Diffuse uterine leiomyomatosis is a benign condition with multiple poorly circumscribed smooth-muscle nodules occupying the myometrium in different proportions. Cellular leiomyoma is a variant of uterine leiomyoma presenting with increased smooth muscle cellularity with benign cytological features and architecture.
We report an unusual phenotypic variant of DUL spectrum disease manifesting as a large multilobulated cellular leiomyoma with retroperitoneal extension and minimal menstrual symptoms, posing significant diagnostic and intraoperative challenges. This case report was prepared in accordance with the CARE guidelines.

A nulliparous woman in her 40s presented with 6 months of insidious, dull-aching abdominal pain and three months of dyspepsia. She reported no menstrual complaints.

Over two months, she noted reduced appetite and a 6-kg weight loss. On examination, she appeared cachectic [body mass index (BMI) 18 kg/m²]. The abdomen was markedly distended by a term sized uterine mass arising from the pelvis (Figure 1). There was no clinical ascites.

Per-vaginal examination revealed the cervix pulled up behind the pubic symphysis with fullness in the posterior fornix. The uterus could not be felt separately. Per-rectal examination showed a firm anterior rectal wall bulge with free mucosa.

Laboratory parameters were normal except CA-125 Elevated at 276 U/mL. CA 19.9, Alpha Feto Protein (AFP), Lactate Dehydrogenase (LDH), and Carcinoembryonic Antigen (CEA) were within normal limits. Abdomino-pelvic magnetic resonance imaging (MRI) demonstrated a large ill-defined T2-isointense abdomino-pelvic mass measuring 26 × 16.5 × 17.5 cm, extending into extraperitoneal spaces. The cervix was not separately visualized. The lesion abutted major vessels posteriorly without clear invasion (Figure 2A and Figure 2B). No ascites or significant lymphadenopathy was noted. Given cachexia, rapid abdominal enlargement, and elevated CA-125, ovarian malignancy was considered. However, absence of ascites and lymphadenopathy lowered suspicion of advanced ovarian cancer. Imaging favored smooth-muscle pathology, but leiomyosarcoma could not be excluded. After counselling, exploratory laparotomy was planned with multidisciplinary backup.

Surgical Management and Postoperative Course

Through a midline vertical incision, a large multilobulated fleshy mass with multiple projections was identified. The lesion arose from an otherwise normal-appearing uterus (Figure 3) and extended into retroperitoneal and paravesical spaces. No peritoneal implants were seen. Frozen section analysis suggested a benign lesion. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Lymphadenectomy was not undertaken. A clear plane of cleavage was achieved in retroperitoneal areas. The right ureter was embedded within the mass and carefully dissected free. The specimen weighed 3.4 kg. One unit packed red blood cells was transfused intraoperatively.

Six hours postoperatively, she developed tachycardia and abdominal distension. Rapid deterioration prompted re-exploration. Approximately 1500 mL of clots were evacuated from the intra and retroperitoneal space. A 2-mm spurting retroperitoneal arterial bleeder was identified and secured. She received 4 units packed red blood cells, 4 units fresh frozen plasma, and 4 units cryoprecipitate. After intensive monitoring and supportive care, she recovered and was discharged on postoperative day 10.

Histopathology and Immunohistochemistry

On histopathological examination, microscopically, the tumor comprised oval elongated to spindle looking cells with bland nuclear features and tapered cytoplasmic ends. These cells were arranged in interlacing fascicles and in whorl pattern. At foci the tumor cells separated by edema and proteinaceous fluid, resulting in a trabecular, nested architecture.

Mitoses 2–3 per 10 HPF. Necrosis was absent. Spindle cell neoplasm with differentials including cellular leiomyoma and other malignant spindle cell neoplasms like malignant peripheral nerve sheath tumor (retroperitoneal origin) were considered and immunohistochemistry with Smooth Muscle Actin (SMA), S100 and Ki-67 proliferative index were done. Smooth Muscle Actin was diffusely positive in the tumor cells confirming the smooth muscle origin of the lesion favoring cellular leiomyoma. Ki-67 index was less than 5% ruling out malignancy, and S100 was negative ruling out neural origin in a retroperitoneal mass (Figure 4A, Figure 4B, Figure 4C). These findings supported a diagnosis of cellular leiomyoma within the spectrum of diffuse uterine leiomyomatosis.

Follow-up at six months and 1 year showed no recurrence clinically or on ultrasonography.

Diffuse uterine leiomyomatosis is an uncommon benign smooth-muscle disorder characterized by diffuse myometrial involvement. Classical presentation includes heavy menstrual bleeding and infertility. Our patient’s lack of menstrual symptoms and presence of constitutional symptoms made diagnosis challenging. The gross intraoperative appearance was unusual. Instead of diffuse uterine enlargement alone, a dominant multilobulated fleshy mass with extensive retroperitoneal extension was present, while the uterus appeared externally normal. This suggests a phenotypic variant within the DUL spectrum. Magnetic resonance imaging (MRI) is an important imaging tool in evaluation of soft tissue tumors of abdomen and pelvis and is preferred over computed tomography (CT) scan as it provides superior soft tissue contrast, identifies tissue composition and differentiates benign from malignant lesions. There may be alteration in signal characteristics when degenerative changes and cellular variants are noted [1],[2]. Intraoperative findings of, retroperitoneal extension and poor cervical delineation lead to suspicion of malignancy. Fibroids are well-defined, low T2 signal masses with homogeneous enhancement whereas irregular or ill-defined margins with heterogeneous T2 signals, high T1 signal for hemorrhage, restricted diffusion on DWI may raise suspicion of leiomyosarcoma [3]. Conclusive diagnosis is obtained only after histopathology and immunohistochemistry examination.

Management of DUL is individualized. Fertility-preserving approaches include modified myomectomy techniques and uterine artery occlusion strategies [4],[5],[6]. However, in extensive disease with retroperitoneal involvement, conservative surgery may be technically hazardous and hemorrhagic. In this patient, hysterectomy was appropriate given age, lack of fertility desire, disease extent, and intraoperative complexity. The postoperative hemorrhage underscores a key surgical lesson. Retroperitoneal dissection carries risk of concealed bleeding. Even after apparent hemostasis, small arterial bleeders may lead to significant hemoperitoneum. Vigilant monitoring, prompt recognition, and immediate re-exploration are lifesaving. Histopathological and immunohistochemistry examination for confirmation of diagnosis was critical to rule out malignancy and for follow-up.

Learning Points:

• Diagnostic overlap between benign and malignant smooth-muscle tumors.
• Importance of multidisciplinary surgical planning.
• Need for blood product preparedness.
• Role of histopathology in definitive diagnosis.
• Vigilance for concealed retroperitoneal bleeding.
• Postoperative hemorrhage in retroperitoneal dissections may present abruptly.

Our case highlights the challenges in diagnosis of a phenotypic variant of DUL. Among the three leiomyomatous conditions of uterus—cellular leiomyoma, diffuse uterine leiomyomatosis, and diffuse peritoneal leiomyomatosis, cellular leiomyoma can mimic sarcoma due to increased cellularity. Magnetic resonance imaging supported by histopathological and immunohistochemistry can facilitate the accurate diagnosis and aid in the customized management and follow up of atypical DUL spectrum immunohistochemistry can facilitate the accurate diagnosis and aid in the customized management and follow up of atypical DUL spectrum.