Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre.

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

[A tumor of the uterus with a falsely benign aspect]. / Une tumeur utérine d'allure faussement bénigne.

We report the case of a 79 year-old woman, who was admitted in the department of digestive surgery for an occlusive syndrome. The abdominopelvic computed tomography revealed a voluminous mass infiltrating the uterus, the bladder and the colon. A monobloc surgery is performed. The histopathological examination evidences an invasion of these organs by a well-differentiated glandular proliferation composed of epithelial cells without atypia stained with keratin 7 and carcinoembryonar antigen, without expression of p16, hormonal receptors and keratin 20. Ki-67 labeling index was low. The diagnosis of minimal deviation gastric mucinous adenocarcinoma was proposed. This is an uncommon neoplasm comprising approximately 1% of all endocervical adenocarcinomas. This is a difficult histopathological which should be known by pathologist. It is correlated to a poor clinical outcome with a high tendency to lymph node and extra-uterine metastases, as illustrated in our observation.

Adenoma Malignum Presenting With Profound Hyponatremia.

BACKGROUND: Adenoma malignum of the cervix (also referred to as minimal deviation adenocarcinoma) is a rare malignancy. Although previous reports have described adenoma malignum presenting with mucinous vaginal discharge, no reports to our knowledge have described a presentation with profound hyponatremia due to fluid losses. CASE: We present a case of adenoma malignum in a 52-year-old woman who presented with substantial watery vaginal discharge and profound hyponatremia. CONCLUSION: Despite being a rare cervical tumour, adenoma malignum should be considered in the differential diagnosis of watery vaginal discharge. This tumour can present with severe electrolyte disturbances.

Contexte : L'adénome malin du col utérin (aussi connu sous le nom d'adénocarcinome à déviation minime) constitue une tumeur maligne rare. Bien que des signalements précédents aient indiqué que l'adénome malin s'accompagnait d'un écoulement vaginal mucineux, nous n'avons trouvé aucun signalement décrivant la présence concomitante d'une profonde hyponatrémie attribuable à des pertes liquidiennes. Cas : Nous présentons un cas d'adénome malin chez une femme de 52 ans qui connaissait un écoulement vaginal aqueux substantiel et une profonde hyponatrémie. Conclusion : Bien qu'il s'agisse d'une tumeur cervicale rare, l'adénome malin devrait être pris en considération dans le diagnostic différentiel de l'écoulement vaginal aqueux. Cette tumeur peut s'accompagner de graves perturbations de l'équilibre électrolytique.

Case of minimal deviation adenocarcinoma: possible clinical link to lobular endocervical glandular hyperplasia as its origin.

Minimal deviation adenocarcinoma (MDA) is defined as an extremely well differentiated variant of endocervical adenocarcinoma. Several reports have stated that MDA associates with lobular endocervical glandular hyperplasia (LEGH). It is difficult to distinguish LEGH from MDA based on clinical and histologic similarities. There is no definite evidence proving that LEGH is a precursor lesion of MDA. A 45-year-old woman was admitted to our hospital for minute investigation of her neurological disorder. The multiple-cystic lesion at the uterine cervix was identified by magnetic resonance imaging. Based on her normal histological findings and severe underlying conditions, a careful follow-up strategy was adapted. Two years later, atypical glandular cells were observed and the multiple-cystic lesion had increased. Pathological diagnosis of a conization specimen was MDA. Radical hysterectomy was carried out. Pathological examination revealed coexistence of LEGH and MDA. Her clinical course and histological findings suggested the possibility that LEGH might be a precursor lesion of MDA.

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.

A case of uterine adenomyoma of endocervical type that was suspected as minimal deviation adenocarcinoma on biopsy, MRI findings, and literature review.

Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid masses. A premenopausal woman in her 50s was referred to our hospital because of an increasing watery vaginal discharge. A multifocal cyst measuring 5 × 4.5 cm in size projecting into the endocervical canal was revealed on a contrast-enhanced MRI. The fluid within the tumor showed a hypointense signal on T1-weighted imaging (T1WI) and a hyperintense signal on T2-weighted imaging (T2WI). On T2WI, most of the septa within the tumor showed a slightly hyperintense to hypointense signal, whereas some areas revealed a strong hypointense signal; the contrast effect on the septum was satisfactory. On the T2WI taken 2 years previously, the tumor was a 4.5 × 3.5 cm polypoid mass protruding from the posterior endocervical wall. Contrastingly, the current T2WI showed that the stem was no longer identifiable because of tumor growth. Because previous imaging showed that the tumor was a stalked tumor protruding from the posterior endocervical wall, the imaging diagnosis was uterine adenomyoma of the endocervical type. A biopsy suggested the possibility of a minimal deviation adenocarcinoma (MDA). Hence, a total hysterectomy was performed. The final diagnosis confirmed the uterine adenomyoma of endocervical type. Uterine adenomyoma of the endocervical type might be difficult to differentiate from MDA in small biopsy specimens; therefore, evaluation of morphology by MRI is considered important in preoperative diagnosis.

Comparison of Clinicopathological and Prognostic Characteristics Between Minimal Deviation Adenocarcinoma and Gastric-type Endocervical Adenocarcinoma.

BACKGROUND/AIM: Minimal deviation adenocarcinoma (MDA) is an extremely well-differentiated variant of gastric-type endocervical adenocarcinoma (GEA). This study compared the clinicopathological and prognostic characteristics of MDA to those of GEA. PATIENTS AND METHODS: Nine MDAs and 22 GEAs were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological and prognostic information. RESULTS: GEA showed significantly higher stage at presentation, more frequent parametrial extension and lymphovascular space invasion, and recurrence than MDA. Patients with GEA had significantly lower survival rates than those with MDA. None of the cases with MDA exhibited singly dispersed or clustered tumor cells, diffuse stromal desmoplasia, severe nuclear pleomorphism, loss of nuclear polarity, or coarse chromatin, all of which were frequently observed in GEA. CONCLUSION: Significant differences were observed in the clinicopathological characteristics and patient outcomes between MDA and GEA. Further investigations using a larger cohort are warranted to determine the clinical behavior and aggressiveness of MDA.

The Utility and Feasibility of Laparoscopic Surgery in Patients Diagnosed With Cervical Cystic Lesions.

INTRODUCTION: This observation study aimed to differentiate between lobular endocervical glandular hyperplasia (LEGH) and gastric-type mucinous carcinoma (GAS) while evaluating the feasibility and efficacy of laparoscopic surgery in the preoperative diagnosis of cervical cystic lesions. METHOD AND MATERIAL: A retrospective study was conducted to evaluate the diagnostic process and laparoscopic surgical management of cervical cystic lesions suspected to be LEGH or GAS. Preoperatively and postoperatively, MRI, cytology, histology, tumor marker analysis, and surgical outcomes (blood loss during surgery, operative time) were assessed. Six individuals were selected based on magnetic resonance imaging (MRI) results indicating a preoperative suspicion of LEGH or GAS. These patients underwent laparoscopic surgical treatment without indications of malignancy based on preoperative histology or cytology. RESULTS: Initially, all individuals were suspected to have LEGH based on MRI findings. Postoperatively, two patients were diagnosed with LEGH, two with adenocarcinoma in situ (AIS) and minimal deviation adenocarcinoma (MDA), and two showed no notable findings on pathology (one diagnosed endometrioid carcinoma in endometrial tissue). Patients with malignancies exhibited longer surgical times and higher intraoperative blood loss. Preoperatively, no significant variation was observed in maximal lesion diameter between adenocarcinoma and LEGH. However, lesion diameter increased significantly over time in patients with GAS. CONCLUSION: Laparoscopic surgery demonstrated feasibility and provided crucial diagnostic and therapeutic outcomes, with no postoperative recurrence observed in cases of malignancy, despite the challenges associated with preoperative differentiation. These findings underscore the potential of laparoscopic surgery in enhancing both diagnostic accuracy and therapeutic efficacy for cervical cystic lesions, offering promise for improved patient outcomes and management strategies in clinical practice.

Pathology Behind Constant Watery Vaginal Discharge: A Rare Case of Uterine Cervical Minimal Deviation Adenocarcinoma.

Minimal deviation adenocarcinoma (MDA) of uterine cervix is a rare malignant disease with rather poorer prognosis partially due to the early misdiagnosis. Hence, better understanding of early-stage symptoms is critical. We report a case of a 39-year-old woman came to hospital with a chief complaint of "a watery vaginal discharge for 9 months". She was further diagnosed as having uterine cervical minimal deviation adenocarcinoma in cervical LEEP specimen and MDA stage IIIC1 (FIGO 2018 staging-after correction) in post-hysterectomy histopathology. Currently, the definitive treatment is hysterectomy with adjuvant therapy based on staging. This article gives concise symptoms, history, and images of MDA colposcopy finding and histopathology, through the whole process of diagnosis and treatment for future clinical reference.

The importance of correct radiological diagnosis in (adenoma malignum): a case report.

Minimal deviation adenocarcinoma (MDA) of the cervix otherwise known as adenoma malignum is a rare variation of cervical adenocarcinoma. Radiological evaluation plays a great role to ensure an early diagnosis. Here, we report a 48-year-old woman who was presented with a mucoid vaginal discharge 10 years after a supracervical hysterectomy. Despite normal biopsy and cytology, magnetic resonance imaging showed a large cervix and multiple cervical cysts that considered adenoma malignum as a differential diagnosis. She underwent surgery and the pathology confirmed the adenoma malignum. In conclusion, radiologists, as well as gynecologists, and also pathologists may consider MDA among the differential diagnosis in patients with a vaginal discharge and multicysts in the cervix even after hysterectomy despite normal cytology and biopsy.

Minimal deviation adenocarcinoma with elevated CA19-9: A case report.

BACKGROUND: Minimal deviation adenocarcinoma is a rare malignancy with a high rate of misdiagnosis and high aggressiveness, and its diagnosis relies on histopathology. Surgical resection is the preferred and most effective treatment, but the outcomes are often unsatisfactory. CASE SUMMARY: A 60-year-old perimenopausal woman was admitted to the hospital and found to have elevated CA19-9 on physical examination without abdominal pain or vaginal bleeding. Clinical examination and positron emission tomography/computed tomography examination were unremarkable, magnetic resonance imaging examination was suggestive of dominant cervical lesions, and methylation examination was suggestive of malignant lesions. Tissue samples were taken from the suspected cervical lesion, and the final pathologic diagnosis was minimal deviation adenocarcinoma. Based on the pathologic diagnosis of suspected minimal deviation adenocarcinoma, radical abdominal total hysterectomy, bilateral oophorectomy, and pelvic and para-aortic lymph node dissection were performed. The final histological report confirmed minimal deviation adenocarcinoma of the cervix, stage IB2, with lymph node metastasis. Minimal deviation adenocarcinoma is a tumor with aggressive clinical behavior. CONCLUSION: Patients with minimal deviation adenocarcinoma have a lower survival rate than patients with conventional human papillomavirus-related cervical adenocarcinoma. A precise preoperative pathologic diagnosis may reduce the mortality rate due to missed optimal treatment with multiple surgical interventions. To date, there is no therapeutic consensus; therefore, each case must be treated individually.

Worsening cytology and lesion enlargement are useful indicators for malignant transformation of lobular endocervical glandular hyperplasia during follow-up: A case report.

•We report a case of MDA arising from clinical LEGH during 5 years of follow-up.•The first sign suggesting MDA was cellular atypia in endocervical cytology, and was followed by an increase in tumor size.•MDA lesion lacked in stromal reaction and MRI failed to detected MDA.•Worsening cytology and lesion enlargement are important signs for malignant change of LEGH during follow-up.

Whole-exome sequencing of lobular endocervical glandular hyperplasia.

Lobular endocervical glandular hyperplasia (LEGH) was first reported as a benign proliferative disorder of the uterine cervix. However, it currently remains unclear whether it has the biological characteristics of pyloric metaplasia or precursor of minimal deviation adenocarcinoma (MDA)/gastric-type mucinous cervical adenocarcinoma (GAS). Therefore, in the present study we performed whole-exome sequencing on three cases of LEGH collected by laser-microdissection from the frozen tissue sections of surgically removed uteri. Analysis of the results identified 50 somatic variants. After several filtering processes, we identified 13 functional variants, including 12 missense and one insertion-deletion variants. Of these mutations, keratinocyte proline-rich protein, olfactory receptor M4 and zinc finger protein 645 mutations were found in the Catalogue Of Somatic Mutations In Cancer but were not related to carcinogenic diseases. We did not detect any significant copy number alterations or signatures. Although this was a limited case series, we did not identify any variants relevant to the tumorigenesis of LEGH to MDA/GAS, suggesting a metaplastic aspect of LEGH.

Minimal deviation adenocarcinoma (adenoma malignum) of the uterine cervix: clinicopathological analysis of 17 cases.

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors. METHODS: We retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015. RESULTS: The median age of the patients was 47.7 years (33-75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7-99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097-7.746; P=0.032) even after multivariate analysis. CONCLUSION: Early diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.

A case of endocervical minimal deviation adenocarcinoma with varicolored cytopathologic features on Pap smear.

We report a case of minimal deviation adenocarcinoma (MDA) of the uterine cervix showing varicolored cytopathologic features on Papanicolaou (Pap) smear, which may indicate features suggestive of lobular endocervical glandular hyperplasia (LEGH)-adenocarcinoma sequence. A 57-year-old woman presented with a profuse amount of watery vaginal discharge. Gynecological examination revealed a cervical mass with involvement of the right parametrium. Conventional Pap smear showed hypercellularity consisting of approximately 4 types of clusters as follows: (1) clusters showing a monolayered honeycomb sheet of endocervical cells with golden-yellow mucin and bland nuclei, (2) three-dimensional clusters showing varicolored mucin and irregular nuclear overlapping, (3) irregularly shaped clusters showing distorted chicken-wire-mesh appearance with noticeable protrusions of the nuclei and clear or faint varicolored cytoplasm, and (4) crowded clusters showing scarce mucin and nuclear atypia. The surgically resected uterus revealed LEGH-mimicking lesion with fused papillae and a cribriform pattern in the endocervix and many glands exhibiting gastric differentiation that invaded deeper areas of the stroma with a subtle stromal reaction. Compared with histologic findings, two types of clusters, the crowded cluster with scarce mucin and the cluster with distorted chicken-wire-mesh-type appearance, were considered as adenocarcinoma, and the latter was interpreted as a gastric-type adenocarcinoma. Three-dimensional varicolored type clusters showed atypical features, but insufficient atypical features compared with those of adenocarcinoma. Detection of clusters with varicolored mucin on conventional Pap smear may provide a clue for the early recognition of the malignant potential of LEGH on cytology. The chicken-wire-mesh type clusters may be a characteristic cytologic finding of MDA.

Adenoma Malignum Diagnosed Postoperatively in a Case of Fibroid Uterus: Case Report with Review of Literature.

"Minimal deviation adenocarcinoma" of the uterine cervix (MDA), historically known as Adenoma Malignum, is a rare variant of cervical adenocarcinoma. Both the clinicians and pathologists must be vigilant about this entity as it could be mistaken for a benign pathology both clinically and microscopically, which can prove disastrous to the patient as these tumors behave like adenocarcinomas We hereby report an incidentally detected case of AM which was diagnosed in a post-menopausal female postoperatively. We discuss the intraoperative complications, histopathological diagnosis, post-operative management and follow up.

Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports.

Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relevant literature. The two cases at our institution (Kyoto University Hospital, Kyoto, Japan) involved postmenopausal women with a primary complaint of abnormal genital bleeding. Microscopic examination of the hysterectomy specimens indicated a highly differentiated mucinous adenocarcinoma with a desmoplastic stromal reaction. Immunohistochemistry for HIK1083 and/or MUC6 was positive in both cases, suggesting a gastric phenotype. Both patients were diagnosed at an advanced stage, they relapsed or recurred immediately after adjuvant chemotherapy, and eventually succumbed to the disease. The main symptom of gastric-type mucinous adenocarcinoma of the uterine cervix is watery discharge, whereas abnormal genital bleeding in addition to watery discharge is mainly observed in the mucinous type of endometrial adenocarcinoma. Cystic cavities in the tumor are present on MRI in cases of endometrial origin, and prognosis is very poor due to resistance to chemotherapy. Thus, gastric-type mucinous adenocarcinoma of the uterine endometrium exhibits a clinical behavior that is similar to tumors originating from the uterine cervix, but is associated with distinguishing clinical symptoms. The incidence of gastric-type endometrial adenocarcinoma may be higher than expected.

Misdiagnosis Analysis of Cervical Minimal Deviation Adenocarcinoma: a Report of Three Rare Cases and Literature Review.

Cervical minimal deviation adenocarcinoma (MDA) is a rare variant of cervical adenocarcinoma that is difficult to diagnose due to the deep location, endogenous growth pattern, deceptively benign appearance of tumor cells, and lack of connection to human papillomavirus (HPV). Cytological evaluation and biopsies offer suboptimal detection and transvaginal sonography or Magnetic Resonance Imaging (MRI) only reveal multiple lesions that mimic multiple benign nabothian cysts. Besides, standard screening, diagnostic tools, and treatments are not established. Thus, MDA tends to be misdiagnosed with other gynecological diseases. In this study, we examine three cases with extensive abdominal metastasis and adhesions, which are not initially associated clinically with HPV and cervical malignancies. All cases were misdiagnosed as nabothian cysts, endometrial adenocarcinoma or ovarian cancer, though finally diagnosed as MDA by postoperative pathology. Delay in diagnosis and treatment can result in irreversible outcomes. Misdiagnoses are analyzed and suggestions for improving early detection are discussed with a brief review of the literature.

Magnetic resonance imaging of adenoma malignum of the uterine cervix with pathologic correlation: a case report.

Adenoma malignum (AM) is considered a rare subtype of cervical adenocarcinoma. Although previous reports have described magnetic resonance findings, none of these reports evaluated the utility of diffusion-weighted imaging in the differential diagnosis of AM and other multicystic cervical lesions. We present a case report of an AM that did not show restriction on the apparent diffusion coefficient map, which can be explained by the low cellularity of the tumor. This is consistent with the proper correlation between the diffusion imaging and histopathology of the tumor. In this way, AM can present with high apparent diffusion coefficient values, as in benign cervical lesions. Therefore, the combination of a solid multicystic lesion that invades the cervical stroma on T2-weighted magnetic resonance images and the absence of restriction on the apparent diffusion coefficient map are very suggestive of AM.