Uterine smooth muscle tumors of uncertain malignant potential (STUMP): a clinicopathologic analysis of 16 cases

Am J Surg Pathol. 2009 Jul;33(7):992-1005. doi: 10.1097/PAS.0b013e3181a02d1c.

Abstract

Background: The current World Health Organization classification indicates that a uterine smooth muscle tumor that cannot be histologically diagnosed as unequivocally benign or malignant should be termed "smooth muscle tumor of uncertain malignant potential" (STUMP). STUMPs represent a heterogeneous group of rare tumors that have been the subject of only a few published studies, some of which lack detailed clinicopathologic details and/or follow-up data. More recently, it has been suggested that immunohistochemical staining may be helpful in the diagnosis of STUMPs.

Design: The clinicopathologic features of 16 cases of STUMP that exhibited usual smooth muscle differentiation, diagnosed between 1992 and 2006 from 11 hospitals, were studied and classified into 4 subgroups using terminology and criteria described by Stanford investigators. Immunohistochemical stains for p16, p53, MIB1 (ki-67), and estrogen and progesterone receptors were performed. The results were compared with those in the literature.

Results: The tumors were classified as follows: 6 as "atypical leiomyoma with limited experience", 7 as "smooth muscle tumor of low malignant potential", 2 as "atypical leiomyoma, low risk of recurrence," and 1 as "mitotically active leiomyoma, limited experience." Follow-up was 21 to 192 months (mean, 80.8 and median, 51.5). Only 2 tumors recurred, at 15 and 51 months, respectively; both were atypical leiomyoma with limited experience (multifocal moderate-to-severe atypia, no tumor cell necrosis, and mitotic counts of 4 and 5 mitotic figures /10 high-power fields, respectively). Both tumors had areas that were indistinguishable from benign leiomyoma and both had diffuse immunoreactivity for p16 and p53. Six other tumors that had focal staining for these markers all had a benign outcome. Both patients with recurrence were alive at last follow-up (at 40 and 74 mo). All the other patients were alive and disease-free.

Conclusions: This and other studies suggest that uterine tumors classified as STUMPs using criteria proposed by Stanford investigators are usually clinically benign but should be considered tumors of low malignant potential because they can occasionally recur, in some cases, years after hysterectomy. After a mean follow-up of 80.8 months, only 2 of 16 tumors in this study recurred. Both of the latter tumors fulfilled the criteria for atypical leiomyoma with limited experience. Notably, the 2 recurrent tumors were the only ones that were strongly immunoreactive for p16 and p53, supporting earlier observations that these markers may be helpful in the prediction of the behavior of STUMPs. Patients diagnosed with STUMPs should receive long-term surveillance.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / pathology
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Smooth Muscle Tumor / metabolism
  • Smooth Muscle Tumor / pathology*
  • Smooth Muscle Tumor / surgery
  • Tumor Suppressor Protein p53 / biosynthesis
  • Ubiquitin-Protein Ligases / biosynthesis
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*
  • Uterine Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases