When Pathology Changes Three Times and Pulmonary Embolism Strikes: How MDT Achieves a Pathologic Complete Response in Dual Primary Gynecologic Cancer

BEIJING — In this extraordinary case — the third volume of Arion's "Case Breakthrough Notes" (破局手记) series — a 68-year-old woman presented with postmenopausal vaginal bleeding lasting four years. What followed was a diagnostic odyssey spanning three distinct pathology reports, a life-threatening pulmonary embolism, and ultimately, a pathologic complete response (pCR) achieved through the power of multidisciplinary collaboration and precision medicine.

The Case: A Diagnostic Maze

The patient, a 68-year-old woman, was initially evaluated at an outside hospital where cervical cancer was suspected. However, a biopsy at Beijing Arion Cancer Hospital revealed a different diagnosis entirely: undifferentiated sarcoma of the ovary. Genetic testing then uncovered a critical finding — MSH6 germline mutation with MSI-H (microsatellite instability-high) and TMB-H (tumor mutational burden-high) status, with a PD-L1 CPS of 5, strongly suggesting potential benefit from immunotherapy.

The tumor markers painted a concerning picture: CA-125 at 204 U/mL and HE4 at 205 pmol/L. PET/CT imaging confirmed advanced disease with a hypermetabolic mass in the uterus and left adnexa, accompanied by multiple hypermetabolic lymph nodes in the retroperitoneum and pelvis.

The Three Pathology Shifts

First diagnosis (June 19, 2024): Cervical biopsy indicated an epithelial-derived tumor favoring adenocarcinoma, NOS. Immunohistochemistry showed PAX-8 (+), ER (moderately +, 10%), PR (-), P53 (+, 90%), Ki-67 (+, ~35%).

Second diagnosis (June 21, 2024): Pelvic mass biopsy revealed a malignant tumor with extensive necrosis, consistent with undifferentiated sarcoma on immunohistochemistry — confirmed by both Arion's pathology department and Peking Union Medical College Hospital (PUMCH) consultation.

Final diagnosis (October 22, 2024, post-surgery): Definitive pathology confirmed dual primary cancers:

• Endometrial clear cell carcinoma — primary uterine tumor showing only mild treatment response (TRG Grade 3)
• Undifferentiated ovarian sarcoma — achieving pathologic complete response (pCR, TRG Grade 1) with extensive necrosis and inflammatory infiltration, no viable tumor cells identified in the ovary

Lymph nodes: 0/35 positive — a remarkable finding in advanced-stage disease. This striking heterogeneity in treatment response between the two primary tumors, confirmed by PUMCH consultation, underscored the fundamental importance of pathology in guiding gynecologic oncology treatment.

Treatment Journey: From Neoadjuvant to Surgery

The MDT team — comprising Gynecologic Oncology, Pathology, Diagnostic Radiology, Medical Oncology, Vascular Interventional Radiology, and Critical Care — convened to develop a comprehensive strategy.

Neoadjuvant therapy (July–October 2024): Based on the MSI-H/TMB-H molecular profile, the team initiated a novel approach combining immunotherapy with chemotherapy. The regimen included paclitaxel + carboplatin + pembrolizumab + bevacizumab. However, after the first cycle, the patient developed a carboplatin allergy, prompting an immediate switch to cisplatin (TP regimen) from the third cycle onward. Five cycles of neoadjuvant therapy were completed, with the final cycle omitting bevacizumab to prepare for surgery.

The tumor marker response was dramatic: CA-125 fell from 279.6 U/mL to 11.3 U/mL. PET/CT confirmed significant tumor shrinkage and reduced metabolic activity, providing clear evidence of treatment efficacy.

Radical surgery (October 22, 2024): The patient underwent comprehensive cytoreductive surgery including radical hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and appendectomy. The procedure achieved satisfactory tumor debulking.

The Crisis: Pulmonary Embolism

In January 2025, the patient was emergently admitted with generalized weakness and limited mobility of the right lower extremity. Imaging confirmed pulmonary embolism. The MDT team immediately activated a crisis response protocol:

• Low molecular weight heparin anticoagulation initiated
• Prophylactic inferior vena cava (IVC) filter placement on January 10, 2025
• Anticancer therapy adjusted to albumin-bound paclitaxel — a lower bleeding-risk chemotherapy agent

Under Prof. Wu Ming's guidance from PUMCH, the patient completed three additional cycles of albumin-bound paclitaxel + pembrolizumab. CA-125 normalized to <5 U/mL.

Maintenance and Long-Term Follow-Up

Since April 23, 2025, the patient has been receiving pembrolizumab monotherapy (200 mg every 3 weeks) as maintenance treatment. The results have been remarkable:

• CA-125 consistently normal (3–5 U/mL)
• CT scans in July, October, and December 2025, and February 2026: no evidence of tumor recurrence
• Progression-free survival (PFS): exceeding 19 months from initial diagnosis
• Quality of life: excellent, with normal daily activities

Mildly enlarged abdominal lymph nodes observed on imaging are considered post-treatment changes or mesenteric panniculitis rather than metastatic disease.

Expert Commentary: Prof. Wu Ming, Peking Union Medical College Hospital

"This is an exceptionally instructive case that demonstrates the fundamental importance of pathology as the cornerstone of precision treatment, and the irreplaceable value of multidisciplinary collaboration in managing complex clinical scenarios."

"The patient presented with conflicting pathology from two biopsy sites — cervical biopsy favoring adenocarcinoma, pelvic mass biopsy suggesting undifferentiated sarcoma. The critical first decision was to re-examine all slides and re-biopsy, which laid the foundation for subsequent precision treatment."

"This is a case of dual primary cancers: endometrial clear cell carcinoma and undifferentiated ovarian sarcoma. Postoperative pathology showed that the ovarian undifferentiated sarcoma achieved pCR (TRG Grade 1), while the endometrial clear cell carcinoma showed only mild treatment response (TRG Grade 3). This striking heterogeneity in treatment response confirms that the two lesions have different tissue origins and different sensitivities to immunotherapy combined with chemotherapy — underscoring the foundational role of pathology and genetic testing in gynecologic oncology."

"Treatment strategy-wise, this case broke with convention. Although neoadjuvant therapy for ovarian cancer typically uses chemotherapy ± bevacizumab, immunotherapy is not a first-line choice. However, based on the MSI-H/MSH6 germline mutation molecular profile, we decisively added PD-1 inhibitor to the standard regimen. The result — CA-125 dropping from 279.6 to 11.3 U/mL, PET-CT showing significant metabolic reduction, and postoperative pCR of the ovarian undifferentiated sarcoma — proves that immunotherapy played a key role, and the molecular profile guided this decision."

"Regarding postoperative adjuvant therapy duration, there is currently no high-level evidence to guide treatment cycles for MSI-H gynecologic tumors after neoadjuvant therapy. Based on the excellent prognosis — pCR of the ovarian lesion and 0/35 negative lymph nodes — combined with the patient's sustained sensitivity to immunotherapy, we decided to complete adjuvant chemotherapy and transition to pembrolizumab monotherapy maintenance. The subsequent sustained remission for over 10 months confirms the rationality of this approach."

"The sudden pulmonary embolism during treatment required rapid MDT response: anticoagulation + IVC filter + chemotherapy adjustment. We balanced thrombosis risk with treatment continuation, switching to albumin-bound pacrolizumab to minimize bleeding risk while maintaining anticancer efficacy. The patient now has PFS exceeding 19 months with excellent quality of life."

"This case teaches us: with precision pathology as the foundation, molecular profiling as the guide, and MDT collaboration as the safeguard — even when facing dual primary cancers, evolving pathology, advanced stage, and multiple complications — we can still achieve long-term, high-quality survival for patients."

— Prof. Wu Ming, Peking Union Medical College Hospital, Department of Obstetrics & Gynecology

Key Clinical Insights

1. Pathological diagnosis is the cornerstone of precision treatment. This case demonstrates the complexity of gynecologic tumor pathology, where multiple biopsy sites may yield different diagnoses. When pathological types are inconsistent, clinicians must be vigilant for the possibility of multiple primary cancers.
2. MSI-H/TMB-H is a pan-cancer biomarker for immunotherapy efficacy. Even in rare pathological types, patients with MSI-H status may achieve significant benefit from immunotherapy — including pathologic complete response of metastatic lesions.
3. Treatment complications require MDT rapid response. The pulmonary embolism was managed through multidisciplinary collaboration, with individualized risk control and treatment continuation strategies rather than simply abandoning anticancer therapy.

About the Case Breakthrough Notes Series

"Case Breakthrough Notes" (破局手记) is Arion Cancer Hospital's flagship clinical case series, documenting complex cancer cases where multidisciplinary collaboration achieved breakthroughs beyond standard treatment protocols. The series is guided by:

• Prof. Sun Min — Honorary Editor-in-Chief, UPMC Hillman Cancer Center
• Prof. Ma Zhiqiang — Honorary Editor-in-Chief, Arion Cancer Hospital GI Oncology Center
• Prof. Bai Li — Honorary Editor-in-Chief, Senior Oncology Expert

Column Editor: Prof. Gao Xiaofang

Contributing Author: Prof. Li Ya

Expert Commentary: Prof. Wu Ming, Peking Union Medical College Hospital