We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphvascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors.

A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma. Tumors with pattern C showed diffusely infiltrative glands with associated extensive desmoplastic response. In total, 352 cases (all FIGO stages) from 12 institutions were identified. Mean patient age was 45 years (range, 20 to 83 y). Forty-nine (13.9%) cases demonstrated lymph nodes (LNs) with metastatic endocervical carcinoma. Using this new system, 73 patients (20.7%) were identified with pattern A tumors (all stage I); none had LN metastases and/or recurrences. Ninety patients (25.6%) were identified with pattern B tumors (all stage I); only 4 (4.4%) had LN metastases; 1 had vaginal recurrence. The 189 (53.7%) remaining patients had pattern C tumors; 45 (23.8%) of them had LN metastases. This new classification system demonstrated 20.7% of patients (pattern A) with negative LNs, and patients with pattern A tumors can be spared of lymphadenectomy. Patients with pattern B tumors rarely presented with metastatic LNs, and sentinel LN examination could potentially identify these patients. Aggressive treatment is justified in patients with pattern C tumors.

Pim-2 is an important prosurvival gene, which might result in activation of enhanced anti-apoptotic pathway, leading to a more aggressive phenotype of PCa. Pim-2 may become a target for novel therapeutic strategies.