latter 2 conditions. Statistically, the expression of estrogen receptors, progesterone receptors, and carcinoembryonic antigen did not aid in the differential diagnosis of these 3 conditions. For the 4 cases representing goblet cell metaplasia, minimal-deviation adenocarcinoma and lobular endocervical glandular hyperplasia, no results could be drawn. In endometrial curettage material, the differential diagnosis of lesions comprising mucinous epithelium might be rendered by combining the immunohistochemical expression of vimentin, p16, p63, and Ki-67. Of all lesions, endocervical adenocarcinoma of usual type is the most easily identified.