Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.

BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Prognostic analysis of peritoneal washing cytology during interval debulking surgery in advanced ovarian cancer.

BACKGROUND: Interval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytology (PWC) has been identified as a prognostic factor, its comprehensive assessment during IDS remains unexplored. Therefore, we aimed to evaluate PWC efficacy during IDS, alongside other factors including residual disease and the modeled cancer antigen 125 (CA-125) ELIMination rate constant K (KELIM), by retrospectively reviewing the medical records of 25 patients with advanced ovarian cancer underwent neoadjuvant chemotherapy and IDS between January 2017 to June 2023. RESULTS: Twelve (48.0%) patients were PWC-positive, and the remainder were PWC-negative. PWC was performed at laparotomy during IDS, after which five (41.7%) PWC-positive and four (30.8%) PWC-negative patients received bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, for maintenance treatment. Four (33.3%) PWC-positive and 10 (76.9%) PWC-negative patients received poly adenosine diphosphate (ADP)-ribose polymerase inhibitors. In patients who received bevacizumab and poly ADP-ribose polymerase inhibitors, overall survival and progression-free survival did not significantly differ between those who were PWC-positive and PWC-negative (p = 0.27 and 0.20, respectively). Progression-free survival significantly differed between those with favorable and unfavorable CA-125 KELIM (p = 0.02). Multivariate analysis indicated that optimal surgery and favorable CA-125 KELIM were associated with better progression-free survival (p < 0.01 and 0.02, respectively), with only optimal surgery associated with better overall survival (p = 0.04). CONCLUSIONS: A positive PWC at IDS was not associated with survival in advanced ovarian cancer. Our findings indicate that although PWC status at IDS should be one of the factors determining survival in patients with advanced ovarian cancer, recent improvements in maintenance therapy may make the combination of CA-125 KELIM and PWC status a more useful prognostic factor in selecting treatment after IDS. Further studies are needed to validate these results, highlighting the potential importance of maintenance treatment after IDS and the need for further research to validate the clinical significance of a positive PWC.

Endoscopic Endonasal Transsphenoidal Surgery for Intrasellar Mixed Germ Cell Tumors.

A mixed germ cell tumor (MGCT) in the neurohypophysis is very rare, with only a few reported cases1-4 but none with surgical videos. In this report, the endoscopic endonasal transsphenoidal approach for MGCT in the neurohypophysis is presented (Video 1). A 12-year-old girl with ocular pain, fatigue, and nausea presented with gradual onset of quadrant hemianopsia and left oculomotor palsy. Magnetic resonance imaging showed an enhanced mass in the sella turcica with multiple components involving the pituitary gland and stalk. Her endocrinological examination showed decreased levels of pituitary hormones and simultaneously elevated serum levels of alpha-fetoprotein and beta-human chorionic gonadotropin. After pituitary hormone replacement, endoscopic endonasal transsphenoidal surgery was planned. The tumor was strongly adherent to the surrounding structures, and gross total resection was achieved. The histological diagnosis was MGCT with a teratoma component. Postoperatively, her vision and oculomotor palsy improved swiftly, and adjuvant chemotherapy and radiotherapy were administered. In this case, 3-dimensional computer graphics were created from the preoperative computed tomography and magnetic resonance imaging studies. Preoperative simulation with the 3-dimensional computer graphic images and intraoperative verification with indocyanine green images facilitated our understanding of the surrounding anatomy, including the tumor components, pituitary gland, and internal carotid arteries.5 After removal of the tumor, multilayer fascial closure was performed for skull base reconstruction.6 MGCT in the neurohypophysis can be strongly adherent to the surrounding structures, requiring careful dissection and resection under endoscopy. At the last follow-up (8 months after surgery), the tumor was successfully controlled, and the patient had no neurological symptoms with pituitary hormone replacement therapy.

A case of rectal cancer complicated with segmental arterial mediolysis (SAM) safely treated with curative resection - A case report.

INTRODUCTION: Recent advances in diagnostic imaging techniques have led to an increasing number of case reports of segmental arterial mediolysis (SAM). However, reports of abnormalities associated with SAM of abdominal organs, including the bowel, are limited. SAM, a rare vascular disease that causes spontaneous intra-abdominal bleeding, including shock and intestinal ischemia, has been reported to be associated with high mortality, but it has not been reported to coexist with rectal cancer. CASE PRESENTATION: A 74 year-old male was referred to our hospital with a rectal cancer and he was admitted for further examination. Computed tomography angiography (CTA) revealed dissection and aneurysm in the celiac artery, superior mesenteric artery (SMA), and the inferior mesenteric artery were dilated, leading to a diagnosis of SAM. CLINICAL DISCUSSION: Surgery for rectal cancer requires cutting the inferior mesenteric artery. The risk of bleeding during surgery increases when SAM is associated with the inferior mesenteric artery. The radical surgery for rectal cancer was executed without complications, including significant bleeding. This was achieved through careful management of SAM, meticulous control of blood pressure throughout the surgical procedure, and the delicate treatment of the SMA. A pathological diagnosis of the resected inferior mesenteric artery at the time of radical surgery was performed, and a definitive diagnosis of SAM was made. CONCLUSION: We present a first known case in which high anterior resection was successfully performed for rectal cancer complicated by SAM. The relationship between cancer and SAM is unclear and further case accumulation is needed.

Validation of an on-chip p16ink4a/Ki-67 dual immunostaining cervical cytology system using microfluidic device technology.

More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

Solitary Fibrous Tumor in the Retroperitoneal Space Arising from the Diaphragm.

BACKGROUND/AIM: We present a case of solitary fibrous tumor, arising from the diaphragm in the retroperitoneal space, that was resected with robotic assistance. CASE REPORT: An 85-year-old female patient was referred to our hospital for evaluation of a suspected right renal tumor. Abdominal contrast-enhanced computed tomography revealed a tumor (maximum diameter, 36 mm) protruding from the superior pole of the right kidney. The patient was scheduled for robot-assisted, retroperitoneoscopic, partial nephrectomy based on a preoperative diagnosis of renal cell carcinoma. Intraoperative findings revealed that the tumor originated from the diaphragm and had no continuity with the renal parenchyma. Pathological examination revealed a solitary fibrous tumor. CONCLUSION: Solitary fibrous tumors are rare soft-tissue neoplasms with a distinct molecular feature of the fusion of nerve growth factor-inducible A gene-binding protein 2 with signal transducer and activator of transcription 6 gene (NAB2::STAT6). We believe that this is the first reported case of a solitary fibrous tumor arising from the diaphragm in the retroperitoneal space.

High-grade endometrial stromal sarcoma with YWHAE-NUTM2B fusion gene abnormality identified after 10 years of recurrent pulmonary metastases: A case report.

•Endometrial stromal sarcoma is the second most common type of uterine sarcoma.•Endometrial stromal sarcoma has undergone modifications since its proposal.•This case highlights the importance of accurately diagnosing endometrial stromal sarcoma.•Asymptomatic uterine fibroids may not be treated with therapeutic intervention or prompt regular check-ups.

The first case of laparoscopic surgery for cecal cancer occurring in a blind loop.

Cancer occurrence in a blind loop is extremely rare. An 86-year-old Japanese woman underwent colonoscopy for tarry stools and weight loss; it revealed a bypass of the transverse colon and small intestine, cecal cancer, and a polyp. She had suffered from acute appendicitis and had undergone two surgeries at age 25: an appendectomy and then a bypass surgery between the transverse colon and the small intestine. We performed a laparoscopy-assisted ileocecal resection for the cancer and polyp in the blind loop with an end-to-side instrumental anastomosis. The pathological examination demonstrated that the cancer was medullary carcinoma (T2, N0, M0, Stage I) and the polyp was tubular adenoma. Two months have passed since the patient's discharge, and she is free of abdominal complaints. Our literature search identified 10 cases of cancer in a blind loop. Laparoscopy-assisted surgery may be possible in patients who have undergone blind-loop surgery.

Efficacy and safety of dose-dense neoadjuvant chemotherapy with nab-paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer.

OBJECTIVE: Dose-dense chemotherapy has shown a better prognosis than standard interval chemotherapy in adjuvant settings for high-risk breast cancer. This study aimed to evaluate the efficacy and safety of dose-dense nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide as neoadjuvant chemotherapy for human epidermal growth factor 2 (HER2)-negative operable breast cancer. METHODS: Patients with histologically confirmed stage I-III HER2-negative breast cancer were enrolled in this study. Patients received nanoparticle albumin-bound paclitaxel (260 mg/m2) followed by epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks with pegfilgrastim. The primary endpoint was the pathological complete response rate. Patients also underwent prophylactic management for peripheral neuropathy, which involved a combination of cryotherapy, compression therapy using elastic stockings and medications including goshajinkigan. RESULTS: Among the 55 patients enrolled in this study, 13 (23.6%) achieved pathological complete response, of whom 10/26 (38.5%) patients had triple-negative disease and 3/29 (10.3%) had luminal disease. The objective response was observed in 46 (83.6%) patients. Of the 36 patients who were initially planned for mastectomy, 11 (30.6%) underwent breast-conserving surgery after neoadjuvant chemotherapy. The most common grade 3-4 adverse events were myalgia (14.5%), fatigue (12.7%) and elevated transaminase levels (9.1%). No patients experienced febrile neutropenia. Eight (14.5%) patients discontinued treatments due to adverse events. CONCLUSIONS: Neoadjuvant dose-dense biweekly nanoparticle albumin-bound paclitaxel followed by dose-dense epirubicin and cyclophosphamide was effective, especially in patients with triple-negative disease, and feasible with pegfilgrastim support.

Serum vascular endothelial growth factor associated with the progression of granulosa cell tumor: a report of two cases.

BACKGROUND: Granulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5-10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence. CASE PRESENTATION: Case 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin-paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression. CONCLUSIONS: VEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.

Cytological features of stromal spindle cells and their prognostic significance in lung adenocarcinoma.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment play a key role in tumour development, proliferation, invasion, and metastasis. The cytological features of spindle cells including CAFs-defined as stromal spindle cells (SSCs) adjacent to cancer cells-are frequently encountered in pulmonary adenocarcinomas. This study aimed to investigate the association between the presence of SSCs in cytological specimens and the clinicopathological features. METHODS: We evaluated 211 patients with pulmonary adenocarcinoma who underwent surgical resection. All participants had cytological specimens corresponding to the histological specimens available for review. RESULTS: Of the 211 cases examined, 89 were SSC-positive (SSC+ ) and 122 were SSC-negative (SSC- ). SSC+ cases were more frequently associated with higher pathological stage (P < 0.001), lymph node metastasis (P = 0.002), anaplastic lymphoma kinase (ALK) gene rearrangement (P = 0.04), high tumour grade (P < 0.001), solid and micropapillary predominant pattern (P = 0.02), and lymphatic vessel (P = 0.003), blood vessel (P < 0.001), and pleural invasion (P = 0.03) as compared to SSC- cases. Patients with SSC+ adenocarcinoma had a significantly shorter recurrence-free survival than those with SSC- adenocarcinoma (P = 0.009). Cytologically, necrotic background (P = 0.002), mucinous cancer cells (P = 0.02), pleomorphic cells (P < 0.001), and mutual cell inclusions (P = 0.01) were observed more frequently in SSC+ adenocarcinomas. CONCLUSIONS: The presence of SSCs could be an important cytological feature for predicting poor prognosis in lung adenocarcinomas.

Acute arterial occlusive disease due to tumor thrombus from lung metastasis of breast cancer with cartilaginous and osseous metaplasia: a case report.

BACKGROUND: Tumor embolization due to venous infiltration of breast cancer pulmonary metastases is very rare. CASE PRESENTATION: A 72-year-old female was diagnosed with triple-negative breast cancer. Neoadjuvant chemotherapy was discontinued because of progressive disease, and a right mastectomy with sentinel lymph node biopsy was performed. The pathological analysis of surgical specimens revealed carcinoma with cartilaginous and/or osseous metaplasia. At 22 months after surgery, lung metastasis was observed, and 6 months after initiating treatment for lung metastases, she complained of sudden numbness in the left-lower limb with trouble walking. Ultrasonography showed an embolism in the left popliteal artery, and contrast computed tomography showed enlarged lung metastases and infiltration of the left-upper lobe disease into the left superior pulmonary vein and left atrium. Acute arterial occlusive disease in the left-lower limb caused by the tumor embolism was suspected, so an endovascular thrombectomy was performed. Tumor emboli were removed by embolectomy catheter. CONCLUSION: This report of lung metastasis from breast cancer with cartilaginous and/or osseous metaplasia and acute lower-limb artery occlusion due to a tumor thrombus adds useful information to the literature on these extremely rare cases.

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study.

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high-grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR-associated gene mutations in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible according to the criteria. We used frozen tumor tissues to extract DNA and performed next-generation sequencing for 51 targeted genes (including 29 HR-associated genes) in 701 ovarian cancers (298 high-grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low-grade serous cases, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had adjusted hazard ratios of 0.72 (95% CI, 0.55-0.94) and 0.57 (95% CI, 0.38-0.86) for PFS and OS, respectively, compared with those without HRD (p = 0.016 and 0.007). Our study demonstrated that mutations in HR-associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR-associated gene in ovarian cancer.

Improvement of eosinophilic chronic rhinosinusitis after infection with severe acute respiratory syndrome corona virus 2 during dupilumab therapy: A case report.

Eosinophilic chronic rhinosinusitis (ECRS) is an intractable type 2 inflammatory disease of the paranasal sinuses that persists even after endoscopic sinus surgery (ESS) and systemic corticosteroid therapy. Dupilumab, a monoclonal antibody against the shared receptor components of interleukin (IL)-4 and IL-13, is a novel and effective treatment option for ECRS. Herein, an atypical case of ECRS that improved after infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) during dupilumab therapy is reported. A 40-year-old man with a history of ESS for ECRS visited our hospital with complaints of nasal congestion and dysosmia. Nasal endoscopy revealed bilateral nasal polyps occupying the nasal cavity. Computed tomography (CT) revealed a soft tissue density lesion filling all sinuses on both sides. Based on these findings, ECRS recurrence was confirmed; however, 3 years of subsequent corticosteroid therapy did not improve disease activity. Accordingly, dupilumab therapy was initiated, although 6 months of therapy resulted in only slight improvement in ECRS. Eight months after the initiation of dupilumab therapy, the patient was infected with SARS-CoV-2; thereafter, he noticed an improvement in smell. Nasal endoscopy and sinus CT revealed a marked reduction in nasal polyps and soft tissue density lesions of the sinuses, respectively. With continued dupilumab therapy, no re-exacerbation of ECRS was confirmed at the 6-month follow-up from SARS-CoV-2 infection. Currently, there are no reports describing the impact of SARS-CoV-2 infection on ECRS. As such, careful follow-up and accumulation of cases are necessary.

Chlamydia Peritonitis Mimicking Juvenile Carcinomatous Peritonitis Diagnosed by Exploratory Laparoscopy: A Case Report.

Chlamydia trachomatis infections may occur in multiple organs, including the lungs, lymph nodes, peritoneal cavity, and genitourinary systems. This disease results in significant ascites, the swelling of lymph nodes, and elevated tumor markers (CA125), sometimes mimicking an ovarian malignancy. At our hospital, we often perform examination laparoscopic surgery in cases of suspected gynecologic cancers before initial treatment. In this paper, we report the case of a 19-year-old woman who came to our hospital because of an ovarian tumor and ascites. There was no history of sexual intercourse (self-reported). We suspected ovarian cancer from image inspections, so we performed laparoscopic surgery for diagnosis. The final pathological diagnosis was acute-to-chronic inflammation of the bilateral fallopian tubes, and a cytologic examination of the ascites was negative for malignant cells. The C. trachomatis antigen was positive on vaginal examination after the operation. Based on this result, we diagnosed this patient with C. trachomatis infection. Chlamydia peritonitis should be a differential diagnosis for cancer peritonitis in juvenile patients with abnormal ascites. Exploratory laparoscopy should help confirm the pathological diagnosis.

Primary diffuse large B cell lymphoma of the prostate in a patient with HIV infection.

Introduction: Primary prostate lymphomas are very rare; however, the incidence of malignant lymphoma is high among HIV-infected patients. Herein, we report a case of primary diffuse large B-cell lymphoma (DLBCL) of the prostate in an HIV-infected patient. Case presentation: A 47-year-old man presented with miction pain and back pain. Abdominal CT revealed a huge prostate mass extending to the left retroperitoneum. Serum sIL-2R level was abnormally high (2896 U/mL), whereas PSA level was normal. HIV antigen and antibody tests were positive. The patient was diagnosed with DLBCL after a prostate biopsy. Systemic treatments were administered; however, the tumor was refractory, and the patient died 9 months after diagnosis. Conclusion: Prostate malignant lymphomas are rare but should be considered in patients with enlarged prostates and normal PSA levels. It should be noted that HIV patients have a high incidence of malignant lymphomas.

Solitary pulmonary capillary hemangioma mimicking a preinvasive malignant lesion in an asymptomatic middle-aged female patient.

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by a proliferation of capillaries in the alveolar septa, bronchial and venous walls, pleura, and regional lymph nodes. However, the etiology of the disease remains unknown due to its rarity. Therefore, we present a case of a solitary PCH lesion without symptoms in a 38-year-old female patient. According to computed tomography, she was diagnosed with lung carcinoma, indicated by a tiny nodule with ground-glass opacity detected in her right upper lung. However, no other lesions were detected on systemic examination. Consequently, partial lung resection was conducted, since the lesion was suspected of lung adenocarcinoma. Pathologic results showed that the thick alveolar septa were caused by capillary growth without cellular atypia and hardly any infiltration of inflammatory cells. Finally, we diagnosed the pulmonary lesion as PCH, although solitary PCH has previously been reported in a few case reports. Therefore, further case studies are essential to clarify the causes of PCH.

Management of Crohn's disease relapse during neoadjuvant chemotherapy for bilateral breast cancer: a case report.

Diagnosis of breast cancer in a patient with Crohn's disease (CD) is uncommon. However, cytotoxic chemotherapy might help control CD during the treatment period. Here, we report a case of CD relapse during treatment with neoadjuvant chemotherapy (NAC) for bilateral breast cancer. A 39-year-old woman with CD controlled by infliximab and mesalazine was diagnosed with bilateral breast cancer. Infliximab treatment was discontinued temporarily so that the patient could receive NAC. However, her CD symptoms intensified during chemotherapy, and after her symptoms improved after a one-time administration of infliximab, the remainder of NAC was completed with a corticosteroid. Bilateral breast conservation surgery was performed. Histopathological examination revealed partial response of the left breast cancer and no residual cancer in the right breast. Breast irradiation and hormone therapy were added and no signs of recurrence have been observed for 5 years. CD has been well controlled with adalimumab and mesalazine.

Uterine Cervical Adenosarcoma Showing an Endophytic Growth Pattern.

Adenosarcomas are biphasic neoplasms that usually originate in the uterine corpus and comprise a benign epithelial component and a malignant stromal component. Uterine adenosarcomas typically present with abnormal genital bleeding, an enlarged uterus, and a tumor that protrudes into the endometrial cavity. These tumors rarely protrude through the cervical os and are often misdiagnosed as cervical polyps. We present the case of a patient with cervical adenosarcoma with characteristics different from those reported in previous cases. This tumor showed endophytic growth, which is rare in cervical adenosarcomas. No watery discharge or obvious genital bleeding was noted. Although the tumor measured 4 cm, vaginal bleeding was noted only once at 6 months before diagnosis and was in the form of faint brown discharge.