Criteria to Evaluate Tumor Enlargement During the Active Surveillance of High-Risk Thyroid Nodules: Which is Better, Diameter or Volume?

INTRODUCTION: Tumor enlargement is the most common parameter identifying disease progression during active surveillance, but the value and significance of the changes in tumor diameter and volume in the evaluation of tumor growth have not been compared. METHODS: This cohort study included 468 patients with high-risk thyroid nodule, in whom nodule size change was monitored using ultrasound, to compare the changes in tumor diameter and volume in assessing tumor growth. RESULTS: A total of 569 high-risk thyroid nodules were found in the 468 patients. A total of 14 nodules (2.5%) showed a diameter increase ≥ 3 mm. The number of nodules with a peak volume change exceeding 50% and 100% was 185 (32.5%) and 86 (15.1%), respectively. Among the 555 stable nodules, the number of nodules with volume fluctuations exceeding 50% and 100% was 171 (30.8%) and 72 (13.0%), respectively. Among 212 stable nodules at the baseline and in the first three follow-up, the percentage of peak volume fluctuations exceeding 50% (48.5% vs. 28.5%, p = 0.004) and 100% (26.5% vs. 8.3%, p < 0.001) in the nodules with the sum of three diameters (SOTDs) ≤ 1 cm was significantly higher than that of nodules with SOTDs > 1 cm. A statistically significant difference was also found in the range distribution of SOTDs ≤ 1 cm and SOTDs > 1 cm (p = 0.007). CONCLUSIONS: Volume is not an appropriate method for determining tumor growth. Tumor diameter measurement alone serves as a better surrogate for disease progression in sonographically high-risk thyroid nodules than volume.

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China.

INTRODUCTION: Active surveillance (AS) is considered an alternative to immediate surgery (IS) for low-risk papillary thyroid microcarcinoma (PTMC) patients. However, it is difficult to decide between AS and IS due to limited evidence regarding risks and benefits for patients in China. METHODS: This study prospectively enrolled 485 patients with highly suspicious thyroid nodules

Endoscopic ultrasound-guided tissue acquisition with or without rapid on-site evaluation for solid pancreatic lesions: five years of experience from a single center.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) by EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) is a standard diagnostic procedure for solid pancreatic lesions. Whether rapid on-site evaluation (ROSE) should be used to support EUS-TA remains controversial. Here we assessed the diagnostic performance of EUS-TA with or without self-ROSE for solid pancreatic masses. METHODS: Three hundred and seventy EUS-TA cases with self-ROSE and 244 cases without ROSE were retrospectively enrolled between August 2018 and June 2022. All procedures including ROSE were performed by the attending endoscopist. Clinical data, EUS characteristics, and diagnostic performance for distinguishing benign from malignant solid pancreatic masses including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between groups. RESULTS: Self-ROSE improved the diagnostic accuracy of solid pancreatic lesions by 16.7% in the EUS-TA group (p < 0.001) and by 18.9% in the EUS-FNA alone group (p < 0.001). Self-ROSE also improved the diagnostic sensitivity by 18.6% in the EUS-TA group (p < 0.001) and by 21.2% in the EUS-FNA alone group (p < 0.001). Improvements in the diagnostic accuracy by self-ROSE in the EUS-FNB group were not significant. 2.2 ± 0.7, 2.4 ± 0.9, 2.3 ± 0.7, 2.5 ± 0.9, 2.1 ± 0.6, and 2.1 ± 0.7 needle passes were required in the EUS-TA, EUS-FNA, and EUS-FNB with or without self-ROSE groups, respectively. CONCLUSIONS: Self-ROSE significantly improved the accuracy and sensitivity of EUS-FNA alone and EUS-TA diagnosis of solid pancreatic lesions and helped to reduce needle passes during the procedure. Whether self-ROSE benefits EUS-FNB and whether EUS-FNB alone is comparable to EUS-FNA with self-ROSE require further clarification.

Active surveillance of highly suspicious thyroid nodules cohort in China shows a worse psychological status in younger patients.

Background: Active surveillance has been considered a safe alternative to surgery for low-risk papillary thyroid microcarcinoma. This study aimed to assess the oncological outcomes and psychological status of active surveillance of highly suspicious thyroid nodules ≤10 mm in China. Methods: This prospective single-center cohort study enrolled 336 patients with highly suspicious thyroid nodules for active surveillance to assess oncological outcomes and psychological status. The psychological status of patients was assessed by two different questionnaires and compared among different patient groups. Results: During a median follow-up period of 28.5 months, eight patients underwent delayed surgery for tumor enlargement and one for lymph node metastases. The cumulative incidence of disease progression at 5 and 10 years was 6.0% and 12.8%, respectively. Patients who underwent delayed surgery had no permanent complications, and no patient had distant metastasis or death. Patients ≤30 years old had a higher baseline anxiety score (4.9 vs. 3.8, p=0.024), a higher proportion of baseline anxiety score, i.e., ≥8 points (24.0% vs. 12.6%, p=0.033), and a worse baseline emotional function (62.7 vs. 70.7, p=0.013) than patients >30. During AS, patients ≤30 years of age had higher overall anxiety levels (p=0.005) and a worse overall emotional function (p=0.001). Conclusions: Active surveillance in Chinese patients with highly suspicious subcentimetre thyroid nodules has good oncological outcomes and can be used as a safe alternative to surgery. Younger patients (≤30) show a worse psychological status; therefore, more attention should be paid to younger patients.

Extranodal natural killer/T-cell lymphoma nasal type with extensive ocular tissue involvement: a case report.

BACKGROUND: To report a rare case of extranodal natural killer/T-cell lymphoma (ENKTL), nasal type related to extensive ocular tissue, including conjunctiva, ciliary body, vitreous and retina. CASE PRESENTATION: A 52-year-old woman who had been treated by radiotherapy for ENKTL, nasal type in the right nasal cavity presented with a dramatic deterioration of vision in right eye. Physical and accessory examination showed extensive ocular tissue related, including conjunctiva, ciliary body, vitreous and retina. Vitreous specimen and conjunctiva biopsy revealed the presence of ENKTL, nasal type in the right eye. She was treated with systemic and ophthalmic chemotherapy, her ocular symptoms significantly improved, and systemic condition remained stable 7 months after the diagnosis. CONCLUSIONS: Extranodal natural killer/T-cell lymphoma, nasal type is an aggressive disease and may relate extensive ocular tissue and course dramatic vision deterioration. It is important to observe ocular related and begin aggressive combined therapy as early as possible after diagnosis.

Value of contrast-enhanced ultrasound combined with percutaneous ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic lesions.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment. METHODS: Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups. RESULTS: This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group (P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant. CONCLUSIONS: Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

Endometriosis-Related Pleural Effusion: A Case Report and a PRISMA-Compliant Systematic Review.

Background: Endometriosis-related pleural effusion (PE) is a relatively rare but treatable cause of bloody PE. The clinical characteristics and outcome of patients with endometriosis-related PE remain unknown. Objectives: We present a case of endometriosis-related PE diagnosed on pleural fluid cytology. A systematic review of all endometriosis-related PE cases in literature was conducted to elucidate the clinical characteristics, explore the diagnostic yield of pathological examinations, and to summarize the outcomes of therapeutic approaches in this disease. Methods: A case of endometriosis-related PE diagnosed in study hospital was reported. PubMed, Web of Science, and EMBASE were searched for publications pertaining to cases of endometriosis-related PE using predefined search terms. This case and those identified from PubMed, Web of Science, and EMBASE were analyzed. Results: A total of 67 patients were included. Catamential symptoms were presented in 30 (44.8%) patients. Dyspnea was presented in 50 patients (74.6%), followed by right chest/shoulder pain in 34 (50.7%) and cough in 18 (26.9%). 82.8% of the patients had concomitant pelvic endometriosis and 76.7% was infertile or nulliparous. The diagnostic yield of pleural fluid cytological examination, percutaneous pleural biopsy, and surgical biopsy was 9.0, 45.5, and 78.7%, respectively. The patients who received surgery-based therapy had a significantly longer time to relapse than those who received progestational agents or GnRH analogs alone (P = 0.025) or hysterectomy and bilateral salpingoophorectomy (HBSO) (P = 0.040). Conclusions: High clinical awareness of pleural endometriosis is essential in all female with hemorrhagic PE, especially in young females who have infertility and/or pelvic endometriosis. Plerual fluid cytology might be a simple minimally invasive and cost-effective modality in the diagnosis of endometriosis-related PE. Treatment is challenging due to high recurrence and the optimal management of endometriosis-related PE needs further evaluation. The combined approach by surgery and hormonal therapy may achieve the best relapse-free survival.

A new needle-based confocal laser endomicroscopy pattern of malignant pancreatic mucinous cystic lesions (with video).

BACKGROUND AND OBJECTIVES: The diagnosis of malignant pancreatic cystic lesions (PCLs) remains challenging. Needle-based confocal laser endomicroscopy (nCLE) is an emerging promising imaging technique capable of real-time in vivo microscopic imaging of the cyst wall. We aimed to develop and validate a new nCLE diagnostic criteria for malignant mucinous cystic lesions (MLs). METHODS: Patients referred for EUS-FNA of indeterminate PCLs with at least one worrisome features according to Fukouka consensus were consecutively prospectively enrolled from July 2016 to July 2018. The final diagnosis was based on surgical histology, cytopathology, or committee consensus. Five investigators nonblindly reviewed nCLE features and identified potential diagnostic feature for malignant MLs, which was also reviewed in histology imaging accordingly. Furthermore, the nCLE diagnostic feature was evaluated with an independent nCLE dataset by two investigators in a double-blind manner. RESULTS: A nCLE pattern of dark aggregates of neoplastic cells was identified as diagnostic for MLs, which was consistent with histological findings of irregular branching and budding in malignant MLs. An independent validation revealed that the accuracy, sensitivity, and specificity of this feature for the diagnosis of malignant MLs were 94%, 75%, and 100%, respectively. CONCLUSION: The new nCLE criterion is promising for diagnosis of malignant MLs which warrants further confirmation in large cohort.

The value of contrast-enhanced ultrasound for sentinel lymph node identification and characterisation in pre-operative breast cancer patients: A prospective study.

OBJECTIVE: To explore the feasibility of sentinel lymph node (SLN) identification by contrast-enhanced ultrasound (CEUS) in pre-operative breast cancer patients and the value of enhancement patterns for diagnosing lymph node metastases and characterising axillary nodal burden. METHODS: 110 consecutive breast cancer patients were enrolled. Before the surgery, microbubbles were injected intradermally. The lymphatic drainage pathway was detected to identify the SLNs. Blue dye and indocyanine green (ICG) fluorescence were used to trace SLNs during the operation. The enhancement patterns of SLNs were recorded and compared with the final pathological diagnosis. RESULTS: SLN detection rate was 96.4 % of 110 patients, 134 SLNs were detected in total. The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of predicting SLNs metastases by CEUS enhancement patterns were 100 %, 52.0 %, 43.4 %, 100 % and 64.9 %, respectively. No metastatic SLNs were presented as homogeneous enhancement. Low nodal burden with 0-2 SLN metastases in 92.5 % nodes presented as heterogeneous enhancement. No enhancement pattern was proved to be SLN metastases in 100 % patients. CONCLUSIONS: CEUS is a feasible approach for SLN identification. CEUS enhancement patterns can be helpful in recognising metastatic SLNs and nodal burden. KEY POINTS: • CEUS is a feasible approach for SLN identification and characterisation. • The enhancement patterns on CEUS can be helpful in recognising metastasised SLNs. • Homogeneous enhancement pattern has the highest negative-predictive value.

Value of preoperative ultrasound-guided fine-needle aspiration for localization in Tc-99m MIBI-negative primary hyperparathyroidism patients.

To evaluate the value of preoperative ultrasound-guided fine-needle aspiration (UG-FNA) of ultrasound-detected suspicious parathyroid nodules for localization in Tc-99m MIBI-negative primary hyperparathyroidism patients.From May 2008 to December 2016, Tc-99m MIBI-negative primary hyperparathyroidism patients with ultrasound-detected suspicious cervical nodules underwent UG-FNA. The sample obtained from the solid component of the nodule was subjected to cytological evaluation and immunohistochemical staining. The sample obtained from the cystic component of the nodule or solid nodules was subjected to parathyroid hormone determination. After aspiration, the nodules underwent surgical resection or follow-up.Fifteen nodules (5 cystic, 5 cystic and solid, and 5 solid) from 15 patients were subjected to UG-FNA. Aspirate samples were obtained from 12 of the nodules, and the parathyroid hormone (PTH) levels of these samples were markedly elevated (range: 302- >2500 pg/mL). The samples obtained from the solid components of the 4 cystic and solid and 4 solid nodules were subjected to cytological evaluation, and parathyroid cells were identified in 5 of them. Of these 5 cases, 4 were subjected to immunohistochemical staining, which revealed PTH positivity in the cell block. The UG-FNA results suggested that the suspicious nodules were all parathyroid lesions. The surgical pathology results of 13 cases confirmed the UG-FNA results; the follow-up of 2 cases did not reveal any significant change.The cytological evaluation, immunohistochemical staining, and aspirate fluid PTH determination of UG-FNA were helpful for preoperative localization in Tc-99m MIBI-negative primary hyperparathyroidism patients with ultrasound-detected suspicious parathyroid nodules and can be applied selectively or in combination. Aspirate sample PTH determination should be preferred for nodules with cystic components. Further prospective study with large population is needed to confirm our conclusions.

Partially cystic thyroid nodules in ultrasound-guided fine needle aspiration: Prevalence of thyroid carcinoma and ultrasound features.

Partially cystic thyroid nodules (PCTNs) are common on ultrasound (US). However, there are insufficient data on the prevalence of thyroid carcinoma among such nodules. The purpose of this study was thus to evaluate the prevalence and differentiation of partially cystic thyroid cancers in US-guided fine needle aspiration (FNA).A total of 1342 consecutive patients with 1360 thyroid nodules underwent prospective US diagnosis and FNA biopsy. In total, 281 nodules (20.7%) were partially cystic lesions. The nodules were prospectively analyzed based on US features (ie, solid portion positions, shapes, margins, and microcalcifications) and US diagnosis (benign, suspicious, or malignant).Of the 281 partially cystic lesions, 22 nodules (8%) had inadequate FNA results, 14 nodules were diagnosed as malignant, 9 were suspicious for malignancy, and 236 were benign on FNA. Thirteen cancers were confirmed upon surgical histopathology examination or FNA, yielding a 4.6% rate of malignancy. Twelve of these cancers were papillary carcinomas, and 1 was an anaplastic carcinoma. The following individual sonographic characteristics had a statistically significant association with thyroid cancer: nodule composition (solid portion ≥50%, P = .000), eccentric solid portion (P = .001), irregular nodule shape (P = .000), microcalcification (P = .000), and intranodular vascularity (P = .001). The sensitivity, specificity, and accuracy of the US-based diagnoses were 84.6%, 84.0%, and 84.0%, respectively.Fewer than 5% of the partially cystic nodules in this FNA series were malignant. Sonographic characteristics can be used to prioritize nodules for FNA biopsy.

Papanicolaou Society of Cytopathology new guidelines have a greater ability of risk stratification for pancreatic endoscopic ultrasound-guided fine-needle aspiration specimens.

The Papanicolaou Society of Cytopathology has recently proposed a standardized terminology and nomenclature guidelines for pancreatic cytology. However the risk of malignancy associated with the new guidelines has been scarcely studied. In this study, a series of pancreatic cytology cases obtained by endoscopic ultrasound-guided fine-needle aspiration from 294 Chinese patients were retrospectively re-categorized into six categories according the new guidelines. The risks of malignancy were 18.1% for "negative," 20.0% for "neoplastic," 57.1% for "nondiagnostic," 69.2% for "atypical," 87.5% for "suspicious," and 100.0% for "positive" respectively. The area under the receiver operating characteristic curve was 0.93 (95% Confidence Interval, 0.90-0.96), which was significantly higher than that associated with old classification system (0.82; 95% Confidence Interval, 0.77-0.87) conventionally used in China. Our investigation demonstrated that the new guidelines have a greater ability of risk stratification than the old classification system conventionally used in China. This may be helpful in giving better predictions of malignancy, thus leading to more personalized treatment strategies.

Role of Thyroid Ultrasound in the Diagnosis of Thyroid Nodules with Atypia of Undetermined Significance.

Objective To evaluate the role of ultrasound for thyroid nodules with atypia of undetermined significance(AUS).Methods From January 2014 to December 2015,83 thyroid nodules with AUS diagnosed by ultrasound-guided fine-needle aspiration biopsy were collected from 1984 subjects. On the basis of ultrasonic features,each thyroid nodule was prospectively classified into one of three categories: low suspicion for malignancy,intermediate suspicion for malignancy,and high suspicion for malignancy. Results Among 83 lesions,19 lesions(22.9%) were confirmed malignant,8 lesions (9.6%)were benign,56 lesions (67.5%)had no abnormal changes during clinical follow-up. The nodules were solitary in 36 cases (43.4%)and multiple in 47 cases(56.6%).The maximum diameter was (1.2±0.7)cm. Based on the ultrasonic feature of 19 malignant cases,16 cases (84.2%) were classified as high suspicion for malignancy,2 cases(10.5%) as intermediate suspicion for malignancy,and 1 case(5.3%) for low suspicion for malignancy. Univariate and multivariate analyses revealed that the degree of malignancy of thyroid nodules was significantly associated with ultrasound image classification[OR=9.23(2.96-28.79),P=0.00],but not with age,gender,nodule number,and nodule size (all P>0.05).Conclusion Ultrasound diagnosis by using the present thyroid ultrasound classification system can be helpful for distinguishing malignant and benign AUS thyroid nodules.

Mutant-specific BRAF and CD117 immunocytochemistry potentially facilitate risk stratification for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens.

The study aims to test whether combination of mutant-specific BRAF and CD117 immunocytochemical (ICC) staining stratifies probability for papillary thyroid carcinoma (PTC) in thyroid fine-needle aspiration biopsy (FNAB) specimens. A consecutive cohort of cases diagnosed as atypia of undetermined significance (AUS) or suspicious for malignancy-suspicious for papillary thyroid carcinoma (SM-SPTC) from 30 December, 2011 to 23 October, 2014 in a single institute was enrolled. Forty cytologically benign and 50 cytologically diagnosed PTC within the same time span were also included. CD117 and mutant-specific BRAF (BRAF VE1) ICC staining was performed. Association of BRAF VE1 and CD117 expression with final diagnosis was analyzed. Both BRAF VE1 and CD117 showed good performance in distinguishing PTC from benign nodules. Combination of BRAF VE1 and CD117 stratified 180 cases into three categories: BRAF VE1 positive regardless of CD117 expression (ICC-malignant), BRAF VE1 negative plus low level of CD117 expression (ICC-intermediate), and BRAF VE1 negative plus high level of CD117 expression (ICC-benign), which was associated with 100, 75.6, and 0 % of malignancy. Combination of mutant-specific BRAF and CD117 ICC may potentially facilitate the PTC risk stratification in FNAB thyroid nodule specimens.

Automated quantification of DNA aneuploidy by image cytometry as an adjunct for the cytologic diagnosis of malignant effusion.

DNA aneuploidy is a cancer biomarker, which may have a potential diagnostic value in body effusion specimen. DNA aneuploidy is determined by measuring the DNA content of tested cells and comparing them with diploid cells (2c). In order to assess the value of automated DNA image cytometry (DNA-ICM) in the cytologic diagnosis of effusion, we measured DNA ploidy using an automated DNA-ICM analysis system in 126 consecutive effusion specimens and followed the cases for histologic diagnosis. Half of each effusion specimen was used to prepare cytologic smears for conventional cytologic diagnosis, while the other half was used to prepare a monolayer slide stained by Feulgen stain for automated ICM. By using Youden index, we found that 4 cells exceeding 2.5c is the optimal cut off value for aneuploidy, which has a sensitivity of 88.3% and specificity of 100% for diagnosis of malignant effusion. We also found that the DNA aneuploidy thresholds used for other types of cytologic specimens cannot be used in the diagnosis of effusion specimens. Our study demonstrated that automated DNA image cytometry is a simple, practical and cost-effective method for adjunct diagnosis of malignant effusion.

[Tubulolobular carcinoma of breast: a clinicopathologic study of 8 cases].

OBJECTIVE: To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC). METHODS: Eight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34ßE12 and CK8. RESULTS: Among the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34ßE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now. CONCLUSIONS: TLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34ßE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.

[Role of HPV DNA detection and p16(INK4A) protein expression in diagnosis of endocervical adenocarcinoma].

OBJECTIVES: To evaluate the significance of p16(INK4A) protein expression and positivity for HPV DNA in distinguishing between endocervical and endometrial adenocarcinoma. METHODS: Expression of p16(INK4A) protein in 30 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was assessed by immunohistochemistry. In-situ hybridization for human papillomavirus (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma. RESULTS: The positive rate for p16(INK4A) in endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma. CONCLUSIONS: The expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression pattern can serve as a useful immunohistochemical marker in the differential diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive than HPV DNA testing in distinguishing between endocervical and endometrial adenocarcinoma, especially in biopsy or curettage specimens.