Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

Virulent Pseudomonas aeruginosa pneumonia in an immunocompetent adult associated with a home whirlpool bath: A case report.

We present a case of life-threatening pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) in a healthy 67-year-old man. Rapid disseminated infection resulted in the right hemorrhagic pneumonia and bacteremia. Antimicrobial therapy had limited effects, radical pneumonectomy eventually resolved the prolonged infection. Concurrently, we explored the environmental factors responsible for fulminant P. aeruginosa infection. Multi-locus sequence typing demonstrated that P. aeruginosa isolated from the patient was identical to that collected from home whirlpool bath by the common virulent factor gene. Massive inhalation of contaminated aerosol and pathogen virulence may have synergistically contributed to the severity in this case.

[The Outcome of Second Anatomical Pulmonary Resection for Ipsilateral Metachronous Lung Cancer].

INTRODUCTIONS: When the first intervention for lung cancer is anatomical resection, the ipsilateral repeat anatomical resection for metachronous second lung cancer becomes technically challenging. Herein, we report the outcomes of second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution. SUBJECTS: Sixteen consecutive patients[ 10 men and 6 women, average age 70( range 59~81) years] were reviewed in this retrospective study. These patients underwent ipsilateral repeat anatomical resection for metachronous second lung cancer between 2009 and 2020. RESULTS: All case required right-sided lung resections. The previous interventions of patients included upper lobectomy, lower lobectomy, middle lobectomy, S2 segmentectomy, and S6 and S10a segmentectomy in 9, 4, 1, 1, and 1 case, respectively. The second surgical interventions were middle lobectomy, S6 segmentectomy, upper lobectomy, lower lobectomy, S1 segmentectomy, and S2 segmentectomy, in 6, 4, 2, 2, 1, and 1 case, respectively. Postoperative complications occurred in three patients. The median follow-up period was 53.5 months. Three patients died during the follow-up period. Of the 13 patients still alive, 6 had recurrence. The five-year overall survival rate was 80%. CONCLUSIONS: Although only a few cases were assessed, the prognosis after second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution was satisfactory.

[Completion Pneumonectomy for the Recurrence of Lung Cancer].

INTRODUCTIONS: The morbidity and mortality after completion pneumonectomy (CP) are reportedly high. We, herein, report the outcomes of CP at our institution. SUBJECTS: Nine consecutive patients [7 men and 2 women, average age of 72 years(range 44~84 years)] who underwent CP for recurrence of lung cancer during 2012~2018 were retrospectively reviewed. RESULTS: Right-sided sleeve CP was performed in two cases and left-sided CP in seven cases. The indications for surgery were lymph node metastasis of the cancer, pulmonary metastasis, and bronchial stump recurrence in 4, 3, and 2 cases, respectively. Postoperative complications occurred in six patients. One of the patients who underwent right sleeve pneumonectomy developed bronchopleural fistula and died 68 days after the surgery. The mean follow-up period was 33 months, and four patients died during follow-up. Of the 5 patients still alive, 4 had no recurrence and 1 had recurrence in the stump of the main bronchus. The five-year overall survival rate was 78%. CONCLUSIONS: Although only few cases were assessed, the prognosis after CP at our institution was relatively good.

Intrapulmonary solitary fibrous tumour: a case report.

Solitary fibrous tumours (SFTs) mainly originate from the visceral pleura and may protrude to the thoracic cavity, but intrapulmonary SFTs are extremely rare. We describe a rare case of SFT arising in the right lung of an 83-year-old man who underwent surgical excision. Chest computed tomography (CT) revealed a 10-mm tumour in the lower lobe of the right lung. The size of tumour gradually increased and reached 17 mm 2 years after the first radiologic examination. Considering the possibility of malignancy, wedge resection of the right lower lobe was performed via video-assisted thoracic surgery. Microscopically, the tumour consisted mainly of spindle-shaped cells. Immunohistochemical staining indicated the tumour was positive for CD34, STAT6, vimentin and bcl-2, but negative for cytokeratins, D2-40 and S-100. Based on the histological findings, the tumour was diagnosed as SFT. The patient has been in good health for 6 months since the surgery.

Can the Japanese National Clinical Database risk calculator predict long-term survival of patients who undergo palliative segmentectomy for primary lung cancer?

OBJECTIVES: Selection criteria for palliative limited surgery in patients with non-small cell lung cancer (NSCLC) can vary by institution or surgeon. We retrospectively reviewed outcomes of poor-risk patients who underwent palliative segmentectomy (PS), using the National Clinical Database Risk Calculator (RC). METHODS: We retrospectively analyzed medical records of patients with NSCLC tumors ≥ 20 mm and consolidation/tumor ratios ≥ 0.5 on computed tomography, who underwent PS from January 2009 to March 2016. Median follow-up time was 47 months (range 2-102 months). RESULTS: We enrolled 67 patients (median age: 73.0 years), of whom 54 received thoracoscopic surgery and 28 received medial lymph-node dissection. The RC's mean predictive probability rate for perioperative mortality or severe complications was 7.1%. Of the 67 patients, 24 patients (43.0%) suffered post-surgical complications, including 2 (3%) who died in hospital; 17 eventually suffered NSCLC recurrences and/or metastases, 11 eventually died from NSCLC, and 17 died from other diseases. Five-year overall survival (OS) was 59.4%. When the patients were divided into high-risk (HR) and low-risk (LR) groups based on the RC, 5-year OS was significantly less in the HR group (43.9%) than in the LR group (82.2%; P < 0.05). CONCLUSION: The RC, which was developed primarily to determine perioperative risk, can predict long-term prognosis for compromised patients who undergo PS.

Reciprocal expression of trefoil factor-1 and thyroid transcription factor-1 in lung adenocarcinomas.

Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in thyroid transcription factor-1 (TTF-1)/NK2 homeobox 1 (NKX2-1)-positive terminal respiratory unit (TRU) types and rarely in non-TRU types. To elucidate the molecular characteristics of the major subtypes of non-TRU-type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non-TRU types). A characteristic of non-TRU-type cell lines was the strong expression of TFF-1 (trefoil factor-1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF-1 was positive in 31 cases (13%). Expression of TFF-1 was frequently detected in invasive mucinous (14/15, 93%), enteric (2/2, 100%), and colloid (1/1, 100%) adenocarcinomas, less frequent in acinar (5/24, 21%), papillary (7/120, 6%), and solid (2/43, 5%) adenocarcinomas, and negative in micropapillary (0/1, 0%), lepidic (0/23, 0%), and microinvasive adenocarcinomas or adenocarcinoma in situ (0/9, 0%). Expression of TFF-1 correlated with the expression of HNF4-α and MUC5AC (P < .0001, P < .0001, respectively) and inversely correlated with that of TTF-1/NKX2-1 (P < .0001). These results indicate that TFF-1 is characteristically expressed in non-TRU-type adenocarcinomas with gastrointestinal features. The TFF-1-positive cases harbored KRAS mutations at a high frequency, but no EGFR or ALK mutations. Expression of TFF-1 correlated with tumor spread through air spaces, and a poor prognosis in advanced stages. Moreover, the knockdown of TFF-1 inhibited cell proliferation and soft-agar colony formation and induced apoptosis in a TFF-1-high and KRAS-mutated lung adenocarcinoma cell line. These results indicate that TFF-1 is not only a biomarker, but also a potential molecular target for non-TRU-type lung adenocarcinomas.

Successful treatment of post-operative peripheral bronchopleural fistulas using endobronchial Watanabe spigots.

Post-operative peripheral bronchopleural fistulas (BPF) are sometimes caused by post-operative pneumonia and empyema. Conservative treatment options such as administration of antibiotics and chest tube drainage can have limited outcomes in certain cases. Bronchial occlusion is an effective treatment option if the target bronchi for BPF are identified. This case study describes a successful bronchial occlusion for peripheral BPF with endobronchial Watanabe spigots (EWSs) and a digital drainage system. This case involved a 70-year-old man who developed a post-operative peripheral BPF after a left upper lobectomy. Bronchial occlusion with EWS was performed because the target bronchi responsible for BPF were clearly detected by a chest computerized tomography scan. The effectiveness of the occlusion was confirmed with the use of a digital drainage system immediately after the procedure was completed. The chest tube was removed one week following the bronchial occlusion procedure.

Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma.

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell-cell and cell-matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O-glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.

Bronchoscopic observation with linked colour imaging.

We report two cases of the comparison of diagnosis made with linked color imaging (LCI) and conventional white-light imaging (WLI) on the same patients. In case 1, a 75-year-old man in whom right upper lobectomy with mediastinal lymph node dissection was performed due to lung cancer had signs of bronchitis on postoperative day 8. The LCI demonstrated slight inflammatory changes that were not detectable with the conventional WLI on the tracheal wall. In case 2, in a 61-year-old woman who was diagnosed with adenoid cystic carcinoma, the bronchial wall was checked to confirm the extent of the tumour. The submucosal vascularity and tumour margin on the bronchial mucosa were better visible on LCI than on WLI. We could easily detect the mucosal inflammatory lesion and the malignant lesion with LCI in comparison with conventional WLI. Both mucosal inflammatory and malignant lesions were better visible with LCI in comparison to WLI.

Left mediastinal node dissection after arterial ligament transection via video-assisted thoracoscopic surgery for potentially advanced stage I non-small cell lung cancer.

BACKGROUND: Left mediastinal node dissection during lung cancer surgery can be difficult because paratracheal and subcarinal lymph nodes are concealed by mediastinal structures. Arterial ligament transection (ALT) offers a wide surgical view of concealed mediastinal spaces, thus enabling extended en bloc lymph node dissection (LND). We analyzed surgical outcomes of patients who underwent extended LND after ALT via video-assisted thoracoscopic surgery (VATS) for potentially node-positive clinical stage I non-small cell lung cancer (NSCLC). METHODS: We retrospectively investigated the medical records of 75 patients who had undergone extended mediastinal node dissection after ALT via VATS for potentially node-positive NSCLC at our centers during the period from September 2008 through November 2015. Operative data and rates of overall survival (OS), in addition to mortality and morbidity, were analyzed in relation pathological stage and nodal stage. RESULTS: Operative time was 238±58 minutes, and an average of 32.7±12.9 hilar and mediastinal lymph nodes were dissected. Lymph node metastases were detected in 34 patients (6 pN1 patients, 27 pN2 patients, and 1 pN3 patient). Mediastinal lymph node metastases were detected around the carina (stations 2L, 4L, and 7) in 19 of 27 patients with pN2 cancer. Nineteen patients had a total of 24 postoperative complications. Recurrent nerve paralysis was the most frequent complication (n=11) but resolved in eight patients during follow-up. Survival rates at 3 and 5 years were 92.2%/88.4%, 100.0%/60.0%, and 87.7%/81.0% for p-stage I, II, and III, respectively, and 92.2%/88.4%, 100.0%/60.0%, and 87.4%/80.7% for pN0, pN1, and pN2, respectively. CONCLUSIONS: Extended mediastinal node dissection after ALT allowed detection of lymph node micrometastases in selected patients with potentially node-positive left NSCLC and may improve outcomes.

Recommendations for perioperative management of lung cancer patients with comorbidities.

OBJECTIVES: To improve surgical outcomes, clinicians must provide optimal perioperative care for comorbidities identified as significant factors in risk models for patients undergoing lung cancer surgery. METHODS: We reviewed trends in perioperative care for idiopathic pulmonary fibrosis, cardiovascular diseases, and end-stage renal diseases in patients undergoing lung cancer surgery, as large clinical databases indicate that these comorbidities are significant risk factors for lung cancer surgery. Articles identified by keyword searches were included in the analysis. RESULTS: Significant predictive factors for acute exacerbation of idiopathic pulmonary fibrosis were identified. However, no effective perioperative care was identified for prevention of acute exacerbation of interstitial pneumonia. The timing of coronary revascularization and antithrombotic management for cardiovascular diseases are subjects of ongoing research, and acid-base balance is essential in the management of hemodialysis patients with end-stage renal diseases. CONCLUSIONS: To improve surgical outcomes for lung cancer patients, future studies should continue to study optimal perioperative management of comorbidities.

Establishment of highly metastatic KRAS mutant lung cancer cell sublines in long-term three-dimensional low attachment cultures.

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3-4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.

Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas.

The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we carried out whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2-1/TTF-1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2-1/TTF-1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1/TTF-1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2-1)/thyroid transcription factor 1 (TTF-1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1/TTF-1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF-1-postive/hepatocyte nuclear factor 4-α (HNF4-α)-negative and TTF-1-negative/HNF4-α-positive groups. NKX2-1/TTF-1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2-1/TTF-1 gene body was highly methylated in NKX2-1/TTF-1-negative cases, including those without the NKX2-1/TTF-1 mutations. The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas.

Revival of impaired lung perfusion after sleeve lobectomy.

Sleeve resection, a mainstay for centrally-located lung cancer, is a challenging procedure when the preserved lung is impaired. We herein reported a 61-year-old male who underwent right upper sleeve lobectomy for squamous cell carcinoma located at the orifice of the upper bronchus. The tumor invaded the main bronchus. A lung perfusion scan showed severe impairment, while the right middle and lower lobes were well expanded. Not only the spirogram, but also the lung perfusion in the residual lung, had markedly recovered at 2 months after the right upper extended sleeve lobectomy. The patient is currently living his normal daily life. Residual lung perfusion can be revived, even if it is impaired preoperatively.

Incidental bronchial injury by soft coagulation.

Soft coagulation is a hemostat system of electrosurgical units, which automatically regulates its output voltage below 200 V, to avoid excessive output that causes carbonization of the target tissue. However, this new minimally invasive technology still has the potential risk of tissue damage during surgery. We encountered three patients with bronchial injury caused by the above system; one of whom had bronchopleural fistula. This is believed to be the first report emphasizing the adverse effects of the soft coagulation system in thoracic surgery, giving a warning to the application of this convenient device.

Polyglycolic acid mesh occlusion for postoperative bronchopleural fistula.

BACKGROUND: Postoperative bronchopleural fistula is one of the most life-threatening complications after anatomical pulmonary resection. Bronchopleural fistula may cause empyema and aspiration pneumonia with subsequent acute respiratory distress syndrome. Surgical interventions for bronchopleural fistula can prolong hospitalization and impair postoperative quality of life. Postoperative care requires minimally invasive endoscopic occlusion. METHODS: We retrospectively reviewed the records of 7 patients who developed bronchopleural fistula among 689 patients who underwent segmentectomy or lobectomy without sleeve resection for lung cancer in Jichi Medical University from 2009 to 2013. Bronchopleural fistula occurred in the right lower bronchial stump in 3 patients, in the superior segmental bronchus of the right lower lobe in 2, in the superior segmental bronchus of the left lower lobe in one, and in the right intermediate bronchus in one. Flexible bronchoscopy was used to occlude 3-mm fistulas with polyglycolic acid mesh in 2 patients. Larger fistulas in 5 patients were occluded with polyglycolic acid mesh plus fibrin glue to secure the mesh. The median procedure was 37 min. Procedures were considered complete upon resolution of air leakage from the chest drainage system. RESULTS: Bronchoscopic interventions for bronchopleural fistula were repeated an average of 2 times. No procedure-related complications or death occurred. Bronchoscopic interventions were successful in all patients. CONCLUSIONS: Bronchoscopic occlusion with polyglycolic acid mesh with or without fibrin glue is easy and feasible as the first step in postoperative management of bronchopleural fistula.

Aberrant aneurysm of adult-type pulmonary sequestration: report of a case.

Aberrant pulmonary artery exposed by high-blood pressure over a long period in adult-type pulmonary sequestration can be susceptible to arteriosclerotic change and aneurysmal formation. Dividing this aneurysmal artery has a risk of stump leakage and aneurysm. We herein report a 64-year-old man with an aberrant aneurysm of intralobar pulmonary sequestration. Thoracoscopic resection of the sequestrated lung was performed uneventfully by prior endovascular occlusion of the aberrant aneurysm.

[Diaphragmatic hernia complicated with diaphragmatic resection by automatic stapling device].

Nowadays, a diaphragmatic lesion is sometimes resected with use of an automatic stapling device, especially through video-assisted thoracoscopic procedure. We herein report 2 patients with a diaphragmatic hernia after diaphragmatic resection by automatic stapling devices. Etiology and cause of postoperative diaphragmatic hernia are discussed. Diaphragmatic resection by mechanical stapler was performed for thymic epithelial tumor recurring at the diaphragmatic pleura in both patients: 48-year-old man and 72-year-old woman. The former patient underwent a right diaphragmatic resection (3×4 cm in size) with a cartridge of mechanical stapler. Computed tomography (CT) and magnetic resonance imaging showed asymptomatic right diaphragmatic hernia 2 months after surgery. No symptom and progression occurred 8 years later. The latter patient underwent a right diaphragmatic resection (6×7 cm in size) with 2 cartridges of mechanical stapler. Diaphragmatic hernia advanced 7 months after surgery and required surgical intervention. Diaphragmatic repair was successful with the use of 8×6 cm expanded polytetrafluoroethylene patch. Surgical stump after diaphragmatic resection with automatic stapling device is easy to rupture during diaphragmatic movement synchronized with respiratory movement. Diaphragmatic resection with use of stapling device, which is a simple procedure, should be contraindicated.

[The case of a giant malignant phyllodes tumor of the breast].

A 75-year-old female patient complained of a mass in her left breast 2 years ago. The patient experienced a rapid enlargement of the mass 2 months later and visited our hospital. A computed tomography (CT) scan indicated a 25-cm tumor with infiltration of the left breast skin. Pectoral muscle invasion was considered. Swelling of the axillary lymph node and remote metastases were not found. A needle biopsy indicated a phyllodes tumor. A pectoral muscle-preserving mastectomy was undertaken. The tumor weighed 7.1 kg. Pathological examination indicated hyperplasia of the stroma and part of the epithelium, which had invaded the skin layer and fatty tissue. The pathological diagnosis was a malignant phyllodes tumor. This paper reports the case of a giant malignant phyllodes tumor.