Clipping a Positive Lymph Node Improves Accuracy of Nodal Staging After Neoadjuvant Chemotherapy for Breast Cancer Patients, but Does It Drive Management Changes?

BACKGROUND: Sentinel lymph node (SLN) biopsy for cN+ breast cancer patients after neoadjuvant chemotherapy (NAC) is controversial because the false-negative rate (FNR) is high. Identification of three or more SLNs with a dual tracer improves these results, and inclusion of a clipped lymph node (CLN) (targeted axillary dissection [TAD]) may be even more effective. METHODS: A retrospective, single-institution analysis of consecutive cN+ patients undergoing NAC from 2019 to 2021 was performed. Patients routinely underwent placement of a clip in the positive lymph node before NAC, and TAD was performed after completion of therapy. RESULTS: The study analyzed 73 patients, and the identification rate for CLN was 98.6% (72/73). A complete response in the lymph nodes was achieved for 43 (59%) of the 73 patients. Overall, the CLN was not a SLN in 18 (25%) of 73 cases, and for women who had one or two and those who had three or more SLNs identified, this occurred in 11 (32%) and 7 (21%) of 34 cases, respectively. Failure of SLN or TAD to identify a positive residual lymph node status after NAC occurred in 10 (15%) of 69 and 2 (3%) of 73 cases, respectively (p = 0.01). In four cases, a SLN was not retrieved (5.5%), and two of these cases had a positive CLN. In three cases, the CLN was the only positive node and did not match with a SLN, directing lymphadenectomy and oncologic management change in two cases. Therefore, 7 (10%) of 73 cases had a change in surgical or oncologic management with TAD. CONCLUSIONS: For a conservative axillary treatment in this setting, TAD is an effective method. It is more accurate than SLN alone and allows management changes. Further studies are warranted.

Metastatic upper tract urothelial carcinoma with nest-like features presenting as malignant pleural effusion.

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest-old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small-to-large clusters, and raspberry-like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest-like structures. The tumor cells showed a high nuclear-to-cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest-like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working-up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis.

Histologic findings at diagnosis as predictive markers of clinical outcome in pediatric ulcerative colitis.

BACKGROUND: The role of histological inflammation at diagnosis as a possible prognostic factor for disease course has not been investigated. AIMS: To assess whether histologic findings at diagnosis could predict clinical outcomes and evaluate the association between clinical, biochemical, endoscopic, and histological findings. METHODS: Prospective single-center study including pediatric UC patients with a minimum follow-up of 12 months. The association between histological activity (Nancy Index, Robarts Histopathology Index, and Geboes Score) and 12-month clinical outcomes was evaluated. Secondarily, we assessed the correlation between histological scores and endoscopic and inflammatory markers at the diagnosis. Inter-observer agreement for histologic and endoscopic scores was also evaluated. RESULTS: Forty-nine UC patients were included. No association was found between 1-year clinical relapse and the three histological indices at diagnosis (p > 0.05). Good concordance was found among the three histological scores (p < 0.001), and between all histological and endoscopic indices (p < 0.05). No correlation was found between histologic scores and serum inflammatory markers. Inter-observer agreement was good for eMayo, Nancy and Robarts score (k = 0.71, k = 0.74 and k = 0.68, respectively) and moderate for Geboes (k = 0.46). CONCLUSIONS: Histological findings at diagnosis cannot be used as a predictor of the disease course. The three histological scores used in routine clinical practice show an overall good correlation and reliability.

Laterocervical lymph node metastases from suspected thyroidal primary site that turned out to be metastases of lung cancer: A case report.

Incidental sonographic discovery of thyroid nodules is an increasingly common event in clinical practice. Less frequently, patients with cytological benign thyroid nodules have suspicious cervical lymph nodes detected by ultrasound examination or by cytological exam. Here, we discuss an intriguing case of cervical lymph node metastasis with a probable thyroid origin in a 65-year-old asymptomatic male smoker. He underwent thyroidectomy and unilateral cervical lymphadenectomy. Despite a negative chest X-ray, the postoperative histological examination revealed that the lymph node metastasis was actually from a lung carcinoma. Metastatic lesions in cervical lymph nodes from non-thyroidal origins must be excluded when evaluating lesions in the region, especially when thyroid nodules subjected to fine needle aspiration biopsy yield negative results, or lymph node cytological evaluations are inconsistent with thyroid cytological findings and sonographic features. Thyroid and lung adenocarcinomas share some epithelial and mesenchymal markers. Thyroglobulin helps differentiate primary thyroid tumors from lung ones, but in cases of poor differentiation, distinguishing metastatic lesions in the thyroid gland can be challenging. Lung cancer (LC) is the leading cause of cancer mortality worldwide, and survival rates have only marginally improved over the last several decades. The ongoing clinical challenge is detecting LC at earlier stages of the disease.

Intraoperative Examination of Retro-Areolar Margin is not Routinely Necessary During Nipple-Sparing Mastectomy for Cancer.

BACKGROUND: Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real advantage. METHODS: Consecutive patients undergoing NSM for cancer with omission of IERM according to institutional protocols from 2016 to 2021 were retrospectively analyzed. The decision to maintain or remove the Nipple-Areola Complex (NAC) after definitive pathology was taken at the multidisciplinary meeting. RESULTS: Among 162 women operated in the study period, the presence of neoplastic cells within 2 mm from the inked retroareolar margin (RAM) was detected at permanent pathology in 17 cases (10.5%). Nipple-Areola-Complex (NAC) was removed postoperatively in five patients (3%) for margins <1 mm, the other 12 were observed, whereas postoperative NAC necrosis required surgical removal in additional five cases (3%). The NAC was thus preserved in 152 of 162 patients (94%). At multivariate analysis, RAM ≤2 mm was associated with radiological tumor-to-nipple distance less than or equal to 1 cm (p = 0.04) and Ki67 label index ≥ 20 (p = 0.04), whereas multifocality/multicentricity showed a trend towards significance (p = 0.07). At a median follow-up of 46 months, five locoregional relapses occurred (3%), only one of them involving the NAC (0, 6%). Locoregional relapse and overall survival for patients with RAM > or < 2 mm were not different. CONCLUSIONS: IERM is not routinely necessary during NSM for cancer, because its omission is associated with a very low return to the operating room, it is oncologically safe, and associated pitfalls are avoided. Further studies are necessary to confirm these findings.

Syphilis, the Great Imitator-Clinical and Dermoscopic Features of a Rare Presentation of Secondary Syphilis.

Syphilis is characterized by a wide range of variable clinical symptoms; therefore, it is often referred to as "The Great Imitator". Here, we report the case of a 69-year-old hepatitis-C-positive MSM patient, who was admitted to our clinic due to a solitary firm painless erythematous maculopapular lesion with a central crater-like crust on the upper right thigh that occurred two months prior. The dermoscopy showed an erythematous, copper-colored, oval lesion with diffuse monomorphic dotted and glomerular vessels, central crust, and circular scaling (Biett's sign). The histological findings ruled out neoplasia and described a plasma cell infiltrate and endothelial swelling. Finally, the combination of the dermoscopic image, histological findings and the additionally acquired knowledge about the sexual history of the patient at the second visit led to the diagnosis, which was then confirmed with serological tests. Dermoscopy may become a supportive tool to facilitate the recognition of secondary syphilis; however, the reporting of these atypical cases is crucial to highlight the many faces of the disease so that clinicians consider syphilis as part of the differential diagnosis of non-specific lesions.

Chemo-surgical approach in vulvar leiomyosarcoma: A case report.

INTRODUCTION: Primary sarcoma of the vulva is an extremely rare entity, representing only 1%-3% of all vulvar malignant neoplasms. Among sarcomas, leiomyosarcoma (LMS) is the most prevalent histologic variant. Due to the rarity of LMS, guidelines are lacking and phase III trials have not been carried out, so clinical management is based on local clinical practice and physician experience. CASE PRESENTATION: Here, we described a case of primary LMS of the vulva and its successful management, with the adoption of neoadjuvant chemotherapy and surgery. We report a case of a 74-year-old woman with 12.5 cm vulvar LMS. The patient received three cycles of neoadjuvant chemotherapy with a partial response. Radical vulvectomy with vulvar reconstruction with V-F flap was carried out. Surgical margins were negative. Three additional cycles of adjuvant chemotherapy were delivered. RESULTS: One year after treatment, the patient was disease-free. CONCLUSION: There are no approved therapeutic protocols for this rare neoplasia. Surgery is the mainstay of treatment. However, it is not always feasible, so neoadjuvant chemotherapy was delivered for downstaging the vulvar lesion. We suppose that neoadjuvant chemotherapy has optimized the possibilities of radical surgery. Despite the anectodical nature of this case presentation, neoadjuvant chemotherapy seems a valid therapeutic option for managing patients with bulky vulvar sarcoma. Further large collaborative studies are warranted to identify the best therapeutic option for these patients.

Sporadic diffuse neurofibroma of the retropharyngeal space.

Neurofibroma (NF) rarely arises in the retropharyngeal space (RPS) of patients with or without Neurofibromatosis type I (NF-I). The diffuse subtype of NF (DNF) is characterized by an infiltrative growth pattern and typically involves the skin and subcutaneous tissue of the head and neck. We describe the clinic-pathologic features of a DNF involving the RPS of an adult without NF-I. To date, this subtype of NF has never been reported at this site.

Autophagy occurs in lymphocytes infiltrating Sjögren's syndrome minor salivary glands and correlates with histological severity of salivary gland lesions.

BACKGROUNDS: The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren's syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression. METHODS: After collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC). RESULTS: Real-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30). CONCLUSIONS: In SS MSG, lymphocytes' autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions.

CXCL13 as biomarker for histological involvement in Sjögren's syndrome.

OBJECTIVES: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. METHODS: 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects' (n = 19) sera were used as control. RESULTS: CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. CONCLUSION: Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren's Syndrome: Association with Disease Susceptibility and Clinical Aspects.

Sjögren's syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with interesting results. We investigated the association between the STAT4, TRAF3IP2, HCP5, and IL10 polymorphisms and SS susceptibility and their possible role in the modulation of clinical and laboratory features. 195 consecutive patients with SS were enrolled and clinical and laboratory data were collected. 248 age- and sex-matched healthy subjects were used as controls. Genotyping was performed by allelic discrimination assays. A case-control association study and a phenotype-genotype correlation analysis were performed. A genetic risk profile was developed considering the risk alleles. Both the variant alleles of rs7574865 in the STAT4 gene and rs3099844 in the HCP5 gene were significantly more prevalent in patients than in controls (OR = 1.91 and OR = 2.44, respectively). The variant allele of rs3024505 of IL10 resulted to be a susceptibility allele (OR = 1.52), while the variant allele of rs1800872 seemed to confer a protective effect for the development of the disease (OR = 0.65). A risk genetic profile showed a higher probability to develop the disease in subjects with at least three risk alleles; subjects with 4 risk alleles were not observed in the controls. HCP5 rs3099844 was associated with anti-SSA (P = 0.006, OR = 3.07) and anti-SSB (P = 0.005, OR = 2.66) antibodies, severity of focus score (P = 0.03, OR = 12), and lymphoma development (P = 0.002, OR = 7.23). Patients carrying the STAT4 rs7574965 variant allele had a higher risk of monoclonal component and leukopenia (P = 0.002, OR = 7.6; P = 0.048, OR = 2.01, respectively). We confirmed the association of SS with the STAT4 and IL10 genes and we describe a novel association with HCP5. In particular, we describe an association of this specific SNP of HCP5 not only with disease development but also with autoantibody production and focus score suggesting a potential contribution of this variant to a more severe phenotype.