Breast Reconstruction using the Anterior Approach Scarless Latissimus Dorsi Muscular flap: A Single Center Retrospective Study.

Introduction: Scarless latissimus dorsi (LD) flap is a breast reconstruction technique, which allow to cover the lower pole of implant with a large portion of the LD muscle without skin paddle; it represents a surgical solution that transpose vascularized tissue avoiding the failure of breast reconstruction, following necrosis of mastectomy skin flaps. Material and Method: A retrospective review of patients undergoing immediate or delayed breast reconstruction using scarless LD flap reconstructions was performed. Clinical data obtained from follow-up visits were recorded. To evaluate breast shape contentment and patient satisfaction, the patients were requested to answer the Breast-Q, version 2.0 reduction module postoperative scales questionnaire at the 12-month follow-up. Results: We performed 19 scarless LD flap reconstructions between September 2019 and June 2022. The surgical time in average (considering minutes ± SD) was 130 (±15) minutes. The aesthetic assessment was good/excellent in 83% of patients. This was statistically significant (P=0.0). Conclusions: The scarless LD flap reconstruction is a valid and reliable solution, which has the advantage to reduce the risk of exposed prosthesis if native skin necrosis occurs.

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.

Pleomorphic/solid lobular carcinoma of male breast with PALB2 germline mutation: case report and literature review.

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers and among these infiltrating lobular carcinomas (ILC) represents only 1-2% of all MBC cases. Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of ILC with only eight cases reported until now in males. Up to 10% of MBC cases have a germline pathogenic variant in a predisposing gene such as BRCA1 and BRCA2 genes. Mutations in PALB2 (partner and localizer of BRCA2) have been reported in men with breast cancer, with a frequency that ranges from 0.8 to 6.4%, but it has never been reported in male ILC. Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.

PD-L1 testing in metastatic triple negative breast cancer: Results of an Italian survey.

BACKGROUND: Immunotherapy has revolutionized the approach to metastatic triple-negative breast cancers. Atezolizumab was approved for patients with metastatic triple-negative breast cancers whose tumors express PD-L1, determined by SP 142 assay. To assess the availability and practice of SP142 test we administered a survey to all the 15 pathology departments of the Lazio Region during a six-month period. METHODS: The survey comprised 12 questions regarding the availability of SP142 in the pathology departments, the percentage of positive tests, the difficulties of pathologists in cases close to cut-off value and the tested samples. RESULTS: The SP142 assay was available in only eight centers. In case of positive result, most centers (5/8, 62.5%) reported values of PD-L1 expression ranging from > 1 to ⩽ 5%, with values close to the cut-off point (⩾ 1% or < 1%) being the greatest challenge.Most of the centers (6/8, 75%) tested material from both their own and other hospitals. In most centers, the evaluations were performed either on primary tumors or metastasis, in particular lymph nodes (5/8, 62.5%), followed by lung (3/8, 37.5%) and liver (1/8, 12.5%) metastasis. CONCLUSION: Our results raise some important issues concerning the evaluation of PD-L1 in the "real-life" setting, providing strategies for its implementation.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey.

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.

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.

Nipple-Sparing Mastectomy After Neoadjuvant Chemotherapy: Definitive Results with a Long-Term Follow-Up Evaluation.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used for women with breast cancer who are not candidates for conservative surgery. The authors previously reported satisfying results with NSM after neoadjuvant chemotherapy (NACT). METHODS: From 2010 to 2020, 1072 women underwent mastectomy at the authors' institution. In this group, 433 NSMs were performed (40%). The only contraindications to NSM were close proximity to the nipple-areola complex (NAC), bloody discharge, and Paget disease. RESULTS: In 112 cases involving 111 women, NSM followed NACT (group 1), whereas it was performed as primary surgery in 321 instances involving 306 women (group 2). At 5 years, local relapse was 7% in group 1 and 2% in group 2, although in the multivariate analysis, locoregional relapses (LRRs) did not differ between the two groups. An increased incidence of local relapse was associated with higher tumor stage (stage III; p = 0.046) and age younger than 51 years (p = 0.038). For 34 (30.3%) of the 111 women in group 1 with a pathologic complete response (pCR), no LRRs were recorded. Only one NAC recurrence was observed. Overall survival with each tumor stage did not differ between the two groups. No differences in complications were observed. Cosmetic results were satisfying in 83.8% of the cases and did not get worse after NACT. CONCLUSIONS: The study data definitively confirm that NSM is safe even after NACT, with good cosmetic results and complications comparable with those in the primary surgery setting. Tumor stage and age were the only independent factors for local relapse. Patients with pCR enjoyed optimal locoregional control.

An unusual case of extra-nodal interdigitating dendritic cell neoplasm: sarcoma or not?

INTRODUCTION: Interdigitating dendritic cell sarcoma (IDCS) represents an extremely rare neoplasm frequently originating from T-cell- associated dendritic antigen-presenting cells normally populating the paracortex of lymph nodes. Diagnosis is challenging due to the rarity of this neoplasm and the overlapping features with the other primary and metastatic spindle cell neoplasm, even more, when localized in an extra-nodal site. PATIENTS AND METHODS: Herein we report a case of 48 Years old woman with a six-month history of centimetric, quiet painful mass of the philtrum without other significant comorbidity. RESULTS: Histological report showed a proliferation of quiet bland spindle to plump cell, scattered multinucleated giant cell in a subtle background of lymphocytes. IHC study displays only positivity for S-100 and fine, granular scattered cytoplasmatic stain for CD68; all dendritic IHC markers were negative. Morphological and immunohistochemical analyses were consistent with extra-nodal Interdigitating Dendritic Cell Neoplasm. CONCLUSION: Interdigitating Dendritic Cell Sarcoma is a rare and challenging entity with a variable prognosis. We present a case of extra-nodal IDCS whit low worrisome histological features, emphasizing the need for further efforts to better definitely this rare neoplasm ad its potential for malignancy.

Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis.

BACKGROUND: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases. METHODS: Syndecan-1 expression was determined by immunohistochemistry. Focal vs diffuse (< or > 50% of cancer cells, respectively) pattern of expression, cellular localization (cytoplasm vs membrane) and intensity of immunostaining on neoplastic cells were evaluated. Moreover, the extent and pattern of expression of syndecan-1 were compared between primary tumors and paired metastases and correlated with the tumor intrinsic subtype. RESULTS: A total of 23 cases, 10 with paired primary and metastatic tumor and 13 brain metastases, were evaluated. Syndecan-1 was expressed in both primary and metastatic BC. A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process. Concerning the extent of expression, we observed in metastatic lesions, a trend of association between intrinsic subtypes and extent of positivity. In particular, both BC characterized by overexpression of HER2 and triple-negative tumors were correlated with a diffuse pattern of expression with a moderate to strong intensity. CONCLUSION: A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process.

Central mucoepidermoid carcinoma of the mandible deriving from odontogenic cyst: A case report and review of the literature.

Mucoepidermoid Carcinoma (MEC) it can origin from a mandibular odontogenic cyst. We report the case of a 63-year-old man with MEC of the right retromolar trigonum of the mandibula. We performed a wide mandibular excision and immediate reconstruction with a fibula bone free flap.

Pathological examination of breast cancer samples before and after neoadjuvant therapy: recommendations from the Italian Group for the Study of Breast Pathology - Italian Society of Pathology (GIPaM-SIAPeC).

Neoadjuvant therapy (NAT) in breast cancer is administered to downstage the tumor, de-escalate surgery, and provide prognostic information that can be used to tailor subsequent adjuvant therapy. In this respect, the pathological evaluation of both pre-NAT biopsies and post-NAT surgical specimens is crucial to precisely assess the treatment response. With the increasing possibilities of NAT protocols and the rising number of eligible patients, it has become extremely important to standardize the pathological response assessment. Here, we provide an update on the recommendations of the Italian Group for the Study of Breast Pathology - the Italian Society of Pathology (GIPaM-SIAPeC) for the analysis of breast cancer samples before and after NAT.

Large cervical mass and head and neck cancer. First report of ectopic papillary adenoma of the lung.

AIM: We aim to report the first case of ectopic papillary adenoma of the lung (PAL), identified in the neck. METHODS: A 62-year-old woman with a known history of thyroid cancer treated several years ago, presented at our department because affected by an unpainful latero-cervical neck mass. The patient performed neck ultrasound echography, blood tests and computed tomography (CT) of head, neck and thorax to exclude the recurrence of the thyroid tumor or other unknown cancer of head and neck. RESULTS: Her CT with contrast identified a large mass in the left thyroid loggia, with well-defined margins without post-contrast enhancement; the mass laterally displaced the trachea, without reduction of airways caliber. The tumor was removed. The histologic analysis showed aspects typical of PAL. Because the mass was completely removed, and no lymph nodes were identified, additional treatments were excluded. CONCLUSIONS: Despite the ectopic tissue can be rarely identified in the neck, it should be always considered because it might degenerate and cause, as in our case, a tumor like PAL. The diagnostic plan is fundamental to well manage latero-cervical mass avoiding risks for patients.

Cribriform adenocarcinoma of the tongue and minor salivary glands: a systematic review of an uncommon clinicopathological entity.

INTRODUCTION: Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a rare neoplasm, accounting for less than 1% of salivary gland tumors. In the past it has been considered a possible variant of polymorphous low-grade adenocarcinoma (PLGA), while nowadays it is accepted as a provisional entity in the WHO classification. The aim of this paper is to systematically review the existing literature about CATMSG with a particular attention to differential diagnosis and prognostic factors. METHODS: This study was performed in accordance with the PRISMA checklist. A comprehensive search in PubMed, Cochrane, and Google Scholar databases was carried out in June 2021, in partnership with a medical librarian, without time restriction. Search items include the following keywords: "cribriform adenocarcinoma of the tongue" OR "cribriform adenocarcinoma of the tongue and minor salivary glands." RESULTS: A total of 56 patients were evaluated. Patient age across the studies ranged from 13 to 85 years (mean 59.6 year). The most common site of involvement was the tongue (58.9%), followed by palate (19.6%), tonsil (7.1%), buccal (3.6%) and reticular mucosa (3.6%), lip (3.6%), retromolar pad (1.7%), and floor of the mouth (1.7%). Lymph node involvement at the diagnosis was very common (58.9%), while there was no evidence of patients diagnosed with metastatic disease. The most common surgical approach was surgical excision (17, 30.3%); neck dissection was performed in 16 patients (28%). Radiotherapy was the most common adjuvant treatment reported (46.4%); only one patient underwent adjuvant chemotherapy (1.7%). Five patients experienced a recurrence (8.8%). CONCLUSION: To our knowledge, only 56 five cases of CATMSG have been previously described. The results of this review seem to confirm the low frequency of relapses and distant metastases, but we observed that almost 60% of cases presented with cervical lymph node involvement. In our opinion, CATMSG should be considered as a distinct tumor entity from PLGA.

Evaluating programmed death-ligand 1 (PD-L1) in head and neck squamous cell carcinoma: concordance between the 22C3 PharmDx assay and the SP263 assay on whole sections from a multicentre study.

AIMS: The introduction of immunotherapy for patients with head and neck squamous cell carcinoma (HNSCC) raises the need for harmonisation between different types of antibody and immunohistochemistry platform for evaluating the expression of PD-L1 by use of the combined positive score (CPS) in this tumour. The aim of this study was to compare the expression of PD-L1 as determined with the CPS and two widely used assays (the 22C3 PharmDx assay and the SP263 assay) in a cohort of HNSCCs. METHODS AND RESULTS: We analysed 43 whole sections of HNSCC with two different anti-PD-L1 antibodies, 22C3 and SP263. The results, expressed as the CPS, were evaluated by 10 trained pathologists and statistical analyses were performed. We found a very similar results for PD-L1 expression between the 22C3 PharmDx assay and the SP263 assay in our cohort, and a strong and significant correlation between the two assays for all specimens (P < 0.0001). The interobserver reliability among pathologists for the continuous scores of CPS with the intraclass correlation coefficient and the correlation between the two assays were both good. Moreover, the rate of agreement between assays was high at all cut-offs and was best for the most relevant cut-off of CPS ≥ 1, and the kappa values were always in the range of almost perfect. CONCLUSIONS: Two different assays (the 22C3 PharmDx assay and SP263 assay) for PD-L1 in HNSCC showed high agreement. These data suggest that these two assays are interchangeable in the selection of patients with HNSCC for immunotherapy.

Cribriform adenocarcinoma of the tongue with cervical lymph nodes involvement: Report of an extremely rare tumor and focus about differential diagnosis with polymorphous adenocarcinoma.

Cribriform adenocarcinoma is a rare tumor that arise in tongue and minor salivary glands. Previously, only 56 case have been described. In this paper, we report a case of a 83-year-old man and we focus about the differential diagnosis with polymorphous adenocarcinoma.

Intramedullary Spinal Cord Metastasis Mimicking Astrocytoma: A Rare Case Report.

Intramedullary spinal cord metastases (ISCMs) are infrequent lesions. Their incidence is estimated to range from 0.9 to 2.1%, found in autopsies of cancer patients. However, as the life expectancy of malignant tumour patients constantly increases, the reported incidences of ISCMs are consequently rising. This report presents a case of the misdiagnosis of an anaplastic astrocytoma type of tumour due to its similarities to small-cell neuroendocrine carcinoma. Therefore, we would like to underline the importance of further investigation that could assist and support the surgeon in the making of the differential diagnosis. We present the clinical case of a 73-year-old woman with a solitary intramedullary spinal cord metastasis as the initial manifestation of a carcinoid type of tumour. The patient was admitted to our department while presenting a rapid onset of paraparesis. Magnetic resonance imaging was performed, which showed an intramedullary mass at the C2-C6 vertebral level with a heterogeneous contrast enhancement. In light of these findings, the patient underwent surgery for a partial tumour resection. The lesion resulted in being a small-cell neuroendocrine type of carcinoma. This peculiar type of tumour presents similar radiological characteristics to the anaplastic astrocytoma type, which is why our diagnostical mismatch occurred. This is the report of a rare case of solitary intramedullary spinal cord metastasis, which is the result of an initial presentation of a lung small-cell neuroendocrine type of carcinoma. We conclude that ISCMs should be regularly considered as a part of the differential diagnosis of intramedullary lesions, especially in the case of a rapid onset and deterioration of neurological symptoms.