Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and ß-catenin in infiltrating breast carcinoma of no special type.

BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/ß-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and ß-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and ß-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis. MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and ß-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and ß-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered. RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant ß-catenin expression. High KIF18A and ß-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and ß-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low ß-catenin H score. CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating ß-catenin. Overexpression of KIF18A and aberrant expression of ß-catenin are considered proto-oncogenes of breast cancer development. KIF18A and ß-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.

Role of Serine arginine protein kinase 1 and Minichromosome maintenance protein 2 in predicting epithelial ovarian cancer response to treatment and prognosis.

BACKGROUND: Serine-Arginine (SR) proteins are a conserved family of proteins involved in RNA splicing and are reported to be over-expressed in multiple cancers. The aim of the study is evaluation of the expression of Serine arginine protein kinase 1 (SRPK1) and Minichromosome maintenance protein 2 (MCM2) in epithelial ovarian cancer (EOC) and their correlation with clinicopathological features, response to therapy, progression-free survival (PFS), and cancer-specific survival (CSS). METHODS: This study was carried out on surgical specimens of 65 patients diagnosed with EOC which were submitted to immunohistochemical staining by SRPK1 and MCM2 antibodies. RESULTS: About 89.2% of cases showed SRPK1 expression and its high expression was significantly associated with type II tumors and advanced stage. All cases showed nuclear immunoreaction for MCM2 with high expression in 49.2% of cases. There was a significant relationship between high values of SRPK1 H-score and percentage of MCM2. Postmenopause, type II pathology, advanced stage, absence of complete response to the treatment, resistance to platinum-based chemotherapy, and surgery done by a general surgeon were the factors affecting PFS. Response to treatment and platinum sensitivity were the most independent factors affecting patients' PFS. The factors associated with shorter CSS were suboptimal debulking, advanced stage, absence of complete response to the treatment, platinum resistance, and high SRPK1. High SRPK1 expression and platinum sensitivity were the independent factors affecting patients' CSS. CONCLUSIONS: SRPK1 is an unfavorable biomarker in EOC patients because of its association with aggressive histologic type, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, and worse survival. SRPK1 could promote the proliferation of EOC by up-regulation of MCM2.

Immunohistochemical Expression of Angiotensin-Converting Enzyme 2 in the Skin of Patients Affected by COVID-19.

BACKGROUND: After many recorded cases of acute pneumonia of unknown cause, the World Health Organization announced COVID-19 as the start of a new coronavirus disease pandemic in 2019. Angiotensin-converting enzyme-2 (ACE2) is reduced by a protease known as transmembrane serine type 2 in the host cell, which then activates the S protein of SARS-CoV-2 regulating coronavirus entry into the host cells. AIM: The aim of this study was to assess the immunohistochemical expression of ACE 2 in the skin of patients affected by COVID-19 with and without cutaneous manifestations and to correlate ACE2 expression with clinical and pathologic parameters. METHODS: Skin biopsies were obtained from skin lesions of 25 patients presenting with cutaneous manifestations and from the left forearm of 22 patients without cutaneous manifestations. The specimens were processed for evaluation of histopathologic changes and ACE2 immunohistochemical evaluation. RESULTS: Positive ACE2 expression was significantly higher in patients without cutaneous manifestations (96%) than those with cutaneous manifestations (72.7%). Positive ACE2 expression in the skin of affected patients was significantly associated with the presence of comorbidities, positive family history, high ABCD score, elevated lactate dehydrogenase, high D-dimer, rapid respiratory rate, and low oxygen saturation. CONCLUSIONS: The skin could be involved in COVID-19 infection in the form of inflammatory changes, such as pityriasis rosea-like lesions. Patients with COVID-19 who presented with cutaneous manifestations are usually less severe. The presence of ACE2 in the skin of patients with COVID-19 is an indicator of worse status. Patients with COVID-19 without skin manifestations showed higher positivity for ACE2, which may explain the severity of the cases.

Could α MSH-MIFT Axis and IDH2 be Considered Promising Predictors of Non-segmental Vitiligo Response to NB-UVB Phototherapy?

Background: The search for objective factors that help in predicting the response of vitiligo treatment is very important. Objective: We sought to evaluate the effect of NB-UVB phototherapy on both the alpha melanocyte stimulating hormone-microphthalmia-associated transcription factor (α-MSH-MIFT) axis, and isocitrate dehydrogenase 2 (IDH2) in non-segmental vitiligo (NSV). Methods: This prospective clinical trial included 50 NSV patients and 50 healthy control subjects. α-MSH tissue levels as well as MITF and IDH2 immunostaining were assessed in normal and vitiliginous skin biopsies before treatment and then in the repigmented areas following 24 NB-UVB phototherapy treatment sessions using ELISA technique and immunohistochemical study, respectively. Results: There was a significant negative correlation between baseline VASI scores and the tissue levels of α-MSH (p=0.006) and the expression of both MITF (p<0.00001) and IDH-2 (p= 0.001). The mean α-MSH tissue levels increased significantly after treatment (p<0.001). Tissue expression of both MTIF and IDH-2 was significantly upregulated following treatment (P-value <0.001). The percentage of improvement showed a significant positive correlation with the studied markers (p<0.00001). Conclusion: α-MSH- MIFT axis and the antioxidant protein IDH2 are promising objective markers of non-segmental vitiligo severity, and are suggested as predictors of vitiligo response to treatment.

The Prognostic Impact of Tumor Border Configuration, Tumor Budding and Tumor Stroma Ratio in Colorectal Carcinoma.

OBJECTIVE: Tumor border configuration, tumor budding and tumor stroma ratio are reliable histopathological parameters that play a central role in the invasion-metastasis cascade. This study aimed to investigate the prognostic impact of these parameters and a new combined score in colorectal cancer. MATERIAL AND METHOD: A cohort of 103 colorectal cancer surgical specimens was retrospectively evaluated for tumor border configuration, tumor budding and tumor stroma ratio using H&E sections. A combined risk score was then constructed to divide cases into low risk-tumors and high risk-tumors. RESULTS: Infiltrating tumor border, high tumor budding, low tumor stroma ratio and high combined risk score were associated with positive lymph node involvement, presence of metastasis, high tumor grade, lymphovascular invasion, poor overall survival and short recurrence-free survival. Infiltrating tumor border, high tumor budding and high combined risk score were associated with advanced T stage. High tumor budding, and low tumor stroma ratio were associated with perineural invasion. Infiltrating tumor border was associated with increased tumor size and conventional adenocarcinoma, high tumor budding and low tumor stroma ratio. Low tumor stroma ratio was associated with high tumor budding. On multivariate survival analysis, tumor stroma ratio was found to be an independent predictor for overall survival and recurrence-free survival. CONCLUSION: Tumor border configuration, tumor budding, tumor stroma ratio and the newly constructed combined risk score are potential predictors of outcome in colorectal cancer patients, suggesting that their incorporation in the routine histopathological evaluation could be useful in determining the prognosis of colorectal cancer cases.

The significance of endocan immunohistochemical expression in chronic plaque psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with immune-mediated mechanism. Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelium of blood vessels. AIMS: The present study aims to evaluate immunohistochemical localization of endocan in psoriatic skin in comparison with normal skin and to correlate its expression with the clinical and pathological data of psoriasis. PATIENTS/METHODS: Skin biopsies from 36 psoriatic patients and 40 normal subjects were taken and processed for immunohistochemical staining of endocan. RESULTS: Endocan was expressed in 63.9% and in 36.1% of epidermal keratinocytes and dermal endothelial and inflammatory cells of psoriatic skin, respectively, compared with its expression in 30% of epidermis of normal skin. Diffuse epidermal expression of endocan was in favor of cases with more angiogenesis and its intense expression was in favor of marked acanthosis and with cases affecting trunk as main presentation. Positive dermal endocan expression was significantly associated with marked parakeratosis and with more angiogenesis. CONCLUSION: Endocan is over-expressed in psoriatic skin from epidermal keratinocytes and dermal endothelial and inflammatory cells. Endocan enhances angiogenesis and proliferation of psoriatic skin contributing to pathogenic mechanisms of psoriasis.

The clinical and pathological effectiveness of microneedling and topical 5-fluorouracil in vitiligo treatment: An association with matrix metalloproteinase 2 immunohistochemical expression.

BACKGROUND: The current therapies for vitiligo require long duration with often disappointing outcomes. 5-Fluorouracil (5-FU) is a chemotherapeutic agent approved for topical use in the treatment of several dermatologic conditions. Matrix metalloproteinase 2 (MMP2) is synthesized by keratinocytes during the epidermal remodeling process and has been found to help in melanocyte migration. AIM: To investigate the efficacy and safety of flexible microneedling followed by application of 5-FU in vitiligo treatment and to evaluate the immunohistochemical expression of MMP2 in involved skin in vitiligo patients before and after treatment. METHODS: Twenty patients presented with vitiligo were planned to receive one session every 2 weeks for 12 weeks of microneedling followed by 5-FU application. Clinical response to therapy was evaluated by VASI score. Pre- and post-treatment biopsies were taken from vitiliginous patches for MMP2 immunostaining. RESULTS: Fifteen patients (75%) responded to therapy with observed side effects such as pain, erythema, and hyperpigmentation of margins. The clinical response was more in young patients and those who have short disease duration. MMP2 was significantly increased in post-treatment biopsy compared with the pretreatment one. CONCLUSIONS: 5-Fluorouracil application after microneedling is effective in the treatment of vitiligo with 75% response, 60% patient satisfaction, and tolerable side effects. The improvement in vitiligo patients by microneedling and 5-fluorouracil could be due to upregulation of MMP2 in affected vitiligo specimens.

Immunohistochemical expression of SOX2 in non-melanoma skin cancer.

BACKGROUND: Basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC) are the most common non-melanoma skin cancer (NMSC). SOX2 is a transcription factor that acts on various phases of embryonic development and its overexpression in many tumors has been reported. AIM: This work aimed to evaluate the possible role of SOX2 in pathogenesis of non-melanoma skin cancer through its immunohistochemical assessment in BCC and SCC compared to normal skin and correlating its expression with the established prognostic factors. METHODS: The investigated cases were 24 BCC, 21 SCC, and 26 normal skin specimens. RESULTS: SOX2 was not expressed in normal skin, but it was upregulated in SCC (85.7%) and BCC (66.7%), with a significant difference between malignant cases and normal skin (p < 0.001). However, SOX2 expression did not differ between SCC and BCC. SOX2 expression was associated with large-sized tumors in all malignant cases (BCC plus SCC) (p = 0.02) and in SCC (p = 0.043) alone together with its liability to be expressed in advanced stage in SCC (p = 0.063). CONCLUSIONS: SOX2 was over-expressed in cutaneous SCC and BCC without a significant difference. SOX2 may enhance progression of NMSC manifested by its association with large tumor size and advanced stage.

Stratification of urothelial bladder carcinoma depending on immunohistochemical expression of GATA3 and CK5/6.

Bladder urothelial carcinoma (BUC) has two pathways with distinct molecular features and prognosis, non-muscle invasive (NMI) and muscle invasive (MI) tumors. The aim is to investigate the expression of GATA3 and CK5/6 in BUC with correlation to clinicopathologic parameters, including their impact on survival beside their potential use to stratify cases into prognostic subgroups. This study included 80 cases of BUC stained immunohistochemically by GATA3 and CK5/6. The cases were divided into four groups regarding expression status of both markers (luminal, basal, mixed, and null). GATA3 percentage of expression decreased in urothelial carcinoma with squamous differentiation, MI tumors, high-grade tumors, tumors with involved lymph nodes, presence of perineural invasion, presence of bilharziasis, presence of lympho-vascular invasion, and high mitotic count. CK5/6 positivity was higher in urothelial carcinoma cases with squamous differentiation, MI tumors, and presence of perineural invasion. Pure urothelial carcinoma and NMI were in favor of luminal group (GATA3 +ve/CK5/6 -ve). Univariate analysis showed that the presence of bilharziasis was associated with shorter PFS (p = .04). GATA3 and CK5/6 could be used for the stratification of urothelial bladder carcinoma into subtypes with different characteristics. Luminal bladder cancer represents the most common type (60%) that carries favorable features. Bilharziasis-associated urothelial carcinoma carries poor outcome manifested by short PFS.

Effect of L-carnitine and atorvastatin on a rat model of ischemia-reperfusion injury of spinal cord.

Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1ß), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1ß, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

Evaluation of the Langerhans cells role in vitiligo and its relationship to NB-UVB.

BACKGROUND: Langerhans cells (LCs) are antigen-presenting cells that are characterized by CD1a and CD207/langerin expression. The disturbance in the communication network among keratinocytes, melanocytes, and antigen-presenting cells may be involved in vitiligo pathogenesis. AIMS: The current work aims to detect and quantify LCs in involved skin of patients affected by vitiligo before and after treatment with NB-UVB using CD1a immunohistochemistry, in addition to correlate percentage of LCs with the clinicopathological parameters. METHODS: Twenty vitiligo patients and 10 age and sex matched controls were investigated. Patients were received NB-UVB thrice weekly for 12 weeks. RESULTS: There was a significant reduction in LCs percentage in skin affected by vitiligo before treatment in comparison with normal skin. About 65% (13/20) of vitiligo patients responded to NB-UVB, and the liability to respond was correlated with LCs percentage in specimens before treatment. However, there was no statistical difference between specimens before and after treatment regarding LCs percentage. CONCLUSIONS: Reduction in LCs in vitiligo may be a sign of active disease and melanocytes destruction. The percentage of LCs affects response to NB-UVB since higher percentage is associated with greater response to therapy. Therefore, modulation of LCs as a type of immunotherapy could be beneficial in improvement of vitiligo.

The role and relationship between programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen-4 immunohistochemical expression in colorectal carcinoma patients: an impact on outcome.

BACKGROUND: Globally, colorectal carcinoma (CRC) is the third most common cancer diagnosed in both men and women. Programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are immune checkpoints that induce tumour immune escape. AIM: This study aimed to evaluate the immunohistochemical expression of PD-L1 and CTLA-4 in CRC and their relationship with clinicopathological parameters and survival data. RESULT: This study included 103 CRC, 22 adenoma and 21 non-neoplastic specimens. High PD-L1 epithelial expression was in favour of CRC and high-grade dysplastic adenoma compared to normal specimens. High PD-L1 epithelial expression was associated with larger sized tumours, perforation, advanced T stage, infiltrative tumour border configuration (TBC), high tumour budding (TB) score, low tumour-stroma ratio (TSR) and absence of peritumoural lymphocytes. High PD-L1+ tumour infiltrating lymphocytes (TILs) showed an association with absence of perforation, early T stage, pushing TBC, lower TB score, high TSR and presence of peritumoural lymphocytes. High epithelial CTLA-4 expression was in favour of adenocarcinoma, high-grade dysplastic adenoma and low-grade dysplastic adenoma compared to normal specimens. High CTLA-4 epithelial score showed an association with positive lymph nodes (LNs), presence of an infiltrative TBC and absence of peritumoural lymphocytes. Low CTLA-4+ TILs showed a significant association with advanced tumour stage and increased number of positive LNs. Prolonged survival was associated with low epithelial PD-L1 and CTLA-4, high PD-L1+ TILs and high CTLA-4+ TILs. By multivariate Cox regression analysis, PD-L1+ TILs immunoreactivity score (p = 0.020) and CTLA-4+ TILs H. score (p = 0.036) were independent prognostic factors affecting overall survival among the other prognostic factors. CONCLUSION: PD-L1 and CTLA-4 expression by tumour cells could cooperate with each other in enhancing progression of CRC leading to poor patient outcome, while their expression by TILs could stand against tumour progression.

Stratification of urinary bladder carcinoma based on immunohistochemical expression of CK5, CK14 and CK20.

Molecular subtyping of urothelial carcinoma (UC) is similar to that of breast cancer and is based on the developmental biology approach. The aim of the present study is to assess the prognostic impact of CK5, CK14, and CK20 expression in urinary bladder cancer (UBC) with the potential to stratify them into different subtypes. The current study examined the immunohistochemical expression of CK5, CK14, and CK20 in 90 specimens of UBC. CK5 was expressed in 81.1% of the cases and was significantly associated with old age, muscle invasion, presence of bilharziasis, and tendency for poor overall survival. CK20 was expressed in 47.8% of the cases and was associated with nonmuscle invasion and pure UC while 50% of the cases expressed CK14 that were associated with muscle invasion and perineural invasion. Most squamous cell carcinoma and those associated with bilharziasis were belonged to Ck5+/CK20- subgroup while pure UC and those lacked bilharziasis were located in the Ck5+/CK20+ subgroup. The basal group (Ck5+/CK14+/CK20-) showed high proliferative features compared to the intermediate group (Ck5+/CK14-/CK20-). Generally, presence of CK5 is associated with adverse features especially in the group lacking CK20; however, basal and intermediate subgroups share CK5 expression but they show different proliferative capacities, so their distinction by CK14 is helpful.

Correlation between immunohistochemical expression of Ki-67and P63 and aggressiveness of urinary bladder urothelial carcinoma.

Urothelial carcinoma is the most common urinary malignancy with a wide proportion of cancer morbidity and mortality. The aim of the present study is to evaluate Ki-67 and p63 immunoexpression and their correlation with grade and stage of bladder urothelial carcinoma. Fifty cases of bladder urothelial carcinoma were investigated and were submitted to immunohistochemical staining for p63 and Ki-67, which were assessed qualitatively and quantitatively. A high percentage of p63 immunoexpression showed a significant association with low-grade tumors (P < .05), while Ki-67 mean percentage of expression was higher in high-grade tumors, advanced stage and multiple tumors compared to low grade, early-stage and single tumors without statistical association. Furthermore, the mean percentage of p63 was higher in urothelial carcinoma with squamous differentiation compared to pure urothelial carcinoma with an absence of statistical significance. P63 could help in the identification of bladder tumors with squamous differentiation since identifying these cases is important regarding prognostic and therapeutic aspects. Ki 67 seems to be associated with features of bladder tumor progression as multiplicity, high grade and advanced stage.

Case Report: Multifocal non-invasive follicular thyroid neoplasm with papillary-like nuclear features presenting in a female child.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a separate entity by the World Health Organization in 2017 with strict inclusion and exclusion criteria.  Most NIFTP cases have been reported in adults and few cases have been diagnosed in children. Here, we present a classic case of NIFTP affecting a 10-year old female child. We also review previous reports of NIFTP in children regarding size, focality, nodal metastasis, recurrence, type of operation and follow-up data. The present report adds a new case of NIFTP in the paediatric age group characterized by multifocality, absence of nodal invasion and indolent course until last follow-up, recommending less aggressive management.

Immunohistochemical expression of BCAP 31 in chronic plaque psoriasis.

Psoriasis is a common chronic skin inflammatory disease characterized by an exaggerated proliferation of keratinocytes. B-cell receptor-associated protein 31 (BCAP 31) plays critical roles in induction of proliferation and apoptosis. The current study aimed at evaluation of the immunohistochemical localization of BCAP 31 in psoriatic skin compared to normal skin in addition of correlating BCAP31 expression with the clinical and pathological parameters of psoriasis. The present study was carried out on skin biopsies from 30 psoriatic patients and 10 normal skin (control group). BCAP31 was not expressed in normal skin either epidermis or dermis, while it was expressed in epidermis of 15 psoriatic cases and in dermis of 13 cases with a significant difference between the two groups (p < .05). Strong epidermal BCAP 31 expression was associated with marked parakeratosis (p = .025). There was a significant co-parallel epidermal and dermal expression of BCAP31 in psoriasis (p < .05). The role of BCAP 31 is not only confined to its expression by affected keratinocytes but extended to its localization to dermal lymphocytes where they were correlated with each other. The up- regulation of BCAP 31 in psoriatic lesion compared to normal skin may suggest its use as a target therapy for treatment of psoriasis that necessitates further studies to clarify.

Tumour-infiltrating Langerhans cells in non-melanoma skin cancer, a clinical and immunohistochemical study.

Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represents 78.5% of all skin malignant tumours in Egypt. Dendritic cells can be found in almost all human tumours, they play an important role in antitumour immunity. The aim of the present study was to evaluate the percentage of Langerhans cells using CD1a in non-melanoma skin cancer, including BCC and SCC and to correlate this percentage with their clinicopathological features. The current study was performed on surgically excised specimens of 41 patients presented with non-melanoma skin cancer (26 BCC and 15 SCC) and 16 healthy volunteer control subjects. The mean and median percentage of Langerhans cells were higher in normal epidermis of control compared to malignant tumour tissue (p < 0.0001) and adjacent epidermis overlying malignant tumour tissue (p = 0.007). Langerhans cells were significantly seen in BCC cases more than SCC (p = 0.035) and they were seen in facial lesions more than those arising from other sites (p = 0.007). The reduction of Langerhans cells is a way for non-melanoma skin cancer to develop and progress. Marked reduction of Langerhans cells in SCC compared to BCC could refer to their role as a barrier against metastasis.

Hepatoprotective effect of artichoke leaf extracts in comparison with silymarin on acetaminophen-induced hepatotoxicity in mice.

Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.Abbreviation: ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.

Fine-Needle Aspiration Cytology of Follicular Dendritic Cell Sarcoma of Cervical Lymph Node: A Challenging Diagnosis.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor that could arise in both nodal and extranodal sites, with only nine previously reported cases demonstrating cytologic features. In this report, we describe a case of FDCS in a 60-year-old female who presented with neck mass. Fine-needle aspiration cytology and subsequent core biopsy were suggestive of metastatic carcinoma. The cytologic features were epithelioid-to-spindle cell morphology, vesicular nuclei, prominent nucleoli, intranuclear inclusions, and occasional binucleated and multinucleated forms. However, absence of cytokeratin expression was against the diagnosis of metastatic carcinoma. The definitive diagnosis was reached by the demonstration of CD21 and CD23 expression. The pathologist should be aware of this rare malignant tumor, especially its cytologic features in aspirated material. The differential diagnosis in the above case was metastatic carcinoma, melanoma, and malignant granular cell tumor. The demonstration of expression of one or more dendritic cell marker is the clue for the diagnosis, which could be applied on cytological preparations with sufficient material.

Diagnostic Value of TROP-2 and CK19 Expression in Papillary Thyroid Carcinoma in Both Surgical and Cytological Specimens.

Papillary thyroid carcinoma (PTC) represents the most common primary malignant thyroid tumor and its diagnosis is dependent on the presence of classic nuclear features that are sometimes seen in some non-neoplastic and benign lesions. Several immunohistochemical markers are used individually or in combination to help in differentiation of PTC from mimickers. The aim of the current study was to assess the diagnostic value of TROP-2 and cytokeratin 19 (CK19) expression in differentiating PTC from other mimickers both singly and in combination. The current study was carried out on 77 surgical specimens (56 PTC and 21 non-neoplastic cases) and 12 cytological specimens (4 THY2, 6 THY4, and 2 THY5). TROP-2 was negative in 81% of non-neoplastic surgical specimens and in 100% of THY2 cytological specimens while it was positive in 71.4% of PTC surgical specimens and 100% of THY4/THY5 cytological specimens. Sensitivity and specificity of TROP-2 positive expression for diagnosis of PTC in surgical specimens reached 71% and 81%, respectively, while it reached 100% for both in cytological specimens. Cytokeratin 19 showed positive expression in 85.7% of non-neoplastic surgical specimens and in 92.9% of PTC surgical specimens. Cytokeratin 19 showed negative expression in 75% of Thy2 cases while it was positive in all studied Thy4 and Thy5 cases. Sensitivity and specificity of CK19 total estimated score for diagnosis of PTC in surgical specimens were 78.6% and 66.7%, respectively, while it reached 100% and 75% in cytological specimens. Positive TROP-2 and CK19 expression in PTC were associated with lymph node metastasis. TROP-2 is a specific rather than sensitive marker while CK19 is a sensitive rather than specific marker in differentiating PTC from other mimickers in surgical specimens. The diagnostic validity of both markers was superior in diagnosis of classic PTC compared with follicular variant PTC. TROP-2 is superior to CK19 in diagnosis of PTC in cytological specimens. Both TROP-2 and CK19 could be used preoperatively in adjunct to hematoxylin and eosin for more confident diagnosis of thyroid cytology and along with radiology as predictors of lymph node metastasis.