Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017-2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

Validation of the Human Papillomavirus Impact Profile in Lebanese Women With Human Papillomavirus or Associated Lesions.

OBJECTIVES: Human papillomavirus (HPV) is responsible for a multitude of lesions with high psychosocial burden. The "HPV Impact Profile" (HIP) questionnaire is one of the first and most specific tools evaluating the emotional impact of HPV. This study aimed to translate this questionnaire into Arabic and to validate it, in a sample of Lebanese female patients. MATERIALS AND METHODS: The HIP questionnaire was translated to Arabic. It was then administered to 118 Lebanese women infected with HPV or screened for HPV-associated lesions, in parallel with the Hospital Anxiety and Depression Scale questionnaire. The psychometric properties of the questionnaire were studied in our sample population. RESULTS: The internal consistency of the HIP questionnaire was weak as Cronbach α coefficients of most of the domains were low. The study of the composite matrix resulted in the improvement of the internal consistency after the elimination of some items. Moreover, the "adapted domains" were created by reverse-scoring items with positive implications.The composite reliability and the average variance extracted of all the domains were analyzed. Analysis of discriminate validity through heterotrait-monotrait ratio of correlation ratio analyses of corresponding Hospital Anxiety and Depression Scale domains was also performed along with reliability analysis. There results were satisfying for the adapted domains. CONCLUSIONS: The adapted domains of the 27 items questionnaire with reverse scoring of 8 items presented with good psychometric properties, allowing their use in clinical trials and in clinical practice.

Does Social and Religious Background Matter? A Study of the Psychosocial Impact of Human Papillomavirus on Lebanese Women.

OBJECTIVE: The human papillomavirus (HPV) has been associated with an important psychosocial impact. This impact has been poorly evaluated in developing countries, mostly because of the lack of instruments to quantify it. The HIP questionnaire aims to measure HPV-associated affective burden. Our team has previously translated this questionnaire to Arabic and used it to assess the impact of HPV on Lebanese women. MATERIALS AND METHODS: While the HIP is a specific tool to evaluate the emotional impact of HPV, the Hospital Anxiety and Depression Scale questionnaire consists of 2 scales, anxiety and depression, and assess the psychological distress in nonpsychiatric patients. The HPV impact profile and Hospital Anxiety and Depression Scale questionnaires were administered to 118 Lebanese women with an HPV-related presentation, aiming to determine which aspect of these women's lives was mostly affected. The association with different sociodemographic factors was also assessed. RESULTS: Feelings of "concerns and worries" were mostly strongly felt in our population except for women with genital warts who were more concerned with the risk of transmission and the impact on their partners. All women had predominant feelings of anxiety.Religion was a statistically significant influencing factor and employment a protective factor. Muslim women demonstrated significant adverse affects on HPV impact profile domains that included: "sexual impact," "self-image," "interaction with doctors," and "health control/life impact." CONCLUSIONS: Different women perceive the diagnosis of HPV and HPV-related lesions differently. In this study, employment was found to play a protective role, but the biggest influencers were social and religious beliefs.

A case of pelvic actinomycosis affecting genital, urinary and digestive tracts: a rare misleading diagnosis.

Pelvic actinomycosis is an uncommon chronic invasive disease caused by a bacteria of the Actinomyces spp. Its diagnosis constitutes a clinical challenge and is usually reached in the postoperative period after resecting a pelvic mass that usually mimics advanced ovarian cancer. Although pelvic actinomyocosis involving the digestive and genital tract has been commonly described, very few reports have described cases involving both ovaries and requiring partial cystectomy for bladder involvement. Herein, we illustrate a case of pelvic actinomycosis with extensive involvement of multiple pelvic organs, misleading the surgeon into undergoing a complete clearance of the wrongfully thought adnexal malignancy.

Characteristics and Outcome in Non-Puerperal Uterine Inversion.

Chronic non-puerperal uterine inversion is rare and usually associated with uterine pathology with a diagnosis that is challenging. We present the case of a 47-year-old para 4 Caucasian woman with a history of polyfibromatous uterus who was admitted for severe vaginal bleeding for the past 48 hours associated with hemodynamical instability and was refusing any surgery. Pelvic MRI showed the uterus presenting an unusual appearance with a highly vascularized intracavitary leiomyoma protruding through the cervix. Upon deterioration of her status despite an optimal blood transfusion, resuscitation and anti-fibrinolytic treatment, she accepted total abdominal hysterectomy. The diagnosis of uterine inversion was made intraoperatively and confirmed on histopathologic examination. It revealed two side-by-side benign fundal leiomyomas which had collapsed the fundus and protruded partly from the cervix. Non-puerperal chronic inversion of the uterus is rare, and its diagnosis should be based on ultrasound, pelvic MRI and a high index of suspicion, allowing rapid diagnosis and treatment and thus decreasing patient morbidity and mortality.

Periductal stromal tumor of the breast in a young lady: A case report.

We present the case of a 30-year-old lady who underwent a core needle biopsy for a BIRADS 4 lesion of her left breast and was diagnosed as having a cellular fibroadenoma. The final diagnosis after excision returned to be a periductal stromal tumor (PST). An extremely rare entity, the PST is actually classified as a subtype of phyllodes tumor, with specific criteria that are only found upon histological examination of the specimen. Care should be taken when considering the diagnosis of fibroadenoma based only on clinical, radiological, and biopsy findings. Any nonclassical, clinical, or radiological findings should prompt a wide excision. Prognosis is generally good when clear margins are obtained and in the absence of malignant heterologous elements.

Radiology management of a 'breast unit' during COVID-19 pandemic: a single institution experience.

Aim: To describe the activity in the 'breast unit' at the department of radiology during the COVID-19 lockdown in a university hospital treating COVID-19 patients in a Middle-Eastern developing country. Materials: This was a retrospective study conducted from March 9 until 11 May 2020, in the breast unit at the department of radiology of a central university hospital in a Middle-Eastern developing country. Data were collected from 205 patients visiting the breast unit during the lockdown period and compared with the activity in the same period in the previous year. Results: Reduction of the breast unit activity was estimated at 73%. In addition, 153 mammograms, 205 ultrasounds, and 16 breast MRIs were done. Indications for mammogram were screening (41.5%), follow-up (22%), clinical symptoms (20%) and breast cancer surveillance (16.5%). MRI was performed mostly for preoperative surgical management. The rate of positive biopsies was 41%. All staff members and patients have accommodated to new adjustments. Conclusion: Activity in the breast unit dropped during the lockdown period. Staff should continue to seek their own and their patient's safety without diminishing the quality of healthcare.

Different TP53 mutants in p53 overexpressed epithelial ovarian carcinoma can be associated both with altered and unaltered glycolytic and apoptotic profiles.

BACKGROUND: p53 is a tumor suppressor and key regulator of glycolysis in cancer cells, however highly mutated in tumors. In ovarian cancer, studies concerning p53 mutations focus on the DNA binding domain since the majority of hotspot mutations affects this region. Yet, mutations in other regions such as the proline rich domain may also affect the protein's expression and activity. The aim of this study is to investigate the effect of various positions of mutations in TP53 gene on glycolysis, apoptosis and transcription of p53 target genes. METHODS: Mutations frequency and their effect on p53 expression were assessed by PCR-SSCP, sequencing and immunohistochemistry on 30 ovarian cancer biopsies. Six tumors were cultured, as well as SK-OV-3, OVCAR-3 and Igrov-1. SK-OV-3 cells were transfected with 2 TP53 mutants. p53 transcriptional activity was assayed by qPCR, apoptosis by flow cytometry and glycolysis by glucose and lactate measurements, with quantification of glycolytic enzymes expression. RESULTS: Our results showed a high frequency of the P72R mutant, associated with p53 overexpression in the ovarian biopsies. However, P72R mutant cells showed similar apoptosis and glycolysis as WT cells. DNA binding domain mutations decreased the transcriptional activity of the protein and increased glucose consumption and lactate production. CONCLUSION: Despite the overexpression of the P72R mutated protein in the biopsies, it showed a similar apoptotic activity and glucose regulation ability as WT p53. Knowing that p53 expression status is used for chemotherapeutic approaches and prognosis in ovarian cancer, the results obtained highlight the importance of locating TP53 mutations.

Loss of heterozygosity in tumor tissue in hormonal receptor genes is associated with poor prognostic criteria in breast cancer.

The estrogen receptors (ESRα and ß) and the androgen receptor (AR) mediate genomic and non-genomic effects on breast tumor growth and proliferation. We analyzed 101 breast cancer patients for allelic loss in microsatellites located in regulatory regions of the ESRs and AR genes in breast cancer tumors. The loss of heterozygosity (LOH) at these loci was found in 36.2% of tumor tissues (ductal carcinoma cases), for 19% of cases at the ESRα locus, for 16% at the ESRß locus, and for 10% at the AR locus. The LOH in at least one of the two ESR loci was correlated to poor prognosis criteria: ESR-negative status (P = 0.007), PR-negative status (P = 0.003), high Scarff-Bloom-Richardson (SBR) grade (P = 0.0007), high MIB-1 proliferation index (P = 0.02), and diminished apoptosis potential (TP53-positive status, P = 0.018). When AR was also considered, the LOH in at least one of the three loci was associated with ESR-negative status (P = 0.036), PR-negative status (P = 0.027), high SBR grade (P = 0.005), high mitotic index (P = 0.0002), TP53-positive status (P = 0.029), and proliferating index (high MIB-1, P = 0.03). Allelic loss was observed in 26% of normal tissue adjacent to tumor with LOH at the ESRα locus and in 7.1% of tumors with LOH at the ESRß locus. The LOH in tumor tissue in the regulatory regions of ESRα, ESRß, and AR genes has potentially synergistic effects on tumor proliferation, histological aggressiveness, down-regulation of ESRα and progesterone receptor (PR) genes, and is an early genetic alteration in cancer that is possibly involved in passage to estrogen independence.

OSNA (one-step nucleic acid amplification) sentinel lymph node intraoperative molecular analysis in breast cancer: a cost-benefit analysis.

The aim of the study was to analyze the medical and economic interest of OSNA molecular technique, compared to conventional postoperative histopathologic evaluation for sentinel lymph node exploration in breast cancer patients. This retrospective cost-benefit study was conducted in the French Universitary Hospital of Saint Etienne on patients who received sentinel lymph node exploration between July 1, 2007 and December 31, 2009. Lymph nodes were analyzed by conventional postoperative histological evaluation in group 1 (82 patients) and OSNA in group 2 (86 patients). Costs were analyzed in three different ways: surgery cost, hospitalization cost and histopathologic cost. Average operating time was slightly shorter for group 1 (histology) [71.9 vs. 76.8 min for group 2 (OSNA)]. Time and operating costs were not significantly different (p = 0.293). The average cost of pathological examination was significantly higher in group 2 (35.04 euros per node in group 1 vs. 291.84 euros per node in group 2 p < 10(-3)). The average length of hospital stay was significantly longer in group 1 (5.4 days in group 1 vs. 4.2 days in group 2, p = 0.0065). The total costs were not significantly different between both groups (3,774.6 euros in group 1 vs. 3,393.9 euros in group 2 p = 0.055). The sentinel lymph node analysis with OSNA technique does not lead to higher expenses. It also avoids another surgery for 20% of patients. A prospective multicentric medico-economic study made with a larger effective would probably confirm these results.

Implementation of molecular intra-operative assessment of sentinel lymph node in breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy is used as a staging procedure in early breast cancer, however, histology based intra-operative assessment of the SLN status has a low sensitivity. The one-step nucleic acid amplification (OSNA) method was developed to detect metastases by amplification of cytokeratin (CK) 19 mRNA. Experience with OSNA during a French multi-centric prospective study, as well as intra-operative clinical routine use, is reported. PATIENTS AND METHODS: For the clinical study 80 SLNs from 46 patients were assessed. During routine use, the central slice of the SLN from 197 patients was investigated by permanent histology and the remainder was assessed by OSNA. RESULTS: During the clinical study, OSNA detected 15/17 metastases, including all the macrometastases, reaching a 96.3% concordance rate, 88.2% sensitivity and 98.4% specificity. During routine use, both OSNA and histology detected 25 patients with metastasis. CONCLUSION: OSNA is an accurate tool for intra-operative assessment of SLN status and could reduce the need for second surgery.

Three-dimensional sonographic diagnosis of abdominal wall endometriosis: a useful tool?

OBJECTIVE: To report the usefulness of three-dimensional (3D) ultrasonography for the assessment of parietal endometriosis. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A 35-year-old woman with a noncyclic, painful abdominal nodule near a caesarean delivery scar. INTERVENTION(S): 3D ultrasonography and wide surgical resection with healthy margins. MAIN OUTCOME MEASURE(S): 3D ultrasonographic assessment of the endometriotic nodule. RESULT(S): We found that 3D ultrasonography offered a more specific description of parietal endometriosis with irregular and spiculated margins and depth infiltration as well as provided preoperative evaluation of volume measurements. CONCLUSION(S): Three-dimensional ultrasonography is a useful, noninvasive tool in extrapelvic endometriosis.

Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (<65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.

Atypical presentations of solitary fibrous tumors of the central nervous system: an analysis of unusual clinicopathological and outcome patterns in three new cases with a review of the literature.

Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms recognized less than a decade ago. Approximately 60 cases of SFT have been reported in the central nervous system. We describe three atypical SFTs of the CNS, two intracranial and one within the spine. One intracranial SFT arose from the sella turcica and expanded into the suprasellar areas. It relapsed twice during the 3 years following partial resection, and the MiB 1 labeling index steadily increased without obvious malignant transformation. The second SFT arose from the confluence of the sinuses, widely invaded the lateral sinus and adjacent bones, had a low MiB 1 index and has not recurred after 5 years. The intraspinal tumor occurred at T5-T7 in a patient with multiple café-au-lait spots, was predominantly myxoid and developed a second similar lesion at S3-S5 14 years later. The MiB 1 index was lower in the second tumor. Immunohistochemistry confirmed that all were SFTs. These atypical presentations gave us an opportunity to provide further information about the natural histological course of CNS SFTs.

Feasibility of the detection of the sentinel lymph node in peripheral non-small cell lung cancer with radio isotopic and blue dye techniques.

STUDY OBJECTIVES: The objective of this study was to evaluate the feasibility of the sentinel lymph node (SLN) biopsy in peripheral clinically stage I or II non-small cell lung cancer (NSCLC) using (99m)Tc colloid and a hand-held gamma detection probe, associated with a blue dye technique. DESIGN: Prospective study. SETTING: Royal Brompton Hospital, London, UK; and Hopital Nord, Saint Etienne, France. METHODS: After thoracotomy, a total of 2 mL patent blue dye mixed with 1,600 muCi (99m)Tc-albumin or (99m)Tc-colloid was injected into each quadrant of lung tissue immediately surrounding the tumor. Routine lymphadenectomy was carried out. The first lymph nodes to stain blue or radioactive, if any, were considered SLNs. RESULTS: Twenty-four patients were evaluated. We successfully identified 17 SLNs in 13 patients (detection rate, 54.2%). Mean time from injection to identification of SLNs was 18 min (range, 5 to 30 min). In nine cases, the SLN was blue and radioactive, in six cases only blue, and in two cases only radioactive. The pathologic status of the SLN reflected the pathologic status of other nodes of the routine lymphadenectomy except one case of false-negative SLN (14%). Four SLNs were in N2 stations (23.5%). CONCLUSIONS: The sentinel node mapping in NSCLC with blue dye and radioisotopic techniques is feasible, but the detection rate has to be improved. This technique is an accurate method of identifying the first node draining a tumor, although it is not yet sufficiently sensitive to have a role in reducing the extent of nodal dissection.

Desmoplastic infantile ganglioglioma: a rare tumor with an unusual presentation.

Desmoplastic infantile ganglioglioma (World Health Organization grade I) is a rare neoplasm. Despite their common large size and spectacular radiologic and histologic features, the prognosis after surgical resection is good. We present a new case of this tumor in a 14-month-old boy with a recent history of intracranial hypertension. Magnetic resonance imaging revealed a large tumor involving the left collateral trigone with dilatation of the lateral ventricles. Surgery revealed two separate solid tumors: one in the left falco-tentorial region and the other in the left rolandic area. Microscopic examination showed a proliferation of neoplastic astrocytes in reticulin-rich desmoplastic stroma associated with scattered ganglion cells. One year after surgery follow-up magnetic resonance imaging did not show tumor progression.