Postoperative management challenges in concurrent endometrioid carcinoma and PEComa a case report.

This case study involves a 38-year-old female with a decade-long history of endometrial thickening, initially detected by ultrasound examination revealing an endometrial thickness of 20 mm. Despite receiving intermittent treatment with oral progesterone (40 mg daily for 10 consecutive days during the luteal phase of her menstrual cycle) and short-acting oral contraceptives (Drospirenone and Ethinyl Estradiol Tablets II, 1 tablet daily, administered 1–2 times per month), her symptoms persisted. Notably, she underwent only one ultrasound examination during this period and did not receive any invasive diagnostic procedures such as diagnostic curettage, endometrial biopsy, or hysteroscopy. Over the past four months, she experienced intermittent vaginal bleeding with a gradual increase in blood volume. Subsequent to a hysteroscopy and endometrial biopsy conducted at a different healthcare facility, she was diagnosed with endometrial cancer. Her medical and family history are non-contributory, and comprehensive physical and gynecological examinations did not reveal any remarkable findings. The patient has no history of exogenous estrogen intake.General Information: BMI is 18.73 kg/m² (within normal range).Obstetric and Gynecological History: The patient is married but has no reproductive history, has never been pregnant, and has no delivery history.Previous Examination History: Apart from the ultrasound examination reported 10 years ago, the patient had not undergone any other gynecological ultrasound examinations previously.Related Medical History: The patient has no history of polycystic ovary syndrome (PCOS) diagnosis and has never received treatment for infertility. Upon scrutiny of tumor markers, the CA125 and HE4 levels of the patients before the operation were all within the normal range. Subsequent ultrasonic examination yielded a depiction of a uterus with normal dimensions, featuring an endometrium lining of 6 mm in thickness. Notwithstanding, the uterine cavity was found to harbor anechoic regions complemented by echogenic foci, collectively 13.4 mm, indicating the presence of fluid accumulation. Additionally, a hypoechoic tumor measuring 22* 19* 13 mm was detected within the posterior wall of the myometrium. The ultrasound examination did not reveal any abnormal tumor borders or signs of aggressive behavior, leading to an initial misdiagnosis of the PECOMA lesion as a common uterine fibroid. Comprehensive abdominal CT scans yielded several pertinent revelations. The uterus exhibited a consistent volume, devoid of any notable enlargement, while the bilateral ovaries remained unaltered, free from abnormal density shadows. Furthermore, the pelvic structures including muscles and ligaments displayed a normal morphological pattern and trajectory, with no appreciable thickening of the intestinal wall. Of particular note were the multiple small lymph nodes detected bilaterally in the inguinal region and pelvic cavity, along with two enlarged lymph nodes discerned on the right side of the pelvis, measuring approximately 1.5 cm*1.0 cm. Additionally, a modest volume of fluid was also observed within the pelvic cavity. Notably, the small myometrial tumor was not visible on the CT scan, indicating that it was small and difficult to detect. Transverse MRI imaging of the pelvis reveals a notable lymph node in the right iliac vascular region, as indicated by the red arrow (Fig.  1 A-B). The lymph node measures approximately 1.4 cm × 0.9 cm, with distinct contrast enhancement, suggesting possible pathological changes. Sagittal MRI imaging shows another enlarged lymph node in the right iliac vascular region, marked by the red arrow. This lymph node measures approximately 1.5 cm × 1.0 cm and also demonstrates significant enhancement, indicating the presence of a possible lesion in this area. These imaging results suggest that the enlarged lymph nodes in the pelvic region may indicate metastatic disease or other pathological processes, requiring further diagnosis and evaluation. Fig. 1 MRI findings of lymph nodes in the pelvic region. A . Transverse imaging revealed a notable lymph node in the right iliac vascular region of the pelvis, measuring approximately 1.4 cm x 0.9 cm, with distinct evidence of enhancement. B . Sagittal imaging revealed a notable lymph node in the right iliac vascular region of the pelvis, measuring approximately 1.5 cm x 1.0 cm MRI findings of lymph nodes in the pelvic region. A . Transverse imaging revealed a notable lymph node in the right iliac vascular region of the pelvis, measuring approximately 1.4 cm x 0.9 cm, with distinct evidence of enhancement. B . Sagittal imaging revealed a notable lymph node in the right iliac vascular region of the pelvis, measuring approximately 1.5 cm x 1.0 cm In terms of molecular typing, detailed molecular analysis pinpointed specific mutations associated with the patient’s endometrial cancer subtype, identified as NSMP type. Mutations were identified in CTNNB1, including G34R and S33Y, as well as in FGFR2 (C382R), DICER1 (E1705K), PIK3R1 (F456 Q457del), CTCF (S130), ARID1A (R1528), and KRAS (G12R), were detected. Conversely, no mutations were detected in TSC1/TSC2, TFE3 fusion, and RAD51B gene rearrangement. The patient’s decision to forego fertility-preserving treatment modalities necessitated the conduct of laparoscopic total hysterectomy, bilateral salpingectomy, and sentinel lymph node biopsy. Intraoperatively, the uterus was exhibited to possess a normal size and a smooth surface, while bilateral ovaries and fallopian tubes appeared structurally unremarkable. Importantly, no abnormal lesions were detected on the liver, bile ducts, spleen, stomach, appendix, diaphragm, pelvic cavity, or intestinal serosa, and no signs of involvement of the rectum or bladder.The right sentinel lymph node, located proximate to the common iliac artery, measured 1*1.5*1 cm and 1*1*1 cm, displaying a fusion-like appearance. Conversely, the left visualized lymph node did not demonstrate significant swelling. In order to rule out lymph node metastasis of endometrial cancer, we conducted intraoperative frozen section pathological examination. Frozen section: Left sentinel lymph node: Fatty tissue measuring 2.5 × 1.5 × 0.8 cm, gray-red and pale yellow in color, soft in texture. No obvious lymph nodes were seen grossly.Right sentinel lymph node: One lymph node was identified, with indistinct margins and dumbbell shape, measuring 2.5 × 1.8 × 1.0 cm. After the operation, we conducted a detailed pathological examination.Postoperative specimen: Total hysterectomy with bilateral fallopian tubes: The uterus measured 8 × 6.5 × 4 cm, with a distance of 7 cm from the fundus to the external os. The myometrial thickness was 1.5–2.2 cm. The endometrial cavity was filled with cauliflower-like masses, measuring 4 × 3.3 × 0.2 cm. The section did not grossly involve the myometrium, and the lower margin did not reach the internal cervical os. A nodule was seen in the myometrium, with the largest diameter of 0.7 cm, dark red in color. The cervix showed mild erosion. The uterine serosa was smooth. One fallopian tube measured 7 cm in length, with the fimbria visible and a diameter of 0.4 cm; the other fallopian tube measured 5 cm in length, with the fimbria visible and a diameter of 0.4 cm. Pathological Diagnosis: Low-grade (well-differentiated) endometrioid carcinoma of the uterus, just involving the myometrium, with the lower margin not reaching the internal cervical os. No vascular or lymphatic invasion or neural invasion was identified. Immunohistochemical results (2400765-7): ER ( + + to +++), PR ( + + to +++), P53 (wild-type expression), MLH1 (+), PMS2 (+), MSH2 (+), MSH6 (+).A nodule was seen in the uterine wall, with spindle cell proliferation. The vessels were rich, and the tumor cells were distributed around the vessels. Most of the tumor cells were spindle-shaped, with some having abundant cytoplasm and an epithelioid appearance. No tumor cell necrosis was seen. No obvious nuclear atypia or pleomorphism was present, and mitotic figures were rare. PEComa was considered based on immunohistochemical results. Immunohistochemical results (2400765-19): ER (+), PR (+), CD34 (vascular endothelium+), D2-40 (lymphatic endothelium+), desmin (+), SMA (+), caldesmon (+), HMB-45 (+), Melan-A (−), S-100 (−), Ki-67 (+, approximately 2%); chronic cervicitis; no significant changes in bilateral fallopian tubes. Frozen section of the left sentinel lymph node: Two lymph nodes were examined, with no definite metastatic carcinoma identified. Nodule in the right sentinel lymph node site: The vessels were rich, and the tumor cells were distributed around the vessels. Most of the tumor cells were spindle-shaped, with some having abundant cytoplasm and an epithelioid appearance. No tumor cell necrosis was seen. No obvious nuclear atypia or pleomorphism was present, and mitotic figures were rare. PEComa was considered based on immunohistochemical results. Immunohistochemical results (2400765-4): ER (+), PR (+), CD34 (vascular endothelium+), D2-40 (lymphatic endothelium+), desmin (+), SMA (+), caldesmon (+), HMB-45 (+), Melan-A (−), S-100 (−), Ki-67 (+, approximately 2%) Figs. 2 and 3 . Fig. 2 Pathology of Endometrioid Carcinoma. A : Endometrioid carcinoma HE staining 40X. The cancer cell nuclei are stained dark purple. B : Endometrioid carcinoma HE staining 200X. Destruction of glandular structures is observed, with variable sizes. Cancer cell nuclei are large and darkly stained, with pathological mitotic figures visible. C : wild-type P53 expression 20X. D : ER++~+++ 20X. E : PR++~+++ 20X. F : MLH1 + 20X. G: MSH2 + 20X. H: MSH6 + 20X. I: PMS2 + 20X Pathology of Endometrioid Carcinoma. A : Endometrioid carcinoma HE staining 40X. The cancer cell nuclei are stained dark purple. B : Endometrioid carcinoma HE staining 200X. Destruction of glandular structures is observed, with variable sizes. Cancer cell nuclei are large and darkly stained, with pathological mitotic figures visible. C : wild-type P53 expression 20X. D : ER++~+++ 20X. E : PR++~+++ 20X. F : MLH1 + 20X. G: MSH2 + 20X. H: MSH6 + 20X. I: PMS2 + 20X Fig. 3 Preoperative Uterine Myometrial Nodule Image and Postoperative Pathology. A : Uterine myometrial nodule HE staining 40X. Abundant vascular distribution is observed. B : Uterine myometrial nodule HE staining 200X. Spindle cell proliferation is visible, with spindle cells arranged concentrically or radially around the blood vessels. C : SMA+ 100X. D : HMB45 + 100X. E : Melan-A- 100X Preoperative Uterine Myometrial Nodule Image and Postoperative Pathology. A : Uterine myometrial nodule HE staining 40X. Abundant vascular distribution is observed. B : Uterine myometrial nodule HE staining 200X. Spindle cell proliferation is visible, with spindle cells arranged concentrically or radially around the blood vessels. C : SMA+ 100X. D : HMB45 + 100X. E : Melan-A- 100X Considering the integration of these observations with immunohistochemical staining results, a preliminary diagnosis of with stage IA endometrial cancer, along with perivascular epithelioid cell tumor (PEComa) was entertained. The postoperative diagnosis affirmed the patient’s condition as stage IA endometrial cancer and concurrent PEComa. We fully explained the condition and the insufficiency of the surgery to the patient, who indicated understanding and refused additional surgical treatment.Given the rarity of PEComa and the ambiguity surrounding its its malignant potential, the patient was advised to undergo PET-CT to exclude the presence of PEComa lesions elsewhere in the body, and to initiate rigorous postoperative surveillance. As of the current follow-up period of nine months, the patient did not receive any oral medication treatment, and the patient has demonstrated no evidence of recurrence or metastasis. The recommendation for PETCT examination and close follow-up is predicated on the possibility that PEComa tumors may persist in other organs within the body.

The four cases of uterine PEComa detailed above present various clinical and pathological features. Each case involved a combination of PEComa with different types of endometrial carcinoma, demonstrating the complexity and rarity of these coexisting conditions. Preoperative imaging often indicated uterine fibroids, but postoperative pathological analysis confirmed PEComa. Immunohistochemical markers varied among cases, emphasizing the necessity of comprehensive diagnostic evaluations. Case 1 highlighted the malignant potential of PEComa with extensive metastasis [ 11 ], while Case 2 and Case 3 showed the occurrence of PEComa with ovarian metastases and serous adenocarcinoma [ 4 , 12 ], respectively. Case 4 involved tuberous sclerosis, adding another layer of complexity to the patient’s condition [ 13 ] These cases underscore the importance of meticulous diagnostic procedures and the challenges in managing such rare and concurrent pathologies. Further research and case studies are essential to enhance our understanding of the pathophysiology and to develop targeted therapeutic strategies for PEComa, particularly when it coexists with other malignancies Table 1 . Table 1 Review of previous literature Number Age Diagnosis Location Imaging indicators Positive markers References 1 67 Malignant uterine PEComa infiltrating myometrium leiomyoma, well-differentiated endometrial cancer and multiple hepatic metastasis myometrium Uterine fibroids HMB-45 + Melan-A+ PMID: 27,452,081 CD10- TFE3 + 2 60 PEComa of the uterus with bilateral ovaries transfer of well-differentiated endometrial adenocarcinoma myometrium Uterine fibroids CD68+ PMID: 15,369,963 CD117- CD10+- 3 25 PEComa of the uterus with Endometrial serous adenocarcinoma myometrium Uterine fibroids HMB45(+) PMID: 30,317,387 Vimentin (++) SMA(+++) Caldesmon(+++) 4 45 PEComa of the uterus with endometrial cancer and tuberous sclerosis myometrium Uterine fibroids ER+ PMID: 37,621,679 PR+ P53mutation TSC2 mutation Review of previous literature

In this case report, a 38-year-old female patient was admitted to the hospital with a history of prolonged endometrial thickening and recent onset of persistent vaginal bleeding, ultimately diagnosed with concurrent endometrioid carcinoma and PEComa. PEComa (perivascular epithelioid cell tumor) is a rare soft tissue tumor, especially in gynecology [ 4 , 5 , 7 , 14 ]. Most patients with PEComa exhibit non-specific symptoms, with clinical manifestations varying according to the location of the tumor, such as abnormal uterine bleeding, pelvic and abdominal pain, etc [ 15 , 16 ]. In exceptional cases, patients may present with abdominal bleeding or vaginal mass discharge [ 9 , 17 , 18 ]. In the literature, PEComa of the uterus is mostly located within the muscle wall, usually solitary, with multiple nodules being uncommon. Some cases may be associated with cystic degeneration [ 19 ]. Contrasting with published cases, the distinguishing feature of the current case is the combination of endometrioid carcinoma and PEComa. Shan et al. reported a case of endometrial serous carcinoma stage IB concomitant with PEComa [ 4 ]. The patient underwent comprehensive staging for endometrial cancer, including pelvic and common iliac lymph node dissection, followed by postoperative chemotherapy, and exhibited no signs of recurrence or metastasis at 22 months of follow-up. In contrast, the present case involved sentinel lymph node biopsy alone, without subsequent chemotherapy. Currently, the therapeutic approach for PEComa remains undetermined. The etiology of PEComa is related to TSC gene mutations, which result in increased TSC1/TSC2 activation and cell proliferation [ 4 , 20 – 22 ]. PEComa development is closely linked to the constitutive activation of the mTOR pathway. TSC1 and TSC2 genes encode proteins that negatively regulate mTOR complex 1. TSC1/2 gene inactivation can cause excessive mTOR pathway activation. In cases where TSC1/2 gene mutation or inactivation is not detected, the activation of the mTOR pathway may be triggered by other mechanisms, such as gene fusion or abnormal gene expression. However, treatment with mTOR inhibitors can still be considered [ 23 – 25 ]. The activation of the mTOR pathway may be triggered by other mechanisms, such as gene fusion or abnormal gene expression. However, treatment with mTOR inhibitors can still be considered. In some PEComa cases, molecular alterations like TFE3 gene fusion or FLCN gene mutation may be present, while genes such as VHL and MET show no mutations. This can further clarify the molecular subtypes of PEComa and provide evidence for individualized treatment [ 26 ]. This finding provides clues for future research toward targeted therapeutic strategies targeting the mTOR pathway [ 27 ].With respect to the biological behavior of PEComa, Folpe et al. [ 28 ]. have proposed criteria for classifying PEComa into benign, indeterminate malignant potential, and malignant, with this case falling into the indeterminate category. Consequently, future treatment and follow-up strategies should be tailored to this uncertainty. An important aspect of this case is understanding the molecular mechanisms that could link the two coexisting tumors—endometrioid carcinoma and PEComa. While both neoplasms have distinct histopathological features, there are potential overlapping molecular pathways that may drive their coexistence. One such pathway is the PI3K/AKT/mTOR signaling axis, which has been shown to play a role in both endometrioid carcinoma and PEComa. For instance, mutations in the PTEN gene, a common event in endometrial carcinoma, may also be a factor in the development of PEComa [ 29 – 32 ]. In addition, ARID1A mutations, frequently found in endometrial carcinoma, may have a role in driving both tumor types when coexisting in a single patient. Expanding the genetic landscape of endometrial carcinoma could provide further insights into the co-occurrence of these two rare tumors. Endometrial carcinoma is characterized by mutations in PTEN, ARID1A, and the PI3K/AKT/mTOR pathway [ 29 – 32 ]. These genetic alterations may predispose to the formation of PEComa, especially in the context of endometriosis, offering a potential explanation for the collision of these two tumors. The shared genetic pathways highlight the importance of targeted therapies that may address both tumor types, improving treatment outcomes. In conclusion, the occurrence of PEComa with endometrioid carcinoma represents an exceptionally rare clinical presentation, necessitating an individualized approach to therapeutic intervention and subsequent monitoring for patients. Given the numerous challenges encountered in diagnosing and treating PEComa, there exists an urgent requirement for further scientific inquiry aimed at enhance our understanding of the pathophysiological mechanisms, how to distinguish with leiomyoma on imagingas, well as exploring more effective therapeutic methodologies. Simultaneously, raising awareness about this case is of paramount importance in enhancing the prognostic outlook for patients suffering from this uncommon disorder.

Endometrioid carcinoma, a neoplasm originating from the endometrium, represents one of the most common malignancies in gynecology. Its occurrence is known to escalate with advancing age, especially among post-menopausal women, with the majority exhibiting a favorable prognosis. It is often coexists with the leiomyoma of the uterine, ovarian neoplasms, or may manifest independently. Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor comprising perivascular epithelioid cells that exhibit immunohistochemical markers characteristic of both melanocytic and smooth muscle cell differentiation [ 1 – 3 ]. Pecomas localized within the female reproductive tract account for more than 1/4 of all reported PEComas, with approximately 70% occurring in the corpus uteri [ 4 , 5 ], Isolated cases of PEComas have also been reported in the cervix [ 6 – 8 ], vagina/vulva [ 7 ], and broad or round ligament [ 9 , 10 ] .The age of the affected individuals range from 40 to 50, whereas the median age for PEComa in the vagina, vulva, and broad ligament is reported to be 28, 20 and 25, respectively [ 7 ]. PEComa is a rare tumor, most of which is malignant or an indeterminate potential for malignancy. There is a paucity of literature reporting on its solitary presentation or its concurrent with other tumors. The co-occurrence of endometrioid carcinoma and PEComa within the same patient is extremely rare. Such rarity presents not only a diagnostic challenge but also complicating treatment selection and prognosis evaluation. This study is designed to report a case post-surgery of concurrent endometrioid carcinoma combined with PEComa, a scenario that is not only rare but also poses significant diagnostic challenges. This article provides a detailed account of the clinical presentation, diagnostic process, treatment, and follow-up outcomes, offering insights for the management of this uncommon complication. It emphasizes the importance of accurate diagnosis and individualized treatment strategies. Additionally, this case report offers clinical data for future investigative efforts and facilitates deeper understanding and discussion on this rare disease association.