Lobular Endocervical Glandular Hyperplasia Research Articles

Preoperative Differential Diagnosis of Minimal Deviation Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia of the Uterine Cervix

To clarify the preoperative differential diagnosis and management of minimal deviation adenocarcinoma (MDA) and lobular endocervical glandular hyperplasia (LEGH), a multicenter study was performed. A total of 112 patients who underwent conization or a hysterectomy for suspected MDA were collected from 24 hospitals. The pathological diagnosis in each case was determined by a central pathological review board. The diagnostic significance of clinicopathologic findings including results of magnetic resonance imaging (MRI), Papanicolaou (Pap) smears, and testing for gastric mucin was analyzed. The central pathological review identified 37 cases of Nabothian cyst or tunnel cluster, 54 cases of LEGH, 6 cases of MDA, 11 cases of adenocarcinoma, and 4 cases of benign disease. Lobular endocervical glandular hyperplasia was often associated with adenocarcinoma in situ, MDA, and mucinous adenocarcinoma. Three MDA patients had a recurrence, whereas none of LEGH patients had a recurrence irrespective of the type of surgery. On MRI, LEGH appeared as a characteristic multicystic lesion with an inner solid component, whereas MDA showed a predominantly solid pattern. A Pap smear or gastric mucin alone had limited diagnostic power. However, a combination of these findings is useful; that is, a cystic structure with inner solid components on MRI associated with mild glandular atypia and gastric mucin strongly suggested LEGH (24/26, 92%). A solid structure with atypical glandular cells was indicative of MDA or adenocarcinoma (5/5, 100%). The combination of MRI, Pap smears, and gastric mucin will improve the accuracy of the preoperative diagnosis of MDA and LEGH. Patients suspected of having LEGH may need to be treated with less aggressive methods.

Lobular endocervical glandular hyperplasia with extensive mucinous differentiation of endometrium and endometrial mucinous adenocarcinoma in situ: A case report and review of literature

Lobular endocervical glandular hyperplasia with extensive mucinous differentiation of endometrium and endometrial mucinous adenocarcinoma in situ: A case report and review of literature

Pyloric gland metaplasia/differentiation in multiple organ systems in a patient with Peutz–Jegher's syndrome

Peutz-Jegher's syndrome (PJS) involves multiple organ systems and the development of hamartomatous, metaplastic, or neoplastic lesions of different cell lineages. Among them, glandular lesions are the most common, but their properties are obscure. We report here a 53-year-old woman with PJS who developed multiple hamartomatous polyps in the jejunum and mucinous glandular lesions in multiple organ systems: glandular metaplasia in the urinary bladder; lobular endocervical glandular hyperplasia in the uterine cervix; mucinous metaplasia in the right fallopian tube; mucinous adenoma in the left ovary. Histological and immunohistochemical analyses disclosed that all of the intestinal and extra-intestinal lesions were associated with pyloric gland metaplasia/differentiation across the organ systems. In the general population, the organs described above rarely or infrequently show pyloric gland phenotype, to say nothing of trans-organ involvement. It is strongly suggested that commitment to pyloric gland metaplasia/differentiation is closely associated with PJS.

Expression of the insulin-like growth factor-II mRNA-binding protein 3 (IMP3) and carcinoembryonic antigen (CEA) in mucinous minimal deviation adenocarcinoma

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated mucinous adenocarcinoma of the uterine cervix, which always remains a diagnostic dilemma. Lobular endocervical glandular hyperplasia (LEGH), a rare benign lesion of the uterine cervix, is identified as precursor of mucinous MDA. The insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is expressed in a number of cancers and is associated with progression of the tumors. The purpose of this study was to evaluate the expression of the IMP3, carcinoembryonic antigen (CEA), and cyclin-dependent kinase inhibitor p16 INK4a in mucinous MDA and LEGH, and to estimate the possible role of these biomarkers in the diagnosis of mucinous MDA. Twelve samples of MDA, eight samples of lobular endocervical glandular hyperplasia (LEGH), and 20 normal control cases were included in this study. Typical lesions and less well-differentiated lesions coexisted in 11/12 mucinous MDA samples. Positive cytoplasmic expression for IMP3 and CEA was found in less well-differentiated lesions of all 11 mucinous MDA samples, primarily with strong to intermediate staining intensity. The typical well-differentiated lesions of all 12 MDA cases and 8 cases of LEGH showed negativity for both IMP3 and CEA. No exact p16 INK4a positivity was observed in 12 mucinous MDA and 8 LEGH. The significant expression of IMP3 and CEA in less well-differentiated foci of mucinous MDA may be helpful in the diagnosis of mucinous MDA to some extent, particularly in small specimens from cervical biopsy. More cases and in-depth researches are needed to elucidate the potential different mechanisms between typical and less well-differentiated lesions of mucinous MDA.

Aberrant Expression of TFF1, TFF2, and PDX1 and Their Diagnostic Value in Lobular Endocervical Glandular Hyperplasia

Lobular endocervical glandular hyperplasia (LEGH) is a distinct benign glandular lesion expressing gastric gland mucous cell-type mucin (N-acetylglucosaminα1 → 4galactose → R [GlcNAcα1 → 4Gal → R]). To investigate histogenesis and diagnostic markers of LEGH, we examined the immunohistochemical expression profile of gastric surface mucous cell (MUC5AC and TFF1), gastric gland mucous cell (MUC6, TFF2, and GlcNAcα1 → 4Gal → R), gastric pyloric epithelial cell (PDX1), and endocervical cell (keratan sulfate) markers in normal endocervix samples and benign glandular lesions (nabothian cysts, tunnel clusters, and LEGHs). MUC5AC and MUC6 were expressed in normal endocervical mucosa and benign glandular lesions. TFF1, TFF2, GlcNAcα1 → 4Gal → R, and PDX1 were expressed only in LEGH. Keratan sulfate was expressed in normal endocervical mucosa and benign glandular lesions. In LEGH, gastric surface mucous cell and gastric gland mucous cell differentiation were demonstrated, and transdifferentiation from endocervical mucosa into gastric pyloric mucosa was suggested. In addition to GlcNAcα1 → 4Gal → R, TFF1, TFF2, and PDX1 are additional useful markers for LEGH.

Gynecological tumors in patients with Peutz-Jeghers syndrome (PJS)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the development of hamartomatous polyposis in the gastrointestinal tract and melanin-pigmented macules on the skin mucosa. The responsible gene is a tumor suppressor, STK11/LKB1, on chromosome 19p13.3. PJS complicates with benign and malignant tumors in various organs. In gynecology, there has been a particular focus on complications of PJS with sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which are rare diseases. Approximately 36% of patients with SCTAT are complicated with PJS and these patients are characterized by multifocal, bilateral, small and benign lesions that develop into tumors with mucinous to serous ratios of 8:1. In addition, 10% of cases of MDA are complicated with PJS and mutation of STK11, the gene responsible for PJS, has a major effect on onset and prognosis. The disease concept of lobular endocervical glandular hyper-plasia (LEGH) has recently been proposed and LEGH is thought to be a potential premalignant lesion of MDA, however, the relationship between PJS and LEGH remains unclear. Several case reports of PJS patients complicated with gynecological tumors have been published and further studies are needed to determine the underlying causes

Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study

Background:High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells.Methods:Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen.Results:Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH).Conclusion:The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.

PAX2 Distinguishes Benign Mesonephric and Mullerian Glandular Lesions of the Cervix From Endocervical Adenocarcinoma, Including Minimal Deviation Adenocarcinoma

Mesonephric remnants of the cervix are vestiges of the embryonic mesonephric system which typically regresses during female development. Uncommonly, hyperplasia of the mesonephric remnants may occur. The differential diagnosis of exuberant mesonephric hyperplasia includes minimal deviation adenocarcinoma of the cervix, a tumor with deceptively bland morphology for which no reliable diagnostic biomarkers currently exist. PAX2 encodes a transcription factor necessary in the development of the Wolffian duct system, and the protein is expressed in several tumors of mesonephric origin, including renal cell carcinoma, Wilm tumor, and nephrogenic adenoma. We hypothesized that PAX2 may also be expressed in mesonephric lesions of the cervix and may distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma of the cervix. We demonstrated that PAX2 was strongly and diffusely expressed in mesonephric remnants (6 of 6) and in mesonephric hyperplasia (18 of 18); however, no expression was noted in mesonephric adenocarcinoma (0 of 1). PAX2 was expressed in normal endocervical glands (including tunnel clusters and Nabothian cysts) (86 of 86), lobular endocervical glandular hyperplasia (5 of 5), tubal/tuboendometrioid metaplasia (8 of 8), and cervical endometriosis (13 of 14). In contrast, only 2 cases of endocervical adenocarcinoma were positive for PAX2 [invasive adenocarcinoma of the minimal deviation type (0 of 5), usual type (1 of 22), and endometrioid type (1 of 1)]. Adjacent adenocarcinoma in situ, as well as cases of pure adenocarcinoma in situ (0 of 6), were also PAX2 negative. PAX2 expression in the 2 positive endocervical adenocarcinomas was patchy and weak. Most (11 of 15) stage II endometrial endometrioid adenocarcinomas lacked PAX2 expression but 1 of 10 grade 1 tumors and 3 of 5 grade 2 tumors did express PAX2. These results suggest that PAX2 immunoreactivity may be useful to (1) distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma, (2) to distinguish lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma, and (3) to distinguish endocervical tubal metaplasia or cervical endometriosis from endocervical adenocarcinoma in situ. Overall, a strong, diffuse nuclear PAX2 expression pattern in a cervical glandular proliferation predicts a benign diagnosis (positive predictive value 90%, negative predictive value 98%; P<0.001); however, PAX2 should not be interpreted in isolation from the architectural and cytologic features of the lesion as it may be expressed in some stage II endometrial adenocarcinomas involving the cervix.

Clinicopathological significance of cervical adenocarcinoma associated with lobular endocervical glandular hyperplasia

Lobular endocervical glandular hyperplasia (LEGH) is usually assumed to be a benign tumor-like lesion of the glands of the uterine cervix. However, LEGH has been associated with obvious cervical adenocarcinoma. The clinicopathological significance of coexistence of LEGH with adenocarcinoma remains unclear. We microscopically examined the presence or absence of LEGH components in 95 stage Ib cervical adenocarcinomas. Gastric mucin was detected with the use of clone HIK1083. Associations of the coexistence of LEGH components with clinicopathological variables were analyzed. LEGH components were present in 16 cases (16.8%). Gastric mucin was positive in all 16 LEGH components, as compared with only 6 of the 95 adenocarcinoma components. Of the 16 adenocarcinomas with LEGH components, 15 were well-differentiated mucinous adenocarcinomas, and one was poorly differentiated adenocarcinoma. The mortality rate of tumor recurrence was 25% (4 of 16) in patients whose tumors had LEGH components, and 21.5% (17 of 79) in those whose tumors had no LEGH components. There was no significant difference in survival. Early cervical adenocarcinoma was relatively frequently associated with LEGH components. LEGH may be one of the factors related to the development of cervical adenocarcinoma, but adenocarcinoma with LEGH components does not necessarily develop into a highly aggressive “adenoma malignum.”

Reappraisal of synchronous and multifocal mucinous lesions of the female genital tract: a close association with gastric metaplasia

To describe the gastric phenotype of synchronous mucinous metaplasia and neoplasms of the female genital tract (SMMN-FGT). Six patients (mean age 57 years, range 39-83 years) were diagnosed with SMMN-FGT. All six patients had mucinous metaplasia of endometrium, which showed features of lobular endocervical glandular hyperplasia (LEGH)/pyloric gland metaplasia (PGM) in five and was associated with mucinous adenocarcinoma in three. Five patients had mucinous metaplasia of the fallopian tubes, of which three showed borderline features. Two patients had mucinous borderline tumour of the ovary. Five patients had cervical lesions including LEGH/PGM associated with either adenocarcinoma in situ or minimal deviation adenocarcinoma of the cervix. All mucinous lesions were positive for HIK1083 and/or MUC6. One patient with minimal deviation adenocarcinoma involving the vagina died of her disease, whereas five patients, including three with microinvasion and three with positive peritoneal cytology or mucinous ascites, were alive without recurrence after a mean follow-up of 46 months (range 13-102 months). There is a close association between SMMN-FGT and LEGH/PGM. Microinvasion and positive peritoneal cytology may not have an influence on outcome.

Is Lobular Endocervical Glandular Hyperplasia a Cancerous Precursor of Minimal Deviation Adenocarcinoma?

Although lobular endocervical glandular hyperplasia (LEGH) was originally described as a distinct hyperplastic glandular lesion of the uterine cervix, recent studies have raised a question that LEGH may be a cancerous precursor of minimal deviation adenocarcinoma (MDA) and other mucinous adenocarcinomas (MACs) of the uterine cervix. In the present study, we studied LEGH, MDA, and MAC by using molecular-genetic and immunohistochemical methods for chromosomal imbalance, microsatellite instability, human papillomavirus (HPV) infection, and gastric pyloric-type mucin secretion to clarify their relationship. Comparative genomic hybridization revealed recurrent chromosomal imbalances, that is, gains of chromosome 3q and a loss of 1p, which were common to MDA and MAC, in 3 of 14 LEGHs analyzed (21%). LEGHs with chromosomal imbalances showed a degree of cellular atypia in the hyperplastic glandular epithelium. Dual-color fluorescence in situ hybridization confirmed a gain of chromosome 3 fragment in these cervical glandular lesions. HPV in situ hybridization revealed that high-risk HPV (types 16 and 18) was positive in over 80% of MACs, but negative in all LEGHs and MDAs examined. Microsatellite instability was rarely detected in these cervical glandular lesions. Our present study results demonstrated a molecular-genetic link between LEGH and cervical mucinous glandular malignancies including MDA and MAC, and are thought to support the hypothesis that a proportion of LEGHs are cancerous precursors of MDA and/or MAC.

Clinical Impact of Preoperative Screening for Gastric Mucin Secretion in Cervical Discharge by HIK1083-Labeled Latex Agglutination Test

The present study evaluated the clinical impact of preoperative screening for gastric mucin in cervical discharge, using a latex agglutination test with HIK1083, a monoclonal antibody against gastric mucin. HIK1083-labeled latex agglutination tests were performed preoperatively using cervical secretions from 44 patients (group 1) with profuse watery vaginal discharge, multiple cervical cysts on vaginal ultrasonography, or yellowish mucin on a Papanicolaou smear and from 31 patients (group 2) with none of these clinical signs. The results were positive in 26 patients in group 1 and in no patients in group 2. Glandular lesions with a gastric phenotype were identified histologically in all 26 cases positive for the HIK1083 latex test, such as minimal deviation adenocarcinoma, lobular endocervical glandular hyperplasia (LEGH), and pyloric gland metaplasia, but not in negative cases. In 2 cases of LEGH, adenocarcinoma in situ was identified. Screening of gastric mucin in cervical discharge may facilitate preoperative detection of some early cervical adenocarcinoma.

Gross features of lobular endocervical glandular hyperplasia in comparison with minimal‐deviation adenocarcinoma and stage Ib endocervical‐type mucinous adenocarcinoma of the uterine cervix

Gross features of lobular endocervical glandular hyperplasia in comparison with minimal‐deviation adenocarcinoma and stage Ib endocervical‐type mucinous adenocarcinoma of the uterine 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.

Lobular endocervical glandular hyperplasia might become a precursor of adenocarcinoma with pyloric gland features

We report a case of adenocarcinoma with pyloric gland features, which appears to have originated from lobular endocervical glandular hyperplasia (LEGH). Hematoxylin and eosin staining, as well as histochemical and immunohistochemical stainings were performed on formalin-fixed and paraffin-embedded specimens. LEGH was observed in the conization specimens. In the hysterectomy specimens, LEGH, atypical LEGH, and mucinous adenocarcinoma coexisted. The adenocarcinoma was located at a site distant from the transition zone. p16 INK4a immunopositivity was extremely rare. Front formation was observed, and a transition from benign-looking columnar cells of LEGH to adenocarcinoma was recognized. These findings suggested that the adenocarcinoma with pyloric gland features arose from LEGH. LEGH is no longer regarded as a pseudoneoplastic lesion, and it is necessary to consider that LEGH is able to transform into a precursor lesion and to develop into an adenocarcinoma with pyloric gland features.

Endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia showing rapid reaccumulation of hydrometra

Mucinous endocervical adenocarcinoma is characterized by increased watery vaginal discharge, but the early diagnosis is sometimes difficult because biopsy specimen might only serve to sample a superficial part of the tumor. The patient presented with complaints of abdominal distention. No vaginal bleeding or watery discharge was observed. Hydrometra was suspected by imaging studies. Rapid reaccumulation of hydrometra was seen despite drainage. Papanicolaou smear of endocervix and endometrium followed by fractional curettage was performed, but failed to confirm the diagnosis. To investigate the unknown origin of hydrometra, an exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy was performed, followed by pelvic lymphadenectomy because biopsy specimens during operation suggested adenocarcinoma of the cervix. The final pathologic study of surgical specimens revealed mucinous adenocarcinoma, which was located on the proximal area of cervix. Adjacent to carcinoma tissue, lobular endocervical glandular hyperplasia (LEGH) was detected. Pyloric gland mucin (HIK1083), MUC6, and MUC5AC were diffusely immunopositive in the cytoplasm of LEGH cells and the immunoreactivity became weaker in adenocarcinoma cells with tumor progression and loss of differentiation. Based on histopathologic features of the present case, there seems to be a possible link between LEGH and conventional mucinous endocervical adenocarcinomas. The physician should keep in mind the possible existence of endocervical adenocarcinoma in a patient showing rapid reaccumulation of hydrometra, when uterine malignancies are clinically suspected and biopsy finding fails to confirm the diagnosis.

Gastric mucin is expressed in a subset of endocervical tunnel clusters: type A tunnel clusters of gastric phenotype

Gastric mucin expression has been demonstrated in a group of endocervical glandular lesions. The aim of this study was to gain further insight into endocervical lesions with a gastric phenotype. Various types of tunnel clusters (TC) were examined for gastric mucin by alcian blue/periodic acid-Schiff staining and immunohistochemistry for HIK1083. Five of 34 cases of TC expressed gastric mucin defined by PAS dominant neutral mucin and immunopositivity for pyloric gland mucin. Histologically, TC expressing gastric mucin showed lobular arrangements of small to medium-sized glands composed of mucin-rich columnar cells and were classified as Flumann's type A TC. Neither type B TC nor normal endocervical glands expressed PAS dominant neutral mucin and none of them was immunopositive for pyloric gland mucin. Five patients with type A TC of gastric phenotype ranged in age from 33 to 79 years (mean 58 years) and were multiparous. Type A TC of gastric phenotype, ranging from 2 to 4 mm in maximum diameter, were incidental findings in hysterectomy specimens. Type A TC of gastric phenotype could be related to lobular endocervical glandular hyperplasia of gastric phenotype. The pathogenesis of gastric metaplasia in TC remains unclear.

Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection

Objectives. The aim of this study was to investigate differences in the process of carcinogenesis between adenocarcinoma coexistent with LEGH and conventional adenocarcinoma. And we intend to describe appropriate treatment plans for LEGH in this study. Methods. Using the surgical pathology files of patients who visited the University of Yamanashi Hospital, Yamanashi Central Hospital and Kofu Municipal Hospital between 1996 and 2005, pathological diagnoses were reevaluated based on criteria for the diagnosis of LEGH by Nucci et al. As for the cases including adenocarcinoma with LEGH: (a) we created a map showing position of the LEGH component and adenocarcinoma component and squamo-columnar junction (SCJ) in HE-stained specimens, (b) immunohistochemical staining was performed using antibodies to CEA, HIK1083 and p53, and (c) detection of HPV DNA was performed using PCR and in situ hybridization (ISH). Results. Endocervical adenocarcinoma was observed coexistent with LEGH in 5 cases (19.2%). (a) LEGH was located in a remote place from the SCJ. Sizes of lesions in the 5 cases ranged from 18 to 35 mm in width and 7 to 16 mm in depth. (b) HIK1083 was diffusely immunopositive in the cytoplasm of LEGH component and focal immunopositive in 4 cases with adenocarcinoma component. Immunopositivity for CEA was seen in the cytoplasm of adenocarcinoma component in 4 cases. Immunopositivity for p53 was seen in adenocarcinoma component nuclei in 2 cases. (c) HPV DNA was not detected using PCR and ISH in either LEGH or adenocarcinoma components. Conclusions. The present study suggests that clear differences exist in the process of carcinogenesis between adenocarcinoma associated with LEGH and conventional adenocarcinoma. LEGH may represent a precursor of cervical adenocarcinoma independent of HPV infection. As LEGH displays characteristics of precancerous mucinous adenocarcinoma, surgical treatment should be considered for LEGH growing beyond a certain size.

P16INK4a Overexpression Independent of Human Papillomavirus Infection in Lobular Endocervical Glandular Hyperplasia

A high rate of human papillomavirus (HPV) infection has been reported in cervical cancer and precancerous lesions. Many studies also have shown that p16INK4a overexpression is of diagnostic value for high-risk HPV-related cervical cancer and precursors. Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. There is one report about HPV infection and few studies on p16INK4a expression in LEGH. Therefore, we 1) detected HPV infection and examined p16INK4a expression and 2) observed the relationship between HPV and p16INK4a overexpression in LEGH. The immunohistochemical expression of p16INK4a was studied in 24 cases of LEGH. HPV DNA was also evaluated in these cases using a polymerase chain reaction technique. Strong (++) p16INK4a immunoreactivity was observed in 10 (41.7%) of the 24 LEGH cases; a moderate (+) pattern was observed in 9 (37.5%) cases; a weak (+) pattern was observed in 2 (8.3%) cases; and the remaining 3 (12.5%) cases showed negative expression. Overall, p16INK4a overexpression was seen in 87.5% of the cases (21/24). HPV DNA was not detected in any of the 24 LEGH cases. These results suggest that p16INK4a overexpression is independent of HPV infection in LEGH.

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses

We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.