Uterine Leiomyomas With Bizarre Nuclei

Abstract

Leiomyoma with bizarre nuclei (LM-BN) is an uncommon tumor with histologic features (mononucleated or multinucleated bizarre cells that may have a diffuse distribution, prominent nucleoli, and karyorrhectic nuclei that may mimic atypical mitoses) that often causes confusion with leiomyosarcoma. Fifty-nine LM-BNs were collected from our consultation files over the years 2000 to 2011. Features recorded included patient age, therapy, tumor size, border, gross appearance, density and distribution of BN, mitotic count, karyorrhectic nuclei, prominent nucleoli, cells with conspicuous dense eosinophilic cytoplasm (rhabdoid-like), vascular changes and type of vasculature, and presence of necrosis and its nature. Follow-up information was obtained for all patients. Patients ranged in age from 25 to 75 (average 45) years (11 patients between 25 and 35 y, 20 between 36 and 45 y, 22 between 46 and 55 y, and 6 between 56 and 75 y). Forty-two underwent hysterectomy and 17 myomectomy. For 51 tumors gross findings were known. Forty (78%) had a solid white and whorled cut surface and 11 (22%) a yellow appearance. Five (10%) neoplasms showed prominent cystic degeneration, and hemorrhage and/or necrosis was seen in 9 (18%). Forty-five LM-BNs had a pushing margin with the surrounding myometrium, whereas 1 showed irregular borders. Margins could not be ascertained in the slides available in 13 cases. Twenty-eight (48%), 19 (32%), and 12 (20%) LM-BN showed low, intermediate, and high BN density. Eighteen (30%) tumors showed diffuse, 26 (44%) showed multifocal, and 15 (26%) had focal BN distribution. Mitotic counts ranged from 0 to 7/10 high-power fields (HPF) (average 1 to 2/10 HPF). Thirty-seven (63%) had <2/10 HPF, 19 (32%) had 2 to 5 mitoses/10 HPF, and in 3 tumors (5%) mitotic counts were 6, 7, and 7/10 HPF (2 with focal and 1 with diffuse BN). All but 4 LM-BNs showed karyorrhectic nuclei, striking in 12 neoplasms, mimicking atypical mitoses. Nineteen (32%) LMs had prominent eosinophilic nucleoli surrounded by a clear halo. Ischemic necrosis was detected in 21 (36%) LM-BN. Rhabdoid-like cells were noted in 24 (41%) tumors. All patients had no evidence of recurrence, ranging from 1 to 13 years (overall average 6 y; in patients with myomectomy 6.3 y with a range of 2.6 to 11 y). Our results corroborate that LM-BN is associated with a favorable outcome even in those patients only treated by myomectomy and highlights that a conservative approach can be undertaken in these patients, as many of them are of reproductive age. Because of the favorable outcome, the term LM-BN is preferable to alternative terminology including "atypical leiomyoma."

Two Subtypes of Atypical Leiomyoma

“…Past studies have shown variable Ki-67 percentages among ALM cases, ranging from 0 to 30% (3, 4). Our study showed similar variability, although most cases had low proliferation rates.…”

“…Croce et al (4) provided a comprehensive evaluation of histologic features in their study of 59 ALM cases where they analyzed features including cellularity, density of nuclear atypia, mitotic count, presence of prominent nucleoli, karyorrhectic nuclei, pseudonuclear inclusions, rhabdoid-like cells, vascular changes, eosinophilic hyaline globules, and ischemic necrosis. In this study, they found that 18 cases showed diffuse atypia, 26 showed multifocal atypia and 15 showed focal atypia.…”

“…When combined with the other four studies (1, 2, 4, 11), a total of 250 ALM cases have reported clinical and histologic features (Table 4). Overall 50% of cases showed a diffuse distribution of nuclear atypia, while 16.5% of cases had only focal atypia and 33.5% had multifocal areas with atypia.…”

“…Overall 50% of cases showed a diffuse distribution of nuclear atypia, while 16.5% of cases had only focal atypia and 33.5% had multifocal areas with atypia. Others have postulated that diffuse cytologic atypia in ALM may be considered a potential risk factor for recurrence and malignant potential (1, 4). The clinical and histologic parameters among these studies (Table 4) show that ALM presents in middle age (mean age of 40–45 years old) with a relatively large tumor size (6.8–7.6 cm) and with a low rate of recurrence (2–7%).…”

“…Of particular clinical concern is the fact that some of the histologic features of ALM mimic those of LMS and may lead to misdiagnosis. Two previous large studies found that 17 to 27% of ALM and other benign variants of uterine smooth muscle tumors were misinterpreted as LMS (4, 6). Recent studies that have focused on the molecular genetics of these tumors have also begun to raise the question whether ALM is a single disease or multiple distinct entities (4, 5).…”