Optimising the Early-Stage Rehabilitation Process Post-ACL Reconstruction.

Outcomes following anterior cruciate ligament reconstruction (ACLR) need improving, with poor return-to-sport rates and a high risk of secondary re-injury. There is a need to improve rehabilitation strategies post-ACLR, if we can support enhanced patient outcomes. This paper discusses how to optimise the early-stage rehabilitation process post-ACLR. Early-stage rehabilitation is the vital foundation on which successful rehabilitation post-ACLR can occur. Without high-quality early-stage (and pre-operative) rehabilitation, patients often do not overcome major aspects of dysfunction, which limits knee function and the ability to transition through subsequent stages of rehabilitation optimally. We highlight six main dimensions during the early stage: (1) pain and swelling; (2) knee joint range of motion; (3) arthrogenic muscle inhibition and muscle strength; (4) movement quality/neuromuscular control during activities of daily living (5) psycho-social-cultural and environmental factors and (6) physical fitness preservation. The six do not share equal importance and the extent of time commitment devoted to each will depend on the individual patient. The paper provides recommendations on how to implement these into practice, discussing training planning and programming, and suggests specific screening to monitor work and when the athlete can progress to the next stage (e.g. mid-stage rehabilitation entry criteria).

An Innovative Technique for Ejaculation-Sparing Prostatic Enucleation with Thulium:YAG Laser.

Purpose: We report our experience with 100 patients who underwent an innovative prostate enucleation technique that spares the complete urethral-plate from the veru montanum to the bladder neck using a low-energy thulium laser emission. The aim of our study was to evaluate the short-term effects of this procedure on ejaculation preservation and urinary obstruction. Materials and Methods: The International Prostate Symptom Index (IPSS), quality of life (QoL), and Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EJD) Short Form were used as validated instruments to quantify ejaculatory dysfunction before and 6 months after the surgery. Results: The median IPSS score pre- and postoperatively was 20 and 5, respectively (p < 0.0001); QoL dropped from a median of 4-1 (p < 0.0001); and the mean preoperative maximal flow rate improved significantly (8.5 vs 21.2 mL/min) (p < 0.0001). Furthermore, there was significant reduction in postvoid residual postoperatively (p < 0.0001). Postoperative ejaculatory function was preserved in 92/100 patients (92%). According to the MSHQ-EJD score, patients reported a slight nonsignificant decrease in frequency of ejaculation (item 1), force of expulsion (item 2) and reduction in semen volume during ejaculation (item 3), with the exception of ejaculation discomfort (item 4). Conclusion: According to our results, complete removal of the apical tissue, which has been advocated as an integral part of the so called ejaculatory hood, does not interfere with ejaculation if the ventral lissosphincter remains intact.

Immunohistochemical Markers and TILs Evaluation for Endometrial Carcinoma.

OBJECTIVE: The molecular classification for endometrial cancer (EC) introduced by The Cancer Genome Atlas Research Network (TCGA) and the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) proved the existence of four molecular prognostic subtypes; however, both classifications require costly technology. We suggest a prognostic model for EC based on immunohistochemistry (IHC) and tumor-infiltrating lymphocytes (TILs). STUDY DESIGN: One hundred patients were included. We retrospectively investigated IHC prognostic parameters: mismatch repair (MMR)-deficient tumors, p53 mutation status, progesterone receptors (PgRs), and estrogen receptors (ERs). We further evaluated TILs. These parameters were related to the clinical and morphological features and to the outcome. RESULTS: We classified tumors into three groups (IHC analysis): MMR-deficient, p53-mutated, p53 wild-type. MMR-deficient tumors had a good prognosis, p53 wild-type tumors an intermediate one, and p53-mutated tumors had the poorest outcomes. Disease-free (DFS) and overall survival (OS) were significantly better among PgR+ tumors (respectively p = 0.011 and p = 0.001) and PgR expression is an independent prognostic factor for a better DFS frommultivariate analysis (OR = 0.3; CI: 0.1-0.9; p = 0.03).No significant correlation was observed between DFS and TILs. However, among MMR-deficient tumors, the mean value of TILs was higher than among the other tumors(111 versus 71, p = 0.01) Conclusions: The prognostic model based on IHC markers could potentially be a valid and applicable alternative to the TCGA one. The PgR determination could represent an additional prognostic factor for EC.

A Multi-Class Approach for the Automatic Detection of Congestive Heart Failure in Windowed ECG.

Congestive heart failure (CHF) is a chronic heart disease that causes debilitating symptoms and leads to higher mortality and morbidity. In this paper, we present HARPER, a novel automatic detector of CHF episodes able to distinguish between Normal Sinus Rhythm (NSR), CHF, and no-CHF. The main advantages of HARPER are its reliability and its capability of providing an early diagnosis. Indeed, the method is based on evaluating real-time features and observing a brief segment of ECG signal. HARPER is an independent tool meaning that it does not need any ECG annotation or segmentation algorithms to provide detection. The approach was submitted to complete experimentation by involving both the intra- and inter-patient validation schemes. The results are comparable to the state-of-art methods, highlighting the suitability of HARPER to be used in modern IoMT systems as a multi-class, fast, and highly accurate detector of CHF. We also provide guidelines for configuring a temporal window to be used in the automatic detection of CHF episodes.

Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients.

BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line. METHODS: Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues. RESULTS: We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed. CONCLUSIONS: This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.

Adrenal Rests in the Uro-genital Tract of an Adult Population.

Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.

Could a 2D/3D US based model be helpful in the assessment of myometrial invasion at time of intraoperative frozen section? A pilot study.

BACKGROUND: The assessment of myometrial invasion is a pivotal step in the preoperative staging of endometrial cancer. Intraoperative frozen section (FS) represents a reliable tool in directing surgeon's choices. Preoperative transvaginal ultrasound (US) showed high accuracy in evaluating myometrial invasion. This study aimed to understand if the application of a standardized ultrasonographic protocol for the pre-operative evaluation of myometrial invasion can help pathologists in improving the accuracy of FS. Furthermore, the agreement between US and FS in the assessment of myometrial invasion was assessed. METHODS: Sixty-six patients who underwent surgery for endometrial cancer were analyzed. Preoperative 2D/3D ultrasound was performed in all the patients. Myometrial invasion was estimated by subjective assessment and objective measurement techniques. Data from US were reported to pathologists through a prefilled form with depth and site of the maximum myometrial invasion. Diagnostic performance of US and FS were compared having the definitive histological examination as the gold standard. RESULTS: Influenced by the information given by our 3D US-model, FS showed a 90% sensitivity and a 93% specificity, with a 93% PPV and an 89% NPV. The agreement with histology was strong (K=0.824). Myometrial invasion was missed at the level of the isthmus by FS just in one case. Subjective assessment was confirmed as the most reliable ultrasonographic technique in assessing myometrial invasion, with 90% sensitivity, 78% specificity, 80% PPV and 89% NPV. The agreement with histology was substantial (K=0.68). CONCLUSIONS: The application of a preoperative 2D/3D US assessment would seem to help pathologists in detecting myometrial invasion in difficult areas of the uterus such as the isthmus, reducing downstaging and overtreatment.

Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S(+)-ibuprofen.

S(+)-ibuprofen (S-IBU) and R(-)-ibuprofen (R-IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of therapy (three intravenous doses of 10-5-5 mg kg-1 at 24-h intervals), at the end of the first infusion and 6, 24, 48, and 72 h later. Data were analyzed with a PK model that included enantiomer elimination rate constants and the R- to S-IBU conversion rate constant. The T½ of S-IBU in the newborn was much longer than in adults (41.8 vs. ≈2 h), whereas the T½ of R-IBU appeared to be the same (2.3 h). The mean fraction of R- to S-IBU conversion was much the same as in adults (0.41 vs. ≈0.60). S-IBU concentrations measured 6 h after the first dose were higher than at the end of the infusion in 10 out of 16 cases, and in five cases, they remained higher even after 24 h. This behavior is unprecedented and may be attributable to a rapid R-to-S conversion overlapping with a slow S-IBU elimination rate. In 13 of the 16 neonates, S-IBU concentrations at 48 and/or 72 h were lower than expected, probably due to the rapid postnatal maturation of the newborn's liver metabolism.

Recommendations for Hamstring Function Recovery After ACL Reconstruction.

It is important to optimise the functional recovery process to enhance patient outcomes after major injury such as anterior cruciate ligament reconstruction (ACLR). This requires in part more high-quality original research, but also an approach to translate existing research into practice to overcome the research to implementation barriers. This includes research on ACLR athletes, but also research on other pathologies, which with some modification can be valuable to the ACLR patient. One important consideration after ACLR is the recovery of hamstring muscle function, particularly when using ipsilateral hamstring autograft. Deficits in knee flexor function after ACLR are associated with increased risk of knee osteoarthritis, altered gait and sport-type movement quality, and elevated risk of re-injury upon return to sport. After ACLR and the early post-operative period, there are often considerable deficits in hamstring function which need to be overcome as part of the functional recovery process. To achieve this requires consideration of many factors including the types of strength to recover (e.g., maximal and explosive, multiplanar not just uniplanar), specific programming principles (e.g., periodised resistance programme) and exercise selection. There is a need to know how to train the hamstrings, but also apply this to the ACLR athlete. In this paper, the authors discuss the deficits in hamstring function after ACLR, the considerations on how to restore these deficits and align this information to the ACLR functional recovery process, providing recommendation on how to recover hamstring function after ACLR.

Rare case of uterine cervix lymphoma with spontaneous regression: Case report.

Primary malignant lymphoma rarely occurs in the female reproductive tract, because of that they are often misdiagnosed. Lymphoma spontaneous regression is even rarer, but it is possible behavior of this disease. A case of 54-year-old female patient with a primary diffuse large B-cell lymphoma of the cervix is presented. First assumption was sarcoma or atypical adenocarcinoma; biopsies have been inconclusive and, after a partial spontaneous regression, diagnosis of lymphoma was possible only after surgery. The diagnosis was a real challenge for clinicians, radiologists and pathologists for both localization and behavior. Difficulties in diagnosis led to an over-treatment: a laparotomic bilateral hysteron salpingectomy with lymphadenectomy was performed, while chemotherapy alone would have been the right approach. Considering that prognosis and treatment of primary malignant lymphoma of the cervix are completely different than those of other malignant tumors of the uterus, this disease should be considered in the differential diagnosis.

Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?

In previous studies, steady-state Z-endoxifen plasma concentrations (ENDOss) correlated with relapse-free survival in women on tamoxifen (TAM) treatment for breast cancer. ENDOss also correlated significantly with CYP2D6 genotype (activity score) and CYP2D6 phenotype (dextromethorphan test). Our aim was to ascertain which method for assessing CYP2D6 activity is more reliable in predicting ENDOss. The study concerned 203 Caucasian women on tamoxifen-adjuvant therapy (20 mg q.d.). Before starting treatment, CYP2D6 was genotyped (and activity scores computed), and the urinary log(dextromethorphan/dextrorphan) ratio [log(DM/DX)] was calculated after 15 mg of oral dextromethorphan. Plasma concentrations of TAM, N-desmethyl-tamoxifen (ND-TAM), Z-4OH-tamoxifen (4OH-TAM) and ENDO were assayed 1, 4, and 8 months after first administering TAM. Multivariable regression analysis was used to identify the clinical and laboratory variables predicting log-transformed ENDOss (log-ENDOss). Genotype-derived CYP2D6 phenotypes (PM, IM, NM, EM) and log(DM/DX) correlated independently with log-ENDOss. Genotype-phenotype concordance was almost complete only for poor metabolizers, whereas it emerged that 34% of intermediate, normal, and ultrarapid metabolizers were classified differently based on log(DM/DX). Multivariable regression analysis selected log(DM/DX) as the best predictor, with patients' age, weak inhibitor use, and CYP2D6 phenotype decreasingly important: log-ENDOss = 0.162 - log(DM/DX) × 0.170 + age × 0.0063 - weak inhibitor use × 0.250 + IM × 0.105 + (NM + UM) × 0.210; (R2  = 0.51). In conclusion, log(DM/DX) seems superior to genotype-derived CYP2D6 phenotype in predicting ENDOss.

Neuroendocrine breast carcinoma: a rare but challenging entity.

Breast carcinoma with neuroendocrine differentiation, also known as neuroendocrine breast carcinoma (NEBC), includes a heterogeneous group of rare tumors, which account for 2-5% of all invasive breast carcinomas. Because of their low incidence, most of the current limited knowledge of these tumors derives from anecdotal case reports or small retrospective series. The diagnosis of NEBC is based on the presence of morphological features similar to gastrointestinal and lung NETs and neuroendocrine markers. NEBCs are usually hormone receptors positive and HER2 negative, but despite this luminal phenotype, most recent studies suggested that NEBC could be associated with worse prognosis compared to invasive breast cancer without neuroendocrine differentiation. Due to its rarity and lack of randomized data, there is little evidence to guide the choice of treatment, so NEBC is currently treated as any invasive breast carcinoma not-otherwise specified. Recently, attempts to molecularly characterize NEBC have been made, in order to provide new targets for a more personalized treatment of this uncommon entity.

A Clinically Applicable Approach to the Classification of B-Cell Non-Hodgkin Lymphomas with Flow Cytometry and Machine Learning.

The immunophenotype is a key element to classify B-cell Non-Hodgkin Lymphomas (B-NHL); while it is routinely obtained through immunohistochemistry, the use of flow cytometry (FC) could bear several advantages. However, few FC laboratories can rely on a long-standing practical experience, and the literature in support is still limited; as a result, the use of FC is generally restricted to the analysis of lymphomas with bone marrow or peripheral blood involvement. In this work, we applied machine learning to our database of 1465 B-NHL samples from different sources, building four artificial predictive systems which could classify B-NHL in up to nine of the most common clinico-pathological entities. Our best model shows an overall accuracy of 92.68%, a mean sensitivity of 88.54% and a mean specificity of 98.77%. Beyond the clinical applicability, our models demonstrate (i) the strong discriminatory power of MIB1 and Bcl2, whose integration in the predictive model significantly increased the performance of the algorithm; (ii) the potential usefulness of some non-canonical markers in categorizing B-NHL; and (iii) that FC markers should not be described as strictly positive or negative according to fixed thresholds, but they rather correlate with different B-NHL depending on their level of expression.

DOAC plasma levels measured by chromogenic anti-Xa assays and HPLC-UV in apixaban- and rivaroxaban-treated patients from the START-Register.

INTRODUCTION: To measure direct factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) concentrations, dedicated chromogenic anti-Xa assays are recommended as suitable methods to provide rapid drug quantification. Moreover, the high-performance liquid chromatography with ultraviolet detection (HPLC-UV) is reported as a reliable quantitative technique. We investigated seven anti-Xa assays and an HPLC-UV method for measurement of apixaban and rivaroxaban levels in patients enrolled in the START-Register. METHODS: A total of 127 apixaban and 124 rivaroxaban samples were tested by HPLC-UV and the following anti-Xa assays: Biophen DiXaI and Heparin LRT (Hyphen BioMed), Berichrom and Innovance Heparin (Siemens), STA-Liquid Anti-Xa (Stago Diagnostics), Technochrom anti-Xa (Technoclone), and HemosIL Liquid Anti-Xa (Werfen). Each method was performed in one of the participating laboratories: Bologna, Cremona, Florence, and Padua. RESULTS: Our data confirmed the overestimation of apixaban and rivaroxaban levels by the antithrombin-supplemented anti-Xa method (Berichrom). Performances and reproducibility of the six anti-Xa assays not supplemented with antithrombin and the HPLC-UV method were good, with limits of quantification from 8-39 ng/mL (apixaban) and 15-33 ng/mL (rivaroxaban). The six chromogenic methods showed good concordances with the quantitative HPLC-UV [bias: -26.9-22.3 ng/mL (apixaban), -11.3-18.7 ng/mL (rivaroxaban)]. Higher bias and wider range between limits of agreement were observed at higher concentrations [<100 ng/mL: bias -21.3-4.1 ng/mL (apixaban) and -6.2-3.8 ng/mL (rivaroxaban); >200 ng/mL: bias -42.2-36.8 ng/mL (apixaban) and -20.1-68.9 ng/mL (rivaroxaban)]. CONCLUSION: Overall, the anti-Xa assays not supplemented with antithrombin and the HPLC-UV method proved to be suitable for apixaban and rivaroxaban quantification.

Metastatic Bilateral Strumal Carcinoid: A Case Report and Review of the Literature.

Primary ovarian carcinoids are very rare tumors that belong to the germ cell family of ovarian malignancies. They account for less than 1% of all carcinoid tumors and for less than 0.1% of all ovarian neoplasms. Recurrences are even rarer, with only few cases reported in the literature. Strumal carcinoid has recently been recognized as an extremely rare distinct entity. We report on a patient with bilateral mature cystic teratoma with millimetric foci of ovarian strumal carcinoid who developed lymph node para aortic metastasis after 30 years from primary diagnosis. Our case is thus far the second report of a metastatic strumal carcinoid and the first one in which strumal carcinoid occurred bilaterally and was also metastatic.

PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid.

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8-GLIS1 or PAX8-GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8-GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1-2 of PAX8 and exons 3-11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8-GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8-GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8-GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8-GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.

RESTORING KNEE EXTENSOR STRENGTH AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A CLINICAL COMMENTARY.

One of the main priorities of rehabilitation after anterior cruciate ligament reconstruction (ACLR) surgery is the restoration of knee extensor muscle strength. Residual deficits in knee extensor muscle size and strength after injury are linked to poor biomechanics, reduced knee function, increased knee osteoarthritis risk, as well as heightened risk of re-injury upon return to sport. Most studies indicate that knee extensor muscle strength is typically not resolved prior to return to sport. This clinical commentary discusses strategies to optimize and accelerate the recovery of knee extensor strength post-surgery, with the purpose to support the clinician with evidence-based strategies to implement into clinical practice. Principally, two strategies exist to normalize quadriceps strength after surgery, 1) limiting strength loss after injury and surgery and 2) maximizing and accelerating the recovery of strength after surgery. Optimal preparation for surgery and a focused attempt to resolve arthrogenic muscle inhibition are essential in the pre and post-operative period prior to the inclusion of a periodized strength training program. Often voluntary strengthening alone is insufficient to fully restore knee extensor muscle strength and the use of electrical stimulation and where necessary the use of blood flow restriction training with low loads can support strength recovery, particularly in patients who are significantly load compromised and experience pain during exercise. Resistance training should employ all contraction modes, utilize open and closed kinetic chain exercise of both limbs, and progress from isolated to functional strength training, as part of a periodized approach to restoring neuromuscular function. Furthermore, thinking beyond the knee musculature and correcting core and hip dysfunction is also important to ensure an optimal knee extension strengthening program. The purpose of this clinical commentary is to provide a series of evidenced based strategies which can be implemented by clinicians responsible for the rehabilitation of patients after ACLR. LEVEL OF EVIDENCE: 5.

Ultrasound-guided fine needle aspiration cytology in the diagnosis of hepatic and pancreatic perivascular epithelioid cell tumors: A case series.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that can affect any part of the body. They can be sporadic or arise in the setting of tuberous sclerosis (TSC). In this article, we report a series of three hepatic and two pancreatic PEComas diagnosed preoperatively with ultrasound-guided fine needle aspiration (FNA). All patients were female (age range 28-70), had no personal history of TSC and presented with a single, localized painless mass. Rapid on-site evaluation (ROSE) of cytologic samples was performed for all cases to evaluate for cellular content and adequacy of specimens. Direct smears and cell block preparations revealed a proliferation of medium to large polygonal epithelioid cells, with abundant eosinophilic and vacuolated cytoplasm, arranged in sheets and nests. On immunohistochemistry (IHC), neoplastic cells showed co-expression of melanocytic and smooth muscle markers and a diagnosis of PEComa was rendered. PEComas of the pancreas and liver are rare neoplasms, but should always be considered when examining "clear cell" neoplasms, especially in young female patients. If good quality cytologic samples are obtained by FNA, a correct diagnosis can be achieved with the help of IHC. This is of particular importance in order to plan adequate surgical strategy and to avoid overtreatment.

Nipple-Sparing Mastectomy: Reliability of sub-areolar sampling and frozen section in predicting occult nipple involvement in breast cancer patients.

INTRODUCTION: The oncological safety of nipple-areolar complex (NAC) preservation is a concern in the mastectomies performed for cancer indication. The detection of tumor cells during the intraoperative frozen section examination (IE) of sub-areolar/nipple tissue (SAT) leads to the removal of NAC, but frequently the final histology of the nipple is negative for malignancy. This study aims to evaluate the accuracy of SAT examination in predicting occult NAC involvement in case of Nipple-Sparing Mastectomy (NSM). METHODS: The study includes 76 NSM. We evaluated the concordance between histopathologic features of frozen and paraffin-embedded SAT sections. Moreover, we examined the "true margin" (TM), defined as the measurement of the distance between the tumor margin and the edge of the SAT. A margin >1 mm was considered negative. RESULTS: In 26/76 cases the IE of the SAT was positive. At the final histology, the NAC was negative in 57.7% of cases. The concordance between frozen and paraffin section examination of the SAT was 92.1%. The three false-positives were low-grade DCIS at the IE, and negative or DIN1a on permanent section. A negative TM seems to predict for a negative NAC (6/6). CONCLUSIONS: The detection of a low-grade DCIS at the IE of the SAT may not be confirmed at the permanent section examination; we recommend caution in removing the NAC in these cases. The evaluation of the TM may improve the accuracy of SAT analysis in predicting occult NAC involvement; in our series, a TM wider than 1 mm correlates with a negative NAC.