Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association.

Tissue biomarkers have been of increasing utility for scientific research, diagnosing disease, and treatment response prediction. There has been a steady shift away from qualitative assessment toward providing more quantitative scores for these biomarkers. The application of quantitative image analysis has thus become an indispensable tool for in-depth tissue biomarker interrogation in these contexts. This white paper reviews current technologies being employed for quantitative image analysis, their application and pitfalls, regulatory framework demands, and guidelines established for promoting their safe adoption in clinical practice.

Clinicopathologic and Immunohistochemical Characterization of Dedifferentiated Endometrioid Adenocarcinoma.

Dedifferentiated endometrioid adenocarcinoma (DEAC) of the uterus or ovary is characterized by the coexistence of low-grade endometrioid adenocarcinoma and an undifferentiated carcinoma (UC) with solid sheets of medium-sized monotonous epithelial cells. This admixed carcinoma has not been widely recognized, because the solid areas of UC have usually been misdiagnosed as a solid form of FIGO grade 3 endometrioid adenocarcinoma. These tumors have been shown to be clinically aggressive; therefore, accurate diagnosis is necessary for proper patient management. We reviewed our experience with DEACs and compared them with grade 3 endometrioid carcinomas regarding their clinicopathologic, morphologic, and immunohistochemical features. Our results indicate that DEACs are clinically aggressive tumors presented at advanced stages with vascular invasions in 73% and lymph node metastases in 46%. Thirty-eight percent of cases also showed distal metastases. Clinical follow-up data revealed that all patients had either recurrent or metastatic diseases within 3 years of diagnosis, except 1 patient who remained disease free for 3 years after diagnosis. Morphologically, UC components of DEACs were composed of diffuse sheets/solid nests of medium-sized epithelial cells with scant to moderate cytoplasm, uniform vesicular nuclei, and inconspicuous nucleoli. Although UC components of DEACs are variably positive for cytokeratin, EMA, and ER, they are mostly negative for PAX8, except 1 case. Instead, well-differentiated components of DEACs and solid grade 3 endometrioid carcinoma retained all these markers. Our results indicate that DEACs exhibit significantly different clinicopathologic features from grade 3 endometrioid adenocarcinoma, and a combination of immunohistochemical stains can be helpful to differentiate them from each other.

Follow-up outcomes in a large cohort of patients with HPV-negative LSIL cervical screening test results.

OBJECTIVES: Cervical screening guidelines now recommend repeat cotesting of patients aged 30 years and older having a human papillomavirus (HPV)-negative low-grade squamous intraepithelial lesion (LSIL) in 1 year as preferred management. Only limited follow-up data on patients with HPV-negative LSILs are available from routine US clinical practice settings. METHODS: In total, 680 patients with Hybrid Capture 2 (Qiagen, Hinden, Germany) high-risk HPV-negative LSIL ThinPrep (Hologic, Marlborough, MA) results were identified. Patients' ages and histopathologic, cytologic, and HPV follow-up results were identified. RESULTS: Among 680 patients with HPV-negative LSILs, 468 had follow-up within 1 year. During the study period, 14 (3.0%) of 468 had follow-up high-grade squamous intraepithelial lesion (HSIL) and 184 (39.3%) LSIL findings. No diagnoses of cervical carcinoma were documented. There were no significant follow-up differences between age groups. Of the 321 patients who had follow-up HPV testing, 271 (84.4%) had negative and 50 (15.6%) had positive HPV results. CONCLUSIONS: This is the largest study documenting follow-up results for patients with HPV-negative LSIL results based on prevalent US FDA-approved co-testing methods from one collection vial. These data document that risk for follow-up HSILs in these patients is low and also that no cervical cancers were diagnosed. These findings support recent recommendations for repeat co-testing after 1 year as an appropriate option for patients with HPV-negative LSIL results.

Long-term follow-up results from women with cervical adenocarcinoma in situ treated by conization: an experience from a large academic women's hospital.

OBJECTIVES: Cervical adenocarcinoma in situ (AIS) is the precursor to adenocarcinoma, and early management will often prevent the occurrence of invasive adenocarcinoma. Conservative treatment with conization has been proposed for the initial treatment for cervical AIS. To evaluate the risk of residual/recurrent disease after conization, we investigated the long-term follow-up results for patients with cervical AIS treated by conization. MATERIALS AND METHODS: One hundred thirty-six patients with a biopsy diagnosis of cervical AIS followed by conization were followed up with cytologic, histologic, and human papillomavirus testing. RESULTS: The rate of residual AIS in the following hysterectomy was significantly increased in patients with positive margins on the conization (48.6%, 17/35) compared to patients with negative margins (0/30). No significant disease was identified in patients treated by hysterectomy as primary treatment. More importantly, only 2 patients with conization as primary management had adenocarcinoma or focal AIS, respectively, during a long-term follow-up period (mean, 45 mo). However, one of them had positive margin on the conization and did not proceed to further treatment. The other one had negative margin on the conization but only had focal AIS on the hysterectomy. Human papillomavirus-positive rate showed no significant difference between patients treated by conization and patients treated by hysterectomy during the long-term follow-up. CONCLUSIONS: Therefore, if a negative resection margin is achieved, conservative management with conization and careful surveillance is suitable for patients with cervical AIS and desire for future childbearing.