Leiomyoma with nuclear atypia: Rare diseases that present a common diagnostic problem

Abstract

Leiomyoma with nuclear atypia describes a group of uterine smooth muscle tumors with a wide range of histologic and clinical presentations and remarkable nuclear atypia. These include fumarate hydratase-deficient leiomyoma (FH-LM), intravenous leiomyomatosis (IV-LM), and leiomyoma with bizarre nuclei (LM-BN). Other uterine mesenchymal tumors, such as perivascular epithelioid tumor (PEComa) and inflammatory myofibroblastic tumors (IMFT) are the mimickers of leiomyoma with nuclear atypia. LM-BN is the primary tumor model with a long history in gynecologic pathology, but the histogenesis of LM-BN remains largely unknown. Differentiating LM-BN from other benign variants, tumors with uncertain malignant potential (STUMP), or fully malignant leiomyosarcoma (LMS) can be diagnostically challenging. Recent progress has improved the diagnosis of many types of leiomyoma with nuclear atypia based on their specific histology and molecular alterations. LM-BN is now a diagnosis of exclusion. In this article, I review the history of leiomyoma with nuclear atypia and compare the clinical, histologic, and molecular features of LM-BN with those of its mimics. In particular, I highlight the current progress made in molecular genetics and pitfalls in the diagnosis of different myogenic tumors with nuclear atypia.

Keywords: Fumarate hydratase-deficient leiomyoma; Gene mutation; IMFT, Leiomyosarcoma, STUMP; Intravenous leiomyomatosis; Leiomyoma with bizarre nuclei; Leiomyosarcoma; Nuclear atypia; PEComa.

Figure 1

Photomacrographs of leiomyoma with bizarre nuclei in 4 examples.

Figure 2

Photomicrographs of leiomyoma with bizarre nuclei.

Figure 3

Intermediate power view of leiomyoma with bizarre nuclei shows area of usual type leiomyoma (right low corner).

Figure 4

Intermediate power view of leiomyoma with bizarre nuclei shows low (A), intermediate (B) and high (C) density of nuclear atypia.

Figure 5

Leiomyoma with bizarre nuclei and atypical mitosis (arrowhead).

Figure 6

Leiomyoma with fumarate hydratase alteration. A. Low power field shows dilated and staghorn like vessels; B. intermediate power field demonstrates tumor cell arrangement similar to peripheral nerve sheath tumor.

Figure 7

High power view of nuclear features of leiomyoma with fumarate hydratase alteration.

Figure 8

Immunohistochemistry analysis of 2SC (B) and FH (C) in leiomyoma with fumarate hydratase alteration.

Figure 9

Intravenous leiomyomatosis (A) with areas of nuclear atypia (B).

Figure 10

Inflammatory myofibroblastic tumor (A) with areas of nuclear atypia (B).

Figure 11

Perivascular epithelioid tumor (PEComa) of epithelioid (A) and spindle cell (B) variants with nuclear atypia.