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Atypical lung carcinoid (AC) is widely accepted to recur more often after radical resection than typical lung carcinoid (TC). However, their recurrence rates have never been compared in a multi-state competing risks model. We retrospectively reviewed files from patients with AC and TC who had been radically resected at our European Neuroendocrine Tumor Society Center of Excellence between 2009 and 2020. We estimated the recurrence rates between the AC and TC patients counting unrelated death as a competing event using Aalen-Johansen estimates and compared them using a multi-state Cox model. Finally, we analyzed all AC and TC recurrences as to resection type, pathological stage, resection margin, recurrence site, and time to recurrence. The study included 217 patients, of whom 194 had TC and 23 had AC. The median follow-up was 9.4 years. The AC patients experienced recurrence at a higher rate (hazard ratio [HR] 16.0, 95% confidence interval [CI] 5.3-47.9, p < 0.001). Correspondingly, the 5- and 10-year recurrence rates were 18% and 32% for AC and merely 1.0% and 2.4% for TC. In patients without nodal involvement, AC recurred at a considerably higher rate (HR 41.2, 95% CI 8.7-194.8, p < 0.001) than TC. In both AC and TC, most recurrences were distant and occurred in patients with a resection margin less than 2 cm. We conclude that AC recurs more often than TC, even in patients without nodal involvement at surgery, suggesting that all AC patients regardless of their pathological stage should undergo close follow-up care after surgery.

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Non-Hodgkin's lymphoma are neoplasms derived from T cells and B cells and their precursors in the lymphoid system with higher susceptibility in involvement of extra-nodal sites. Predominant ureteric involvement is an unusual presentation. We present a case of diffuse large B-cell lymphoma with secondary involvement of ureter who had symptoms of urinary tract infection in absence of positive urine culture, non-responsive to broad spectrum antibiotics and masquerading pyogenic infection leading to pyelonephritis with ureteritis. Radiological examination revealed mass like soft tissue thickening of ureter extending from renal pelvis throughout the length of ureter. FNAC as well as biopsy from the periureteric thickening revealed lymphomatous involvement of ureter. The following case report provides insight on differentials and varied symptoms of lymphomatous involvement of ureter.

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Background: In early-stage non-small cell lung cancer (NSCLC), the presence of a ground-glass opacity (GGO) component in the primary lesion on high-resolution computed tomography (CT) is recognized as a favorable prognostic factor. Even in NSCLC with a GGO component, lymph node metastases are occasionally detected during or after surgery. However, the prognostic impact of GGO components in these patients has not been clarified. We aimed to examine the prognostic significance of GGO components as radiological findings of primary lesions of completely resected NSCLC with pathological nodal involvement. Methods: This study included 290 patients (11%) with pathological nodal involvement among 2,546 patients who underwent complete resection of NSCLC at our institution. Patients with an unknown primary lesion (T0) or centrally located lung cancer were excluded. The 290 patients were divided into two groups [i.e., the part-solid ("PS") and "Solid" groups] according to the radiological findings of the primary lesion, and their clinicopathological characteristics and prognoses were compared. Furthermore, a multivariate analysis was performed using the Cox proportional hazards model to examine the factors affecting the overall survival (OS). Results: The OS in the PS group (n=58) was significantly longer than that in the Solid group (n=232; P=0.039). However, multivariate analysis only revealed age [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.15-2.72] and the clinical T factor (HR =1.58; 95% CI: 1.01-2.47), but not the radiological findings of primary lesions, as the independent prognostic factors. Furthermore, the OS did not differ significantly between the PS and Solid groups matched for the clinical T and N factors (n=58 patients each). Conclusions: GGO components in the primary lesion, considered a decisive prognostic factor in early-stage NSCLC, did not affect the prognosis of patients with NSCLC and pathological nodal involvement.

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BACKGROUND: Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. METHODS: Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). RESULTS: Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). CONCLUSIONS: Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

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BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

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PURPOSE: The emergence of chimeric antigen receptor (CAR) T-cell therapy fundamentally changed the management of individuals with relapsed and refractory large B-cell lymphoma (LBCL). However, real-world data have shown divergent outcomes for the approved products. The present study therefore set out to evaluate potential risk factors in a larger cohort. METHODS: Our analysis set included 88 patients, treated in four German university hospitals and one Italian center, who had undergone 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET) before CAR T-cell therapy with tisagenlecleucel or axicabtagene ciloleucel. We first determined the predictive value of conventional risk factors, treatment lines, and response to bridging therapy for progression-free survival (PFS) through forward selection based on Cox regression. In a second step, the additive potential of two common PET parameters was assessed. Their optimal dichotomizing thresholds were calculated individually for each CAR T-cell product. RESULTS: Extra-nodal involvement emerged as the most relevant of the conventional tumor and patient characteristics. Moreover, we found that inclusion of metabolic tumor volume (MTV) further improves outcome prediction. The hazard ratio for a PFS event was 1.68 per unit increase of our proposed risk score (95% confidence interval [1.20, 2.35], P = 0.003), which comprised both extra-nodal disease and lymphoma burden. While the most suitable MTV cut-off among patients receiving tisagenlecleucel was 11 mL, a markedly higher threshold of 259 mL showed optimal predictive performance in those undergoing axicabtagene ciloleucel treatment. CONCLUSION: Our analysis demonstrates that the presence of more than one extra-nodal lesion and higher MTV in LBCL are associated with inferior outcome after CAR T-cell treatment. Based on an assessment tool including these two factors, patients can be assigned to one of three risk groups. Importantly, as shown by our study, metabolic tumor burden might facilitate CAR T-cell product selection and reflect the individual need for bridging therapy.

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Mycosis fungoides is the major form of primary cutaneous T cell lymphoma. Its staging is based on the percentage of body surface involvement and biopsy-proven extra cutaneous nodal or visceral involvement. Literature shows F-18 FDG accumulation in disease-involved nodes and viscera with non-specific uptake due to co-existing inflammation limits its specificity. We report an interesting case of mycosis fungoides with bilateral upper limb edema and share its findings on F-18 FDG PET/CT.

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Subcutaneous scalp manifestations of diffuse large b-cell lymphoma are uncommon and can be an easily overlooked diagnosis. Today we report a rare case of a 60-year-old male with a previous history of treatment and removal of multiple benign cysts who presented to the office for the removal of a subcutaneous mass on the left occipital scalp. Intraoperatively the mass did not resemble a cyst. Pathology results showed diffuse large b-cell lymphoma, highlighting the importance of thorough management of subcutaneous masses.

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BACKGROUND: One of the most prevalent malignancies in India is oral squamous cell carcinoma (OSCC), which is found in more than 90% of cancer cases and has a reduced survival rate of 30%. Matrix metalloproteinases (MMPs) are zinc-containing and calcium-dependent endopeptidases that regulate angiogenesis, migration, and proliferation. MMP-9 in OSCC increases tumor progression through angiogenesis, degrades the basement membrane, and facilitates metastasis by changes in tissue shape. Its overexpression in OSCC has also been shown to have prognostic significance. AIM: This study aims to evaluate the serum levels of MMP-9 in OSCC patients and healthy controls and to correlate with its clinicopathological staging. MATERIALS AND METHODS: This study included 40 individuals; 20 patients with OSCC and 20 healthy controls. MMP-9 was determined in serum samples utilizing enzyme-linked immunosorbent assays. RESULTS:  Descriptive statistics showed that 90% of the patients included in the OSCC groups were above 40 years, and 85% were males. There was a significant increase in the serum level of MMP-9 in OSCC patients compared to healthy controls with a mean difference of +28% (393.21 pg/ml) and a significant p-value of 0.001. (1365.80 ±236.414 pg/ml vs 973.67 ± 83.416 pg/ml). There was a significant increase in the serum levels of MMP-9 among the tumor stages and nodal involvement with a significant p-value of 0.002 and 0.001. No significant association was found between the age and gender groups in OSCC patients and serum levels of MMP-9. CONCLUSION:  MMP-9 was significantly increased in OSCC when compared to healthy controls. Hence, MMP-9 can be used as a prognostic indicator in assessing tumor staging and nodal involvement.

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Introduction: Lip and oral cavity cancer remains the most common cancer among Indian males and third most common cause of cancer-related deaths in India. Cervical lymph node metastasis is one of the most important prognostic factors in oral cavity cancer. The aim of present study was to estimate the prevalence of nodal involvement and analyse patterns of nodal metastasis in oral cavity cancer patients. Methods: This prospective observational study was conducted between January 2019 and June 2020. Patients of oral cavity squamous cell carcinoma undergoing surgery with simultaneous neck dissection were included. Data pertaining to the clinical profile, treatment and histology details were collected and analysed. Results: A total of 63 patients were included in present study. Out of 63 patients, unilateral neck dissection was performed in 47 (75%), while 16 (25%) underwent bilateral neck dissection. Overall clinical and pathological nodal positivity rates were 75% and 52%, respectively. Level I (48%) followed by IIa (20%) were most commonly involved stations. Combined involvement of level IV and V was seen in only 5%, and no skip metastasis was reported in level IV and V. Conclusion: Level I and II are the most commonly involved stations in oral cavity squamous cell carcinoma (SCC). Oral SCC has a predictable nodal spread pattern with no skip metastasis to level IV/V noted in present study. There is a need for good quality randomised control trials to optimise the treatment protocols in clinically node-positive patients with respect to level IIB and V dissection.

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BACKGROUND: Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. PATIENTS AND METHODS: Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. RESULTS: Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P = .009). CONCLUSIONS: Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.

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BACKGROUND: Intravascular large B-cell lymphoma (lVLBCL) is a very rare type of large B-cell lymphoma. METHODS: We conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers. RESULTS: Sixty-five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23-92). Thirty-four patients (64%) had an IPI score >3 and 40 patients (67%) had a performance status ≥2. The most frequent extra-nodal locations were bone marrow (n = 34; 52%), central nervous system (n = 25; 39%), and skin (n = 21; 33%). Nodal involvement and endocrine system were observed in 34% (n = 22) and 18% (n = 12) of all cases, respectively. Twenty-six patients (41%) had macrophage activation syndrome. Tumor cells were frequently CD5 positive (52%) with a non-germinal center origin (86%). BCL2 was expressed in 87% of all samples analyzed (n = 20) and 43% of patients had a MYC/BCL2 double expression. Fifty-six patients were treated with a regimen of chemotherapy containing rituximab, among whom 73% reached complete remission. The median progression-free survival (PFS) and median overall survival (OS) were 29.4 months and 63.8 months, respectively. History of autoimmune disorder (Hazard ratio [HR] 3.3 [1.4-7.8]; p < 0.01), nodal involvement (HR 2.6 [1.4-5.1]; p < 0.01), lack of anthracycline (HR 0.1 [0-0.4] for use; p < 0.001), or no intensification at first-line regimen (p = 0.02) were associated with worse PFS. High-dose methotrexate use was not associated with better PFS or OS. CONCLUSIONS: Our study highlights the aggressive clinical picture of IVLBCL, in particular the frequency of macrophage activation syndrome, and the need for new therapies despite a response to R-CHOP-like regimen similar to non-intravascular diffuse large B-cell lymphomas.

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Purpose: It is not mandatory to report lymphatic vessel invasion in pathology reports of papillary thyroid cancer (PTC) according to the current Union for International Cancer Control (UICC) TNM (tumor, nodes, and metastases) classification. However, there is some evidence for its correlation with lymph node metastasis (LNM) and prognosis. The aim of this study was to explore the clinical implication of lymphatic vessel invasion documentation of PTC because pathology reports play a pivotal role in postsurgical clinical decision-making in endocrine tumor boards. Methods: Patients undergoing postoperative radioiodine treatment for PTC at the University Hospital of Cologne, Germany between December 2015 and March 2020 were identified. Pathology reports were screened for documentation of lymphatic vessel invasion. Demographics and clinicopathologic data of patients documented, including lymphatic vessel invasion and lymph nodal involvement were analyzed. Results: A total of 578 patients were identified and included. Lymphatic vessel invasion was reported in pathology reports of 366 (63.3%) and omitted in 112 (36.7%) patients. Positive lymphatic vessel invasion (L1) was diagnosed in 67 (18.3%) of 366 patients and was documented as absent (L0) in 299 (81.7%) patients. Lymph nodal (N) status was positive (N+) in 126 (45.6%) and negative (N0) in 150 (54.3%) of these patients. In 54 (80.6%) L1 cases N+ status and in 137 (65.6%) L0 cases N0 status was diagnosed. In 13 (19.4%) cases with L1 status, there were no LNMs (L1 N0). In total, 72 (34.4%) patients had LNM despite L0 status (L0 N+). The sensitivity and specificity of LVI reporting for LNM were 0.42 and 0.91, respectively. Conclusion: In routine pathology reports of PTC used for indication to postoperative radioiodine treatment by a German endocrine tumor board, lymphatic vessel invasion was found to be reported inconsistently and mostly as L0. L1 diagnoses, however, reliably correlated with reported LNM and might, thus, be relevant for clinical decision-making. For this reason, we advocate for standardized pathologic reassessment of lymphatic vessel invasion, in particular for cases where lymph nodes are not included in the pathologic specimen and if L0 is documented.

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B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a malignancy of dysregulated lymphocytes in bone marrow and lymphatics. Extra-nodal involvement has been previously cited to affect areas like the lungs, skin, central nervous system, and kidney. Gastrointestinal (GI) involvement in patients with chronic CLL/SLL is rare. We report a unique case of CLL/SLL found incidentally in a 71-year-old asymptomatic female undergoing a screening colonoscopy. Patients with GI infiltration of CLL/SLL may be asymptomatic like the patient described in this report, or present with symptoms that may resemble inflammatory bowel disease, microscopic colitis, or colon cancer. Therefore, it is important to remain vigilant for the occurrence of other malignancies during the follow-up of CLL/SLL patients.

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BACKGROUND: The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. PATIENTS AND METHODS: N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. RESULTS: The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11-110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1-8)). These 6 patients were highly node positive with median 4.5 (2-9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. CONCLUSION: A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.

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In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.

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BACKGROUND: The advantage of up-front neck dissection (UFND) followed by chemoradiotherapy (CRT) for hypopharyngeal cancer (HPC) with advanced neck involvement remains controversial. We aimed to determine the indications. METHODS: The data of 41 and 14 patients with stage IVA/B (T1-T3 and ≥N2a) HPC who underwent UFND followed by CRT and received CRT, respectively, were retrospectively analyzed and compared. RESULTS: The 5-year overall survival (OS) and disease-specific survival rates for the UFND and CRT groups were 61% and 52% (p = 0.1019), and 89% and 74% (p = 0.2333), respectively. Moreover, patients aged ≥70 years or those with a pulmonary disease history had a significantly poorer prognosis due to aspiration pneumonia in the UFND group. The 5-year regional control (RC) for the UFND and CRT groups were 92% and 57%, respectively (p = 0.0001). CONCLUSIONS: UFND followed by CRT was feasible with satisfactory RC. To further improve OS, aspiration pneumonia prevention is essential.

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BACKGROUND AND PURPOSE: Although tumor size and nodal status are the most important prognostic factors, it is believed that nodal status outperforms tumor size as a prognostic factor. In particular, when patients have a nodal stage greater than N2 (more than nine positive lymph nodes), it is well accepted that tumor size does not retain its prognostic value. Even in the newest American Joint Committee on Cancer (AJCC) prognostic staging system, which includes molecular subtype as an important prognostic factor, T1-3N2 patients are categorized as the same population. The same is true for T1-4N3 patients. Moreover, some physicians have speculated that for tumors staged N2 or greater, the smaller the tumor is, the more aggressive the tumor. Thus, this study aims to investigate the prognostic value of tumor stage (T stage) in patients with extensive nodal involvement and to compare the survival of T4N × M0 and T × N3M0. PATIENTS AND METHODS: Female breast cancer patients with nine or more positive lymph nodes or with T4 tumors were identified in the SEER registry between 2010 and 2015. The effect of T stage on breast cancer-specific survival (BCSS) was assessed using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression modeling. Survival comparison of T4NxM0 and TxN3M0 patients was also achieved using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression model. RESULTS: Overall, 21,696 women with N2-3 tumors were included from 284,073 patients.T stage, nodal stage (N stage), ER, PR, HER2 and grade were all independent prognostic factors (p <0.001). HRs for ER, PR, HER2, grade, and N stage were 0.662 (0.595-0.738), 0.488 (0.438-0.543), 0.541 (0.489-0.598), 1.534 (1.293-1.418) and 1.551 (1.435-1.676), respectively. Notably, HER2 positivity was correlated with better BCSS possibly due to the wide adoption of anti-HER2 therapy. Using T1 as a reference, HRs of T2, T3, and T4 were 1.363 (1.200-1.548), 2.092 (1.824-2.399) and 3.497 (3.045-4.017), respectively. The same results held true when subgroup analysis based on N stage were conducted. In the two subgroups, namely, women staged as T1-3N2 and women staged as T1-4N3, T stage was also a significant negative prognostic factor independent of ER, PR, HER2 and grade. Moreover, 8,328 women staged as T4 with different nodal statuses were also identified from the whole database. When we compared T4Nx with TxN3, it was found that T4 tumors exhibited worse outcomes than N3 tumors independent of other prognostic factors. When molecular subtype was included in the subgroup analysis, survival could not be distinguished between T4 and N3 only in TNBC. CONCLUSIONS: In patients with extensive nodal status, tumor stage remains a prognostic factor independent of other factors, such as ER, PR, HER2, and grade. In patients with T4Nx or TxN3 tumors, T4 tumors exhibit worse outcomes than N3 tumors independent of other prognostic factors. The AJCC staging system should be modified based on these findings.