New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome

Abstract

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.

Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification

“…The initial studies showed that pattern‐based classification correlated with the risk of lymph node metastasis and clinical outcome. Pattern A tumours were limited to Stage I with no evidence of lymph node metastasis or tumour recurrence, whereas pattern C tumours frequently presented at Stage II or higher, had positive lymph nodes in 22.5% and recurred in 19.7%; pattern B tumours also presented at Stage I, and the few lymph node‐positive cases also showed LVI . Similar results were reported by multiple subsequent independent studies .…”

“…Based on the presence or absence of destructive invasion in biopsy material, patients could undergo standard treatment or cone/LEEP procedure, respectively. Destructive invasion in a cone or LEEP would trigger additional surgery …”

Metastases to the ovary arising from endometrial, cervical and fallopian tube cancer: recent advances

“…It is important, therefore, for pathologists and clinicians to be aware of these distinctions and to employ p16 immunohistochemistry and/or HPV detection in order to ensure that the correct diagnosis is reached. Another important consideration is the Silva grading system . An issue identified in previous studies on cases of EAC showing ovarian spread has been the difficulty in separating definite invasion from background adenocarcinoma in situ and in measuring the depth of invasion in cases of very well‐differentiated EAC.…”

Miniseries of reviews: gynecological pathology

“…Instead, it has been found that the the biology of endocervical adenocarcinomas is reflected in its pattern of growth (https://doi.org/10.1007/s00428-018-2312-6). Three growth patterns, known as Silva patterns (named after the senior author of the first description, Elvio Silva), have been described (non-destructive, focally destructive and diffusely destructive) [8,9], which reportedly correlate with the frequency of lymph node metastases and local recurrence and will have strong impact on treatment. Knowledge about this growth pattern-based classification has been further broadened in recent years by several multicenter international collaborative studies.…”

“…This pattern-based model seems simple but is a rather smart approach to cervical tumour pathology, needs to become generally applied in diagnostic pathology and therefore has been adopted by the European working group responsible for the new guidelines for diagnosis and treatment of cervical cancer. The great merit of this system is its recognition of a subgroup of carcinoma with "smooth" nondestructive infiltration irrespective of its size, which requires less aggressive surgical treatment [9]. Future prospective randomized trials will be necessary to finally implement this pattern-based classification.…”