Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is widely used in patients who receive neoadjuvant chemotherapy (NAC). Still, axillary lymph node dissection (ALND) is recommended for patients with any axillary residual disease after NAC. The necessity of ALND in patients with minimal axillary disease is unclear. We aim to investigate regional recurrence rates in patients with limited axillary residual disease after NAC underwent SLNB + image-tailored axillary surgery and adjuvant radiotherapy (RT). METHODS: Patients with clinical stages were T1-3 and N1 at the time of diagnosis, clinically good or complete axillary response after NAC, and limited axillary residue (≤ 3 pathological lymph nodes) with favorable response to NAC in the final pathological examination were included in the study. All patients underwent SLNB + image-tailored axillary surgery. Peripheral lymphatic radiotherapy was applied, and no further surgery was performed in patients with compatible radiology and pathology results. RESULTS: Our study, which evaluated 139 patients with a median age of 47 years, found that the median number of excised lymph nodes was 4. Notably, 46% of patients had between 1 and 3 lymph nodes excised, while 45% had between 4 and 6. Only 9% of patients had ≥ 7 lymph nodes. 83(60%) of the patients underwent breast-conserving surgery (BCS), and 56(40%) underwent mastectomy. The study's median follow-up period was 44 months. During this duration, one breast recurrence (0.7%), one supraclavicular recurrence (0.7%), and six systemic recurrences (4.3%) were observed. No axillary recurrence occurred within the follow-up period. CONCLUSIONS: Patients presenting with pathological-suspicious ≤ 3 lymph nodes on imaging and showing a good response to NAC can be considered suitable candidates for SLNB + image-tailored axillary surgery, followed by adjuvant RT instead of ALND.

Multiple combinations of melanocytic and vascular endothelial markers enhance the detection rate of lymphovascular invasion in cutaneous melanoma.

BACKGROUND: Lymphovascular invasion (LVI) is believed to be the mechanism by which melanoma cells can disseminate to regional lymph nodes and distant sites and may be predictive of adverse outcome. Lymphovascular invasion often difficult to detect on hematoxylin-eosin (HE) stained sections, are readily identified with dual immunohistochemistry (IHC) for melanocytic and vascular markers. METHODS: A total of 100 primary cutaneous malignant melanoma cases that had a Breslow thickness of 1-4 mm and lacked LVI by conventional HE assessment were included. We compared the LVI detection rates of double staining for CD31/S100 and CD34/S100, and D2-40/S100, and examined the association of LVI with clinical outcomes. RESULTS: The dual immunohistochemical positivity for CD31/S100, CD34/S100, and D2-40/S100 were 40(40%), 17(17%) and 35(35%), respectively. On multivariate analysis, LVI was an independent predictor of SLN status. Multivariate analysis revealed that LVI and male gender were independent risk factors for overall survival. CONCLUSIONS: The recognition of LVI is improved by dual IHC and predicts SLN metastasis. The detection of LVI using dual IHC, especially by a combination of CD31/S100 and D2-40/S100 is a useful step that inclusion should be recommended in basic evaluation parameters for cutaneous melanoma.

Loss of stromal CD73 expression plays a role in pathogenesis of polypoid endometriosis.

PURPOSE: To investigate whether CD73 had a role in the pathogenesis of polypoid endometriosis. METHODS: Our study included 15 cases of polypoid endometriosis, which were diagnosed between 2005 and 2019. Clinical findings were gathered from archive files of relevant clinics and pathology reports. All glass slides were re-examined for confirmation of the diagnosis and the detection of additional microscopic findings. An immunohistochemical examination was performed using anti CD73 antibodies in 15 cases of polypoid endometriosis, and also in a control group that contained 9 cases of endometrial polyps and 9 cases of ovarian conventional endometriosis. RESULTS: In addition to standard gynecologic operations, major non-gynecologic procedures had to be performed in 7 cases. In two cases, the surgical team comprised only general surgeons, and a misdiagnosis of carcinoma was made during the frozen section in one case. The majority of the cases displayed gross polypoid lesions that measured 0.7-13 cm. The most common sites were the ovary and rectosigmoid colon. Microscopically, all lesions exhibited a fibrovascular stroma reminiscent of endometrial stroma, whereas glandular features varied. Immunohistochemical examinations revealed a significant loss of CD73 expression in the stroma of polypoid endometriosis in contrast to the control cases, which retained stromal CD73 expression (p < 0.0001). CONCLUSION: Both pathologists and surgeons performing abdominal surgeries should be aware of polypoid endometriosis because it mimics malignancy with its clinical, gross, and microscopic features. We also conclude that loss of stromal CD73 expression, due to its effect on the extracellular ATP/adenosine balance, may contribute to the pathogenesis of this rare form of endometriosis.

Re-evaluation of glomerulitis using occlusion criteria based on the Banff 2013 revision: a retrospective study.

The presence of occlusion/near-occlusion of glomerular capillaries was recently added to the existing definition of glomerulitis (g). We retrospectively re-evaluated 135 renal allograft biopsies regarding g to ensure no antibody-damaged grafts were missed. Previous and revised g scores (pg and rg, respectively) were compared for clinicopathologic correlations. The g score did not change in 100 (74.1%) biopsies. Thirty-five (25.9%) biopsies were changed to a lower score. Sensitivity and specificity of pg and rg for the presence of donor-specific antibodies (DSA) were 76% vs. 58% and 70% vs. 79%, respectively. Pg score indicated graft loss with 65% sensitivity and 63% specificity, whereas rg showed 46% sensitivity and 71% specificity. Area under the curve (AUC) values in ROC analysis for DSA and graft loss were as follows: pg, 0.773; rg, 0.693; and pg, 0.635; rg, 0.577, respectively. A comparison of the two AUC values revealed a significant difference between pg and rg only for DSA (P = 0.0076). Pg and post-transplant time of biopsy independently predicted graft loss, whereas rg did not. In conclusion, revised g scores showed lesser sensitivity but higher specificity for DSA and graft loss. Recent definition of g missed antibody-mediated rejection in few cases, and it was not an independent predictor for graft loss.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year-OS (P=.001) and 10 year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

Lipoadenoma of the Submandibular Gland.

We report a case of an oncocytic lipoadenoma of the submandibular gland, which is a very rare benign tumor of the salivary gland. The patient was a 36-year-old man with a right submandibular mass measuring 29 × 1.3 × 1.2 cm. When the preoperative diagnostic tools were insufficient to rule out malignancy and for definite diagnosis, total removal of the gland was performed. Histopathologically, microscopic examination revealed a well-circumscribed tumor that is surrounded by a thin, fibrous capsule. The majority of the tumor consisted of adipocytes and normal components of salivary gland tissue. Oncocytic cells were observed only focally. Physicians should keep in mind that salivary glands may rarely exhibit this special tumor growth pattern.

New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer.

BACKGROUND: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. METHOD: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]). CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.

Gonadoblastoma with Dysgerminoma in a Virilized Adolescent with Karyotype 46,XX: A Case Report and Review of the Literature.

Gonadoblastoma is a rare ovarian tumor composed of sex cord cells and primitive germ cells. While the majority of gonadoblastomas are found in individuals with 46,XY gonadal dysgenesis, they are also rarely seen in patients with a 46,XX karyotype. We report a case of a fourteen-year-and-six-month-old girl presenting with an uncommon cause of virilization due to a virilizing ovarian tumor. The patient underwent bilateral salpingo-oophorectomy. Upon histopathological examination, the excised tumor was confirmed to be bilateral gonadoblastoma, with dysgerminoma on the left side. Malignant gonadal tumors should be considered in cases of primary gonadal insufficiency with a 46,XX karyotype and progressive virilization. Even when laboratory and imaging tests show no abnormalities, a gonadal biopsy should be considered.

The Role of Morphology in Predicting Fumarate Hydratase-deficient Uterine Leiomyomas in Young Women.

Hereditary leiomyomatosis and renal cell carcinoma is caused by germline mutations in the fumarate hydratase (FH) gene and is associated with an increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma. Pathologic evaluation of uterine leiomyoma can provide an opportunity for early recognition of the syndrome. We reviewed all archived slides of the cases to identify the characteristic morphologic features described for FH-deficient leiomyomas. We performed immunohistochemistry on whole sections of patients with uterine leiomyoma to evaluate for both FH and 2-succinocysteine (2SC) expression. Of the 106 cases, 19 showed the characteristic eosinophilic nucleoli with perinuclear halos, and 24 revealed a characteristic eosinophilic cytoplasmic inclusion consisting of pink globules present within the cytoplasm. Both of these morphologic findings were present together in 15 cases, and hemangiopericytomatous vessels were detected in 23 cases. The loss of FH protein expression was detected in 14 out of 106 cases (13%), and 13 out of 106 cases (12%) were positive for 2SC. We detected 10 cases with both 2SC-positive and FH expression loss. The presence of eosinophilic nucleoli with perinuclear halos and eosinophilic cytoplasmic inclusion was associated with both loss of FH protein expression and 2SC positivity ( P < 0.001). These findings underscore the importance of hematoxylin and eosin-based predictive morphology in FH-deficient uterine leiomyomas. Therefore, morphologic assessment of uterine leiomyomas for features of FH deficiency can serve as a screening tool for hereditary leiomyomatosis and renal cell carcinoma syndrome, allowing patients to be divided according to their hereditary risk assessment.

Ductal Carcinoma In Situ Arising in Sentinel Axillary Lymph Nodes Excised From Patients With Breast Carcinoma - A Potential Diagnostic Pitfall. Report of Two Cases.

We present two cases of ductal carcinoma in situ (DCIS) that arose in axillary lymph nodes excised as the sentinel lymph node from two patients with breast carcinoma. The patient ages were 72 and 36 years and both patients underwent mastectomy and axillary lymph node dissection. In addition to DCIS in the sentinel lymph node, the first patient had a wide DCIS and microinvasion in the ipsilateral breast and a micrometastasis in another sentinel lymph node. The second patient was operated on after neoadjuvant chemotherapy and had DCIS and a small focus of invasion, in addition to invasive and in situ ductal carcinoma in the lymph node having signs of chemotherapy-induced regression. The presence of DCIS was confirmed by use of the immunohistochemical method with antibodies against myoepithelial cells. As a potential source of cellular origin, DCIS was accompanied by benign epithelial cell clusters in the lymph node in both cases. Morphologic and immunohistochemical features were similar in breast and lymph node neoplasms. We conclude that DCIS may rarely develop from benign epithelial inclusions in the axillary lymph node and is a potential diagnostic pitfall in cases having ipsilateral breast carcinoma.

Pure Tubular Breast Carcinoma: Clinicopathological Characteristics and Clinical Outcomes.

Objective: Tubular breast carcinoma (TBC) is a rare subtype of breast carcinoma (BC) with a good prognosis. In this study, we aimed to assess the clinicopathological characteristics of pure TBC (PTBC), analyze factors that may influence long-term prognosis, examine the frequency of axillary lymph node metastasis (ALNM), and discuss the need for axillary surgery in PTBC. Materials and Methods: Fifty-four Patients diagnosed with PTBC between January 2003 and December 2020 at Istanbul Faculty of Medicine were included. Clinicopathological, surgical, treatment, and overall survival (OS) data were analyzed. Results: A total of 54 patients with a mean age of 52.2 years were assessed. The mean size of the tumor was 10.6 mm. Four (7.4%) patients had not undergone axillary surgery, while thirty-eight (70.4%) had undergone sentinel lymph node biopsy and twelve (22.2%) had undergone axillary lymph node dissection (ALND). Significantly, four (33.3%) of those who had undergone ALND had tumor grade 2 (p = 0.020) and eight of them (66.7%) had ALNM. Fifty percent (50%) of patients who were treated with chemotherapy had grade 2 and multifocal tumors and ALNM. Moreover, the frequency of ALNM was higher in patients with tumor diameters greater than 10 mm. Median follow-up time was 80 months (12-220). None of the patients had locoregional recurrence, but one patient had systemic metastasis. Furthermore, five-year OS was 97.9%, while ten-year OS was 93.6%. Conclusion: PTBC is associated with favorable prognosis, good clinical outcomes and high survival rate, with rare recurrences and metastases.

Pushing the Limits of Breast-Conserving Surgery with Extreme Oncoplasty.

Introduction: We aimed to report the long-term surgical outcomes of extreme oncoplasty techniques in selected patients with unifocal (UF)/cT3 or multifocal-multicentric tumors (MFMC). Material and Methods: Patients who were initially recommended to have mastectomy underwent extreme oncoplastic breast-conserving surgery (eOBCS) including therapeutic reduction mammoplasty, racquet, and round-block mammoplasty, Grisotti flap, or combined technique were included. Preoperative tumor parameters, clinical outcomes, rate of local recurrence, survival, and patients' satisfaction were assessed. Results: Eighty-six patients with a median age of 51 years were followed for a median follow-up of 75 (8-154) months; 31 (36%) had cT3 and 55 (64%) had MFMC tumors. The majority of patients (83.6%) had invasive cancer. The median UF tumor size was 58 mm (range 51-100) on imaging and 51 mm (range 50-60) on final pathology. The median tumor span for MFMC was 65 mm (range 53-95) on imaging, whereas the median of the largest tumor size was 30 mm (range 22-60) on final pathology. Seventy-one patients (82.5%) were ER-positive, 17 (19.7%) were HER2 positive, and 8 (9.3%) were triple-negative breast cancer. Four patients (4.7%) required further intervention for having positive margins (3 re-excisions, 1 completion mastectomy). Three local recurrences (3.4%) and 10 (11.6%) distant metastasis occurred. The cosmetic outcome was excellent in 37 (43%) patients. No major complications were observed. Conclusions: eOBCS can be a good option for patients who initially require mastectomy. Appropriate patient selection, a multidisciplinary approach, and patient consent are essential steps of the procedure.

Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.

Diverging prognostic effects of CD155 and CD73 expressions in locally advanced triple-negative breast cancer.

Background: Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC). Methods: The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73. Results: Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24-239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005). Conclusion: These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.

Prognostic Implications of Immune Infiltrates in the Breast Cancer Microenvironment: The Role of Expressions of CTLA-4, PD-1, and LAG-3.

The assessment of immune infiltrate in invasive breast carcinomas (IBCs), most commonly referred to as tumor infiltrating lymphocytes (TILs), is gaining importance in the current quest for optimal biomarker selection and prediction of prognosis. In this study, the impact of intensity of TILs and expressions of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in a group of breast carcinomas with regards to the prognosis and conventional pathologic parameters was scrutinized. For this purpose, 238 patients with IBCs containing different proportions of TILs were included in the study. IBCs with higher proportion of TILs were usually grade III carcinomas and correlated with poor prognostic features like receptor negativity, nonluminal intrinsic subtype (P<0.001). Similarly, PD-1 and LAG-3 positivity in immune cells (IC) were more likely to be positive in grade III IBC cases (P=0.004). In addition, PD-1 positivity in IC was more frequent in estrogen receptor-negative tumors (P=0.011) whereas LAG-3 positivity increased in large sized, estrogen receptor and progesterone receptor-negative tumors (P=0.050, 0.023, 0.04, respectively). CTLA-4 positivity in IC was more frequent in large-sized tumors (P=0.040). These 3 markers were also significantly associated with one another and also with the amount of TILs. In survival analysis, cases with prominent-TILs especially displaying CTLA-4, PD-1, and LAG-3 positivity appeared to have longer disease-free and overall survival (CTLA-4: P=0.027, P=0.024; PD-1: P=0.030, P=0.026; LAG-3: P=0.006, P=0.012, respectively). We conclude that the high proportion of TILs and as well as high expression of CTLA-4, PD-1, and LAG-3 in TILs have positively contributed to the outcome despite their correlation with poor conventional pathologic features. We suggest that these 3 immune markers can be used for the determination of proper treatment as well as prediction of prognosis in IBCs with TILs.

SPECT/CT Lymphoscintigraphy Guidance Simplifies and Improves Targeted Axillary Dissection of the Clipped Nodes After Neoadjuvant Chemotherapy in Initially Node-Positive Breast Cancer.

PURPOSE: We assessed the feasibility of SPECT/CT lymphoscintigraphy ( 99m Tc-nanocolloid) method to simplify and improve targeted axillary dissection of clipped axillary lymph node (axLN) after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer. PATIENTS AND METHODS: Fifteen patients who had clip placement to biopsy-confirmed axLN metastasis due to clinically node-positive breast cancer before NAC and underwent SPECT/CT lymphoscintigraphy for surgery after NAC were included into the study. SPECT/CT lymphoscintigraphy was performed to localize the clipped node and to assess if the clipped lymph node (LN) had 99m Tc-nanocolloid uptake or not. In case the clipped node had no uptake on SPECT/CT, the patient was referred to wire-guided localization procedure. Blue dye was also injected for dual mapping of sentinel LN biopsy. RESULTS: All patients had only ipsilateral axLN metastasis. SPECT/CT lymphoscintigraphy showed that clipped LNs were radioavid in 12 of 15 patients (80%). Clipped LNs were not blue-stained in 5 patients (33.3%), and in 2 of them, clipped LNs were radioavid in SPECT/CT. Wire-guided localization was required in only 3 patients (20%) for nonradioavid/blue-stained clipped LNs. Removal of the clipped nodes was confirmed in all cases with a success rate of 100% by specimen graphy. CONCLUSION: SPECT/CT lymphoscintigraphy seems feasible to determine the clipped LNs intraoperatively without requiring additional invasive methods in most of the patients. This technique simplifies and improves targeted axillary dissection of the clipped axLNs after NAC in initially node-positive breast cancer and can be adapted to clinical practice with further investigations.

Ovarian and paraovarian adrenal rest tumors are not uncommon in gonadectomy materials of historical congenital adrenal hyperplasia cases in childhood.

Objective: The aim of this study was to assess the prevalence of ovarian and paraovarian adrenal rest tumors (ARTs) in gonadectomy materials of a subgroup of congenital adrenal hyperplasia (CAH) patients. Methods: A total of 20 historical cases with clinical/molecular diagnosis of classical CAH were included in the study. All patients had 46,XX karyotype and underwent gonadectomy because of being raised as male. Results: Median age at diagnosis of CAH was 5.7 years and was markedly delayed. All patients revealed severe virilization. Bone age was significantly advanced, and bone age/chronological age ratio was increased with a median ratio of 1.8. Median age at the time of gonadectomy was 9.2 years. Ovarian and paraovarian ARTs were detected during the pathological evaluation of gonadectomy materials in four patients (20%) (two with simple virilizing 21-hydroxylase and two with 11-beta-hydroxylase deficiency) with previously normal pelvic imaging. In three cases with ARTs, paraovarian area was composed of medium-sized polygonal cells, with round or oval monomorphic nuclei and abundant granular eosinophilic cytoplasm which is characteristic of adrenocortical tissue. The fourth case had bilateral ovarian 'steroid cell tumors, not otherwise specified', and the tumor was accepted as benign. Except for the ARTs, heterotopic prostate and bilateral paratubal epididymis tissue were detected in a patient. Conclusions: Ovarian and paraovarian ARTs might be more common than previously described, especially among patients with excessive and prolonged adrenocorticotropic hormone exposure. These tumors could be detected histopathologically even if not detected by classical imaging methods.

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases of PPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent of DICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.