Weak Positivity Research Articles

Expression of epithelial–mesenchymal transition markers in squamous cell carcinoma of the uterine cervix: A cross-sectional study

Background: Cervical cancer is the fourth most common cancer in women worldwide. Epithelial– mesenchymal transition (EMT) is a phenomenon related to carcinogenesis, which is characterized by morphological changes from neoplastic epithelial cells to mesenchymal cells, resulting in increased motility and invasiveness of neoplastic cells. To observe the expression of three EMT markers (cytokeratin 19 [CK1]), vimentin, and Ras homolog gene family member C [RhoC]) in individuals with a normal cervix, patients with high-grade squamous intraepithelial lesion (HSIL), and patients with squamous cell carcinoma (SCC) and determine the association with the histological grade and clinical/radiological stage of cervical cancer. Methods: Seventy participants were included in the study: 10 individuals with a normal cervix, 30 patients with HSIL, and 30 patients with newly diagnosed SCC. Immunohistochemistry for CK19, vimentin, and RhoC was performed in all groups. The association of the expressions of the three markers between the groups was analyzed. P values of < 0.005 were considered statistically significant. Results: The mean age of the normal cervix, HSIL, and SCC groups was 46.2 ± 16.12, 49.10 ± 10.13, and 56.27 ± 9.29 years, respectively. CK19 showed a weak basal cell positivity in 80% of the individuals with a normal cervix. Meanwhile, 93.3% and 100% of the patients with HSIL and SCC, respectively, were positive for CK19; the association of the expressions between the groups was insignificant. Vimentin was negative in the normal cervix group and positive in the HSIL (33.3%) and SCC (73.3%) groups; the association of the expressions between the groups was significant. RhoC was positive in the normal cervix, HSIL, and SCC groups (10%, 20%, and 83.33%, respectively), and the association of the expressions between them was significant. There was no significant association found between the expression of vimentin or RhoC and the histopathological grade or FIGO stage. Conclusion: An increased expression of CK19 in patients with HSIL and SCC of the cervix highlights the role of basal cells in cervical carcinogenesis. The expression of vimentin and RhoC in individuals with a normal cervix and patients with HSIL and SCC indicates EMT.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Inhibin Alpha Expression in Human Tumors: A Tissue Microarray Study on 12,212 Tumors.

As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. In summary, these data support the use of INHA antibodies for detecting sex cord stromal tumors, granular cell tumors, and adrenocortical neoplasms. Since INHA can also be found in other tumor entities, INHA immunohistochemistry should only be considered as a part of any panel for the distinction of tumor entities.

DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR: A RARE CAUSE OF MALIGNANT PLEURAL EFFUSION

DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR: A RARE CAUSE OF MALIGNANT PLEURAL EFFUSION

Diagnostic Value of Nestin Expression in Adult Gliomas.

Introduction. Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies reported that the expression was associated with poor prognosis in brain tumors, but the results were inconclusive. In this study, we evaluated usefulness of nestin expression as a prognostic biomarker in consideration of IDH mutation and the World Health Organization (WHO) classification fifth edition. Methods. To investigate nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We analyzed the clinical characteristics and survival outcomes according to nestin expression and examined whether nestin expression alone affects the prognosis, independent of IDH mutation. Results. Sixty patients (65.2%) were nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with pathologic diagnosis and IDH mutation. The patients with high-grade gliomas showed a higher frequency and stronger intensity of nestin expression than those with low-grade gliomas (P < .001). The majority (93.6%) of gliomas with IDH mutation showed no expression or weak positivity. Multivariate Cox proportional hazard regression analysis for overall survival demonstrated that nestin expression (weak, hazard ratio [HR] 5.39, P = .036; strong, HR 8.43, P = .007) was an independent prognostic factor. Moreover, patients with nestin-expressing glioma showed shorter survival (P < .001). Conclusions. Nestin seems to be strongly expressed in the vast majority of glioblastomas, IDH-wildtype and rarely in IDH-mutant gliomas. Clear correlation between nestin expression and pathologic diagnosis makes an accurate patient diagnosis. Expression and intensity of nestin were significantly correlated with worse survival.

Hypothesis: HEG1 and claudin-4 staining will allow a diagnosis of epithelioid and biphasic mesothelioma versusnon-small-cell lung carcinoma with only two stainsin most cases.

Separation of mesothelioma from metastatic carcinoma requires immunohistochemical support, with small batteries of stains recommended as a starting-point, but these numbers commonly expand to 10, 12 or more stains, a process that is not only expensive but frequently generates anomalous or confounding results, leading to even more stains. Here we review data on HEG1 clone SKM9-2, a new (now commercially available) mesothelioma marker and claudin-4, a broad-spectrum carcinoma marker, to ask whether these two stains are sufficient, by themselves, to separate mesotheliomas from non-small-cell lung (NSCLC) as well as other carcinomas. Data for HEG1, derived from four laboratories, showed membrane staining in 393 of 434 (91%) epithelioid/biphasic mesotheliomas and one of 360 (0.3%) NSCLC (sensitivity 91%, specificity 99.7%). Reports from seven laboratories evaluating claudin-4 in NSCLC showed positivity in 469 of 502 (93%) carcinomas and weak positivity in five of 463 (1.0%) epithelioid/biphasic mesotheliomas (sensitivity 93%, specificity 98.9%). Comparable results were found with carcinomas from other sites, except for serous and thyroid carcinomas, some of which react with HEG1 but are also positive for claudin-4. For sarcomatoid mesotheliomas, HEG1 sensitivity is modest and staining sometimes difficult to interpret. We hypothesise that the combination of HEG1 and claudin-4 immunostaining will potentially allow the separation of epithelioid/biphasic mesotheliomas from NSCLC carcinomas with high accuracy using only two immunostains in most cases. This combination will probably also work for carcinomas from most other sites, but more reports on HEG1 SKM9-2 staining of carcinomas other than NSCLC are needed. This approach would greatly simplify the diagnosis of mesothelioma.

Villin expression in human tumours: a tissue microarray study on 14,398 tumours

Background Villin is a protein of the brush border of epithelial cells which is used as an immunohistochemical marker for colorectal and gastrointestinal neoplasms. However, other tumor entities can also express villin. Methods To comprehensively determine villin expression, tissue microarrays containing 14,398 samples from 118 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. Results Villin was found in 54 of 118 tumor categories, including 36 tumor categories with strong staining. Villin expression was frequent in colorectal, upper gastrointestinal tract, pancreatobiliary, and renal tumors as well as in mucinous ovarian cancers, yolk sac tumors and in neuroendocrine neoplasms. Reduced villin expression was linked to advanced pT stage, lymph vessel invasion and microsatellite instability (p≤0.0006) in colorectal adenocarcinoma. In summary, our data demonstrate that villin expression is most common in gastrointestinal, pancreatobiliary, and neuroendocrine neoplasms, yolk sac tumors and mucinous ovarian cancers. Conclusion Our data support a high utility of villin immunohistochemistry for the identification of tumors with gastrointestinal, pancreatobiliary, and yolk sac tumor origin. However, considering that at least a weak villin positivity in some tumor cells occurred in 54 different tumor categories, villin immunohistochemistry should be applied as a part of a marker panel rather than as a stand-alone marker.

Diagnostic significance of combined immunohistochemical panel of p63, High Molecular Weight Cytokeratin (34betaE12) and α‑Methyl Acyl Co A Racemase (AMACR) in resolving suspicious foci in prostatic lesions

Background: The assessment of small foci of atypical glands in prostatic needle biopsy specimens is a key diagnostic challenge in routine histopathology for pathologists. Due to the presence of mimickers of prostate carcinoma, at times making a definitive diagnosis becomes difficult. The use of immunomarkers like α‑Methyl Acyl Co A Racemase (AMACR), p63 and High Molecular Weight Cytokeratin (HMWCK/34betaE12) has made it easier for us to reach the diagnosis in such cases. Material and methods: All the cases which were received in the Department of Pathology, JNMCH, AMU from January 2015 to December 2018 were categorized into four histomorphologic groups on the basis of histopathology, and immunohistochemistry was applied on all the cases which were rendered ‘suspicious’ on histomorphology. Result: One hundred twenty-one prostatic specimens were received. Out of which, 13 biopsies were found to be inadequate for analysis and hence were not included in the study. Out of the rest 108 cases, (1) 52 were benign, (2) 19 were premalignant, (3) 25 were carcinoma and (4) 12 were signed as ‘suspicious’ on histopathology. These 12 suspicious cases were true cut needle biopsies which were considered appropriate for applying immunomarkers along with control cases. Out of 12 suspicious cases, 8 cases (66.7%) were negative and 3 cases (25%) were weakly positive for p63, 1 case showed moderate immunostaining. HMWCK was completely negative in 7 cases (58.33%), 3 cases (25%) showed weak positivity, 1 case showed moderate and 1 case showed strong positivity. While 5 cases (41.67%) were negative and 7 cases (58.33%) were positive for AMACR mostly showing moderate to strong positivity Conclusion: The application of immunomarkers helped us to reach a definite diagnosis in 10 out of 12 cases, which were otherwise difficult to classify. Judicious use of immunomarkers can help in differentiating mimickers of prostate carcinoma from true cancer cases and assist in reaching a definitive diagnosis.

Secretory carcinoma of breast with EGFR and weak ER positivity: A case report with discussion of distinguishing features

Secretory breast carcinoma (SBC) is a rare histologic type of indolent carcinoma breast, accounting for &amp;#60;0.5% of all breast cancers. It is characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. A 46-year-old woman presenting with palpable breast lump, was diagnosed as Secretory carcinoma following imaging and preoperative core-needle biopsy. Patient underwent neoadjuvant chemotherapy, followed by breast conserving surgery. The diagnosis was further confirmed on histopathology and Immunohistochemistry (IHC) with weak ER positive and EGFR positive tumour showing no expression of PR, Her2neu and CK5/6. Secretory carcinoma is a rare and special type of invasive breast carcinoma, with a wide age range and good prognosis. Inclusion of both basal markers (CK5/6,EGFR) on IHC and cytogenetic analysis are crucial for confirmation of SBC.

Lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma

Lymphoid hyperplasia is a type of tumor-like hyperplasia of lymphoid tissue. There have been few reports on lymphoid hyperplasia of the gallbladder. Here, we report a case of lymphoid hyperplasia with a polyp form of the gallbladder macroscopically mimicking carcinoma. Liver dysfunction was diagnosed in a 75-year-old woman who presented with a gallbladder mass measuring 20mm during an annual health checkup. Antibody tests for infectious diseases were positive for anti-HBs and anti-HBc antibodies. Accordingly, a laparoscopic cholecystectomy was performed. Macroscopically, the mass was a papillary/sessile tumor (29 × 25mm) located in the fundus of the gallbladder. Histologically, the tumor was accompanied by an erosion on a portion of the surface layer, while the remaining epithelium showed regenerative changes and mild hyperplasia. No atypia was observed in the constituent epithelium. Hyperplasia of the polarized lymphoid follicles was observed in the interstitium, and tingible body macrophages were scattered in the germinal center. Immuno-histologically, the germinal center showed CD20 positivity, weak CD10 positivity, Bcl-2 negativity, and a high Ki-67 index (MIB-1). These findings suggested that the proliferating lymphoid follicles were reactive rather than neoplastic. Therefore, we diagnosed the patient with lymphoid hyperplasia of the gallbladder and chronic cholecystitis.

A STUDY OF ORAL PREMALIGNANT AND MALIGNANT LESIONS WITH IMMNUNOEXPRESSION OF P53 AND BCL2.

CONTEXT- Histopathological examination of oral premaligant and malignant lesions, presenting the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its denition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Also immunoexpression of genes p53 and bcl2 attributed in pathogenesis of development of oral cancer. AIMS- Histopathological analysis of oral premalignant and malignant lesions and immunoexpression of Bcl 2 and p53 in these lesions. MATERIAL AND METHODS- This study was done in department of pathology, GSVM medical college, Kanpur. This was prospective study done from 2019-2021. A total of 200 cases were studied. Specimen received were xed in 10% formalin, processed and sections of 3-4 micron were prepared, stained with H and E. Histopathological examination was done. Anti p53, anti bcl2 antibody was used. Staining and evaluation of immunohistochemistry was done using Ab-5 (clone DO-7) ready to use as monoclonal primary antibody. RESULTS- th Maximum number of cases [24%] were in their 4th and 5 decades of life. Males predominated over females with male:female ratio of 3:1. In present study the most common site of oral mucosal lesions was buccal mucosa which accounted for 42% of total cases. . 88% cases had history of tobacco use, this data strongly suggest close association between tobacco and oral cancer. Most of the pre-neoplastic and neoplastic lesions of oral cavity &amp; oropharynx occur after 20-30 years of exposure to tobacco (37%), followed by 27% each after 0-20 years and 30-40 years of exposure. Gutkha chewing (tobacco) was the commonest observed in almost 50% cases. 69.5%belong to rural areas whereas only 30.5% cases were belong to urban areas. . Among premalignant cases, majority were of leukoplakia (30%) cases.Majority of the malignant cases were well differentiated squamous cell carcinoma. [23%]. Expression of p53 was found in 772.8% of the pre-malignant cases and 90.7% of the malignant lesions of the oral cavity. . It was found that 54.34% of premalignant lesions and 66.6% of malignant lesions showed strong p53 positivity. Most of the premalignant lesion showed mild positivity [50%]. 35% cases showed moderate positivity while none of the premalignant cases showed strong positivity. 52% cases of malignant lesions showed weak positivity. 45% cases showed moderate positivity and 13% had strong positivity. Intensity of staining increases with increasing grade of dysplasia and cancer. CONCLUSION- Pro apoptotic and anti apoptotic genes like p53 and bcl2 play an important role in early pathogenesis of oral cancer and their development from premalignant to malignant lesions. However, they are not the only genes involved as their tumorigenesis seemsmultifactorial.Targettedstudy towards thesegenes canstillbringfutureprospectsofgenetherapy tolight.

The Possible Protective Effect of Boric Acid in an Alkaline-Induced Corneal Neovascularization Rat Model.

It is known that boric acid (BA) exerts it antioxidant and anti-inflammatory effects by activating the activating transcription factor 4 (ATF4) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. This pathway has been reported to control antioxidant status in the eye. The aim of this study was to investigate the possible preventive effects of boric acid administration on oxidative damage and corneal neovascularization (CNV). Sixteen adult female Wistar albino rats were divided into two groups: (I) control (n = 8); the CNV model was applied to the right eye of the rats, and the left eyes were used as healthy controls. (II) CNV + BA (n = 8): After the CNV model was applied to the right eyes, a single subconjunctival dose (0.05mL) of 0,018g/mL BA was injected into the right and left eyes of the rats. Biochemical, histopathological, and immunohistochemical analyses were performed. Moderate VEGF positivity was observed in the vessels of the CNV group, a decrease in vessel proliferation, and weak VEGF positivity in the CNV + BA group. The TAS level in the CNV + BA group was significantly higher than that in the other groups. The TOS level was significantly higher in all groups than it is in the control group. The OSI value was increased in all groups when compared to the control group, but only the CNV and BA groups were statistically significant. BA not only reduced alkaline-induced corneal damage histologically but also showed a protective effect on oxidative stress biochemically.

Chondrosarcoma with Target-Like Chondrocytes: Update on Molecular Profiling and Specific Morphological Features

This is the first histological and molecular analysis of two chondrosarcomas with target-like chondrocytes that were compared with a group of conventional chondrosarcomas and enchondromas. The unique histological feature of target-like chondrocytes is the presence of unusual hypertrophic eosinophilic APAS-positive perichondrocytic rings (baskets). In the sections stained with Safranin O/Fast green, the outer part of the ring was blue and the material in the lacunar space stained orange, similarly to intercellular regions. Immunohistoche­mical examination showed strong positivity for vimentin, factor XIIIa, cyclin D1, osteonectin, B-cell lymphoma 2 apoptosis regulator (Bcl-2), p53 and p16. The S-100 protein was positive in 25 % of neoplastic cells. Antibodies against GFAP, D2-40 (podoplanin), CD99, CKAE1.3 and CD10 exhibited weak focal positivity. Pericellular rings/baskets contained type VI collagen in their peripheral part, in contrast to the type II collagen in intercellular interterritorial spaces. Ultra­structural examination revealed that pericellular rings contained an intralacunar component composed of microfibrils with abundant admixture of aggregates of dense amorphous non-fibrillar material. The outer extralacunar zone was made up of a layer of condensed thin collagen fibrils with admixture of non-fibrillar dense material. NGS sequencing identified a fusion transcript involving fibronectin 1 (FN1) and fibroblast growth factor receptor 2 (FGFR2) at the RNA level. At the DNA level, no significant va­riant was revealed except for the presumably germ­line variant in the SPTA1 gene. Erratum to this article was published in: Folia Biologica, 2022, 68, (5-6): 211–211. https://doi.org/10.14712/fb2022068050211

A case of repeated focal motor seizures as expression of an inflammatory cerebral process with suspected dysimmune etiology.

Autoimmune encephalitis (AE) is a condition of severe brain inflammation with a complex differential diagnosis. The identification of a specific neuronal antibody (NA) is not mandatory to diagnose AE. Moreover, even when a NA is detected, the clinical picture can be inconsequential (i.e., GAD-65) and not disease-specific (i.e., LGI1). Peculiar clinical manifestations and specific alterations of conventional tests as cerebral spinal fluid (CSF) and magnetic resonance imaging (MRI) can be sufficient to confirm the diagnostic suspicion of AE. New-onset seizures may be the first manifestation of AE and require immediate treatment. We report the case of a 19-year-old woman with sudden onset of focal motor seizures with unimpaired awareness, resistant to different intravenous antiseizure medications (ASMs). Ancillary tests (MRI, CSF analysis and electroencephalogram) were pathological and compatible with an autoimmune disorder of the brain. A weak positivity of GluR-3 antibody was detected in low serum dilution along with very high levels of angiotensin-converting enzyme in serum. After administration of high-dose corticosteroids, electro-clinical and neuroradiological pictures progressively normalized. This case report suggests that, even without a definite NA positivity, an inflammatory brain disorder of suspected autoimmune etiology should be considered based on clinical assessment and suggestive ancillary tests.

Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours.

Angiotensin-converting enzyme 2 (ACE2) is a regulator in the renin-angiotensin system. ACE2 expression was analysed immunohistochemically in 15,306 samples from 119 tumour types and in 608 samples of 76 normal tissue types. In normal tissue, ACE2 was most abundant in testis and corpus luteum, kidney, small intestine and capillaries of selected organs. At least an occasional weak ACE2 positivity of tumour cells was seen in 83 of 119 (70%) tumour types. ACE2 tumour cell positivity was particularly frequent in papillary (94%) and clear cell (86%) renal cell carcinoma, colorectal adenocarcinoma (81%), mucinous ovarian cancer (61%), cholangiocarcinoma (58%), hepatocellular carcinoma (56%), and in adenocarcinomas of the stomach (47%), pancreas (42%), and the lung (35%). ACE2-positive capillaries were found in 409/12,644 (3%) of analysable tumours, most frequently in tumours with endocrine/neuroendocrine activity. Presence of ACE2-positive capillaries was linked to low stage in papillary thyroid cancer and low grade in neuroendocrine neoplasms. In conclusion, ACE2 expression can occur both in tumour cells and tumour-associated capillaries in a broad variety of different tumour types at highly variable frequencies.

Which Level of Emicizumab Is Necessary for a Good Hemostasis?

IntroductionEmicizumab is a recombinant, humanized, bispecific antibody restoring the function of missing activated factor VIII (FVIII) by bridging activated FIX (FIXa) and zymogen factor X (FX), medicating the activation of FX. Emicizumab is approved in several countries, at the doses of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks, for the prophylaxis of bleeding episodes in patients with hemophilia A with and without inhibitors. The drug has shown a good efficacy either during registration studies as well as in real-world experiences and was well tolerated without significant side effects. The development of neutralizing anti-emicizumab antibodies has been reported in very few cases which frequently required the switch to other products due to inefficacy of the prophylaxis. Patients maintaining a plasma concentration range of the drug within 30-80 ug/ml did not show significant bleeds. However, real life experiences bring the need of personalization of the drug dose. A recent case series presented at ISTH 2021 from Malaysian authors evaluated the efficacy of a dose of emicizumab between 1.7 and 1.9 mg/kg every 4 weeks, showing that even at a lower dose than that approved could be effective for the prevention of bleeding events. Here we report the case of an adult patient with moderate hemophilia A with inhibitor who developed an anti-emicizumab antibody which reduced the concentration of the drug by 50%. Despite that the patient did not report bleeding events in a follow-up period of 18 weeks. Treatment with emicizumab requires further evaluation to understand the best dose for the prevention of bleeding.Case reportA 74 years old patient with moderate hemophilia A (FVIII 1-3%) followed at our Center had history of high-titer inhibitor (maximum titer 20 BU). The patient was treated on-demand with plasma-derived FVIII concentrates, when, in Jul 2000, he developed a neutralizing anti-FVIII antibody requiring treatment with activated prothrombin complex concentrates (Feiba). In Nov 2020 the patient was hospitalized for traumatic brain hemorrhage treated with plasma-derived FVIII (inhibitor titer < 5 BU) and subsequently, for the recurrence of inhibitor, with activated prothrombin complex concentrates. In Feb 2021 the patient started prophylaxis with emicizumab at the initial dose of 3 mg/kg once weekly (loading dose), followed by a maintenance dose of 1.5 mg/kg. The patient underwent periodic blood withdrawal for monitoring drug plasma concentration. In Apr 2021 (week 10) drug concentration showed a slight decrease from initial levels, from 39.1 ug/ml (week 5) to 28.3 (week 10) and a weak positivity for an anti-emicizumab antibody was detected. At the following test (week 15) positivity for the anti-emicizumab antibody was confirmed, witnessed by the consistent reduction in drug plasma concentration up to 20.9 ug/ml. During the following weeks, until week 22, drug plasma concentrations were stable (range 17.0-19.4 ug/ml) and positivity for anti-emicizumab antibody remained, as shown in the table. The results of partial Thromboplastin Time (PTT) were consistent with the drug plasma concentrations during the observation period, in which the patient did not developed any bleeding event.ConclusionThis case report may corroborate the hypothesis of the efficacy of a reduced dose of emicizumab in patients with hemophilia A. Close laboratory monitoring in patients in prophylaxis with emicizumab is warranted for the evaluation of drug plasma concentration and the prompt detection of anti-drug antibodies, particularly if patient show a reduced therapeutic efficacy. However, in the absence of bleeding events, positivity for anti-emicizumab antibodies should not bring to sudden drug discontinuation. Indeed, in the view of the above, a lower drug plasma concentration than standard might be effective in the prevention of bleeding.1. Tang ASO et al. July 2021. Efficacy of Reduced-dose Emicizumab in Haemophilia A with Inhibitors: Real World Experience in East Malaysia. ISTH 2021. [Display omitted] DisclosuresPeyvandi: Takeda: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

A Challenging and Rare Case of Metastatic Follicular Dendritic Cell Sarcoma Originating from a Tonsil

Abstract Introduction/Objective Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor of follicular dendritic cells. Most cases of FDCS are described in lymph nodes, but it can involve extra-nodal locations such as the tonsil. Methods/Case Report We report a case of a 55-year-old male with a 6-month history of a slow growing left neck mass. The patient had a poorly differentiated carcinoma of the left tonsil diagnosed based on morphologic features eight years ago, followed by chemoradiation, and subsequent left tonsillectomy without tumor identified. Imaging reported a 4.0 cm mass in the left neck level III lymph node location. Biopsy of the mass revealed a spindle cell neoplasm. It was difficult to reach a definitive diagnosis despite an extensive work-up. Review of the previous left tonsil biopsy showed a pleomorphic epithelioid cell proliferation. On the radical resection specimen of the left neck mass, a 4.5 cm, tan-gray, fleshy, necrotic mass was present. Microscopically, it demonstrated a neoplasm with spindle cell and epithelioid cell proliferation, with extensive necrosis. A wide panel of immunostains was performed; the tumor cells showed positivity for CD21, CD23, CD35, and focally weak positivity for cytokeratin OSCAR and Synaptophysin. Squamous cell markers were negative. These findings are consistent with FDCS. Further work-up on the original tonsil tumor displayed immunostaining profile of FDCS. This case was consulted with the National Institute of Health (NIH) for confirmation of the diagnosis. Results (if a Case Study enter NA) NA Conclusion Morphologically, FDCS can present with various histologic patterns, which can lead to diagnostic pitfalls, and common confusion with poorly differentiated carcinoma or soft tissue tumors, especially in needle biopsies. Generally, patients present with a prolonged clinical course, with a 50% and 25% chance of recurrence and metastasis respectively, hence the awareness and accurate diagnosis of this entity is important in biopsies of lymph nodes or of extranodal locations such as a tonsil.

Which Clinicopathologic Parameters Suggest Primary Resistance to Palbociclib in Combination With Letrozole as the First-Line Treatment for Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer?

In this study, we evaluated clinical parameters to predict the primary resistance of palbociclib in combination with endocrine therapy as the first-line treatment in patients with hormone receptor (HR)+, human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer (MBC). We performed a data analysis of patients diagnosed with HR+, HER2-MBC who received palbociclib plus letrozole as the first-line treatment in the metastatic setting from the clinical data warehouse in Samsung Medical Center. In this study, 305 patients were included in the final data analysis. The median follow-up duration was 31 months, and we observed 123 cases of disease progression. The median progression-free survival (PFS) was 28.7 months, and 38 patients (12.5%) had less than a 6-month PFS. The multivariate analysis suggested that primary resistance to adjuvant endocrine therapy (ET) (hazard ratio: 1.91), presence of liver metastasis (hazard ratio: 2.17), initial elevation of serum CA-15-3 (hazard ratio: 1.99), weak positivity of estrogen receptor (ER) (hazard ratio: 2.28), Ki-67 3+ or 4+ (hazard ratios: 2.58 and 10.28), and presence of mutation (hazard ratio: 9.59) were associated with a short PFS duration. A further prediction model was developed with data from 256 patients and 33 cases of disease progression in 6 months. This model included five factors—primary resistance to adjuvant ET (odds ratio, OR: 1.14), liver metastasis (OR: 1.56), initial CA-15-3 elevation (OR: 1.51), weak ER expression (OR: 2.22), and BRCA2 mutation (OR: 2.85)—and the area under the receiver operating characteristic curve was 0.842 (95% CI: 0.775, 0.909; p < 0.001). Finally, we divided them into four risk groups according to the prediction model with the five risk factors. These four groups had different PFS (p < 0.001) and primary resistance of palbociclib with letrozole [OR of group 2 vs. group 1 (ref): 2.18 (p = 0.002), OR of group 3: 3.91 (p < 0.001), and OR of group 4: 4.25 (p < 0.001)]. We developed a prediction model of primary resistance to palbociclib with letrozole as the first-line treatment for HR+, HER2-MBC. Our prediction model might be helpful for considering the first-line treatment strategies. Further well-designed clinical trials would be warranted to validate our prediction model.

Association of extended myositis panel results, clinical features, and diagnoses: a single-center retrospective observational study

Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) are a feature of the idiopathic inflammatory myopathies (IIM), but are also seen in other rheumatic diseases, and in individuals with no clinical symptoms. The aim of this study was to assess the clinical utility of MSA and MAA and in particular the clinical relevance of weakly positive results. We included all patients at our institution who had at least one positive result on the Immunoblot EUROLINE myositis panel over a 6-year period (2015–2020). Associations with clinical features and final diagnosis were evaluated. Eighty-seven of 225 (39%) myositis panel tests met the inclusion criteria. There were 52 strong positives and 35 weak positives for one or more MSA/MAAs. Among the strong positive group, 15% (8/52) were diagnosed with IIM, 34.6% (18/52) with interstitial lung disease, 7.7% (4/52) with anti-synthetase syndrome, 25% (13/52) with connective tissue disease, and others accounted for 25% (13/52). In weak-positive cases, only 14% (5/35) had connective tissue disease and none had IIM. 60% (21/35) of weak-positive cases were not associated with a specific rheumatic disease. A significant number of positive myositis panel results, particularly weak positives, are not associated with IIM or CTD.

Pancreatic hepatoid carcinoma: A case report and literature review

Hepatoid carcinomas (HCs) are a group of heterogeneous tumors that are similar to hepatocellular carcinoma (HCC). Pancreatic hepatoid carcinoma (PHC) is a very rare disease. The present study presents the case of a 63‑year‑old male patient with PHC with synchronous liver, spleen and stomach metastasis, in an aim to enhance our understanding of this disease. A 63‑year‑old male presented with abdominal distension for 3 months and slightly developed asthenia and anorexia. Laboratory tests of serum tumor markers revealed the alpha fetoprotein level was markedly elevated (&gt;10,00.0 ng/ml). The radiological findings of computed tomography, magnetic resonance imaging, diffusion‑weighted imaging and magnetic resonance cholangiopancreatography revealed a malignant tumor in the tail of the pancreas with synchronous liver, spleen, stomach and retroperitoneal lymph node metastasis. A post‑operative immunohistochemical analysis revealed that the tumor cells in the tail of the pancreas exhibited positivity for glypican‑3; right liver positivity was also observed for CK‑18 and weak positivity for glypican‑3, suggestive of primary PHC. On the whole, PHC is very rare, and exhibits morphological features similar to those of HCC. Its diagnosis is mainly achieved via morphological analysis and immunohistochemical staining of the tissue specimens, since the clinical manifestation and laboratory test results are often unspecific.