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Background: Basal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis. Objective: This study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy. Methods: A total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants. Results: Dermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker. Conclusions: The lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques. [ABSTRACT FROM AUTHOR]

Abstract Background Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease. Methods We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022. Results The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via computed tomography (CT) (n = 10, 66.67%) or magnetic resonance imaging (MRI) (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients. Conclusions Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions.

Adverse drug reactions, multiple drug allergy syndrome, and multiple drug intolerance syndrome, are common terms used in clinical practice worldwide. Here we present a 61-year-old Caucasian female, who is diabetic and hypertensive, and started receiving doxycycline for an upper respiratory tract infection. Simultaneously, she selfprescribed Advil.®. The patient has had a previous episode of drug intolerance. In this episode, she presented with a skin rash included bullae on her arms, legs and in part of her abdomen along with some systemic symptoms such fever, cough, and upset stomach. Biopsies for hematoxylin and eosin (H&E), direct immunofluorescence (DIF), and immunohistochemistry (IHC) stain analysis were performed. The diagnosis was made based upon interpretation of the histology in the context of drug reaction with alterations on the dermal lymphatics. DIF showed significant deposits of fibrinogen, complement/C3c and IgA around the dermal vessels, and at the endothelial-mesenchymal dermal cell junctions. IHC staining showed lymphangiectases with strong staining of the lymphatic junctions to the adjacent upper dermis using D2-40 marker. In this case, it is possible that the drug reaction could be causing previously unreported damage in lymphatics, including fragmentation and dilatation. These channels are stimulated inhibited, contracted, and relaxed by interactions with multiple receptors and the inflammation could cause dysregulation in those including their shape. [ABSTRACT FROM AUTHOR]

Background: Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease. Methods: We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022. Results: The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via computed tomography (CT) (n = 10, 66.67%) or magnetic resonance imaging (MRI) (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients. Conclusions: Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions. [ABSTRACT FROM AUTHOR]

Ovarian lymphangioma, a rare pathologic finding, is an ovarian mass characterized by lymphatic tissue lined with endothelial cells. It is normally asymptomatic and may be found incidentally during abdominal surgery for other pathologies.This report describes a case of a 49-year-old woman presenting to her primary care physician for three months of abdominal bloating and irregular menses. Magnetic resonance imaging revealed a 31 × 23 × 20 cm uterine mass suspected to be the cause of her symptoms. Total abdominal hysterectomy and bilateral salpingectomy were performed. During surgery, the right ovary was flattened and densely adhered to the body of the uterus, necessitating right oophorectomy. Pathology of the right ovary revealed flattened endothelial cells lining cystic spaces, consistent with the diagnosis of ovarian lymphangioma. Taken together, this case and the literature suggest that ovarian lymphangioma should be considered in the differential of ovarian masses, and their management shared more widely to help encourage the development of standard practice guidelines. There are no clear guidelines for when, and how often, to monitor these lesions after resection. In this case, the patient was seen at two-week and six-week follow-up visits with no new symptoms. Given that some case reports describe malignant transformation, patients should be followed this closely in the post-surgical period, and the best cadence for follow-up should be determined to improve outcomes.

Background: Venous malformations (VMs) are distinguished from lymphatic malformations (LMs) when specific diagnostic skin lesions are present. In the deep type, this is difficult by clinico‐radiologic evaluation alone. We aimed to investigate the usefulness of lymphatic vessel endothelial cell (LEC) markers for the differential diagnosis of the deep VMs and LMs. Methods: A retrospective study was conducted based on the medical records of patients with VMs and LMs who underwent biopsy with both D2‐40 and PROX‐1 immunohistochemistry. We compared the initial clinico‐radiological diagnosis with the final pathological diagnosis and identified which ones showed a difference. Results: From 261 patients who had VMs and LMs, 111 remained after the exclusion of those who showed definite surface diagnostic features. After pathological diagnosis with the expressions of D2‐40 and PROX‐1, 38 of 111 (34.2%) patients' final diagnoses were changed. Among these 38 cases, diagnosis was not changed by D2‐40 positivity alone, but changed by PROX‐1 positivity alone (52.6%) or by both (47.4%). The diagnostic changes were more frequent in the deep category (43.7%) than in the superficial category. Conclusions: Identifying the expression of D2‐40, and especially PROX‐1, in the differential diagnosis of VMs and LMs may provide important treatment guidelines and understanding their natural course. [ABSTRACT FROM AUTHOR]

The article examines ectopic germinal centers (GCs) in Sjögren's syndrome (SS) and non-SS non-sicca patients, revealing similarities in GC frequency. Topics discussed include the significance of GCs in SS severity, the diagnostic implications of marker expression differences, and the histomorphological variations between the two patient populations.

Introduction: Blue rubber bleb nevus syndrome (BRBNS) is an uncommon vascular anomaly characterized by multifocal cutaneous, visceral, and other soft tissue or solid organ venous malformations. We observed that BRBNS lesions express immunohistochemical markers of lymphatic differentiation. Methods: BRBNS histopathologic specimens assessed at our institution during the past 27 years were reviewed. Slides from 19 BRBNS lesions were selected from 14 patients (9 cutaneous, 9 gastrointestinal, and 1 hepatic). We recorded the involved anatomical compartments and presence/absence of thrombi or vascular smooth muscle. Immunohistochemical endothelial expression of PROX1 (nuclear) and D2-40 (membranous/cytoplasmic) was evaluated semi-quantitatively. Results: Endothelial PROX1 immunopositivity was noted in all specimens; the majority (89.5%) demonstrated staining in more than 10% of cells. D2-40 immunopositivity was present in one-third (33%) of cutaneous lesions and only 1 gastrointestinal lesion. Conclusion: Endothelial cells in BRBNS almost always express 1 or more immunohistochemical markers of lymphatic differentiation. [ABSTRACT FROM AUTHOR]

BackgroundBasal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis.ObjectiveThis study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy.MethodsA total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants.ResultsDermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker.ConclusionsThe lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques.

Ankita Sharma, Srikant Natarajan, Nidhi Manaktala, Karen Boaz, Nandita KP, Amitha Lewis, Shweta Yellapurkar Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaCorrespondence: Karen Boaz, Department of Oral Pathology, Manipal College of Dental Sciences Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India, Email karen.boaz@manipal.eduIntroduction: Nomograms are proven in “individualized risk prediction” in sarcomas and breast and prostate cancers. Incorporating immunohistochemical markers and histopathological parameters can enhance accuracy of these graphical representations of statistical predictive models concerning metastasis. D2-40, a monoclonal antibody to podoplanin (regulator of motility expressed in malignant epithelial cells), dually predicts metastatic potential of tumour by estimating the motile tumour phenotype and by detecting lymphatic vessels/density, both essential to metastasis in OSCC. Thus, we propose a model that incorporates D2-40 immunostaining of individual tumour cells (ITC) too with other variables (seen in H+E staining) as a predictive nomogram.Methods: Sixty cases of OSCC were selected with equal number of cases (n=30) of pN0 and pN+ status. Bryne’s grading of invasive front of tumour (ITF) was done on H+E-stained slides followed by D2-40 immunostaining for ITCs at ITF and lymphatic vessels. Multivariate regression analysis was used to generate the nomogram of LNM where the predictive contribution of each covariate, namely depth of invasion, D2-40-stained ITCs, gender, histological grade, and worst pattern of invasion (WPOI), was plotted on a scale of 1– 100 points.Results: The nomogram showed that the strongest variable in OSCC was the WPOI in H+E-stained section followed by D2-40-positive ITCs and gender.Discussion: Our predictive nomogram for LNM in OSCC surprisingly showed that a tumour with lower score of WPOI (islands vs ITC) showed numerous D2-40-positive ITCs, drastically increasing the probability of metastasis. The concept of “individualized risk prediction” can be used to predict lymph node metastasis using a variety of histopathological criteria that can be visualized in routine and immunohistochemical staining in OSCC with the aid of a nomogram.Keywords: nomogram, individualized risk prediction, D2-40, lymph node metastasis in OSCC, podoplanin

Background: Claudins are a clan of proteins that are the most important component of tight junctions. The claudin-4 expression has been linked to tumour cell invasion and progression in a variety of primary malignancies. Evaluation of lymphovascular density (LVD) correlates with tumour aggressiveness and may correlate with prognosis. D2-40 is a highly specific marker of lymphatic vessels. Aims: To evaluate the claudin-4 expression in relation to LVD by D2-40 expression and with clinicopathological parameters in prostatic adenocarcinoma. Settings and Design: Prospective study Materials and Methods: 39 cases of prostatic adenocarcinoma were taken, the D2-40 and claudin-4 immunohistochemical stains were performed and correlation was done with clinicopathological parameters. Statistical Analysis Used: Statistical analyses such as mean, median, standard deviation, Mann–Whitney U test, Fischer exact test, Spearman's rank-order correlation coefficient, Chi-square test and T-test were used. Results: The claudin-4 expression was seen higher in cases with higher Gleason score but it was statistically non-significant (P = 0.778). The claudin-4 expression did not correlate with any clinicopathological parameters. LVD in the peritumoral area was significantly higher as compared to the intratumoral area (P = 0.005). Intratumoral LVD and perineural invasion were found to be statistically significant (P = 0.048). Conclusion: The claudin-4 expression may correlate with adverse prognostic parameters. Higher lymphatic vessels can be responsible for the higher metastatic potential of prostatic adenocarcinomas. [ABSTRACT FROM AUTHOR]

Preoperative prediction of LVI status can facilitate personalized therapeutic planning. This study aims to investigate the efficacy of preoperative MRI-based radiomics for predicting lymphatic vessel invasion (LVI) determined by D2-40 in patients with invasive breast cancer. A total of 203 patients with pathologically confirmed invasive breast cancer, who underwent preoperative breast MRI, were retrospectively enrolled and randomly assigned to the following cohorts: training cohort (n =141) and test cohort (n =62). Then, univariate and multivariate logistic regression were performed to select independent risk factors and build a clinical model. Afterwards, least absolute shrinkage and selection operator (LASSO) logistic regression was performed to select predictive features extracted from the early and delay enhancement dynamic contrast-enhanced (DCE)-MRI images, and a radiomics signature was established. Subsequently, a nomogram model was constructed by incorporating the radiomics score and risk factors. Receiver operating characteristic curves were performed to determine the performance of various models. The efficacy of the various models was evaluated using calibration and decision curves. Fourteen radiomics features were selected to construct the radiomics model. The size of the lymph node was identified as an independent risk factor of the clinical model. The nomogram model demonstrated the best calibration and discrimination performance in both the training and test cohorts, with an area under the curve of 0.873 (95% confidence interval [CI]: 0.807-0.923) and 0.902 (95% CI: 0.800-0.963), respectively. The decision curve illustrated that the nomogram model added more net benefits, when compared to the radiomics signature and clinical model. The nomogram model based on preoperative DCE-MRI images exhibits satisfactory efficacy for the noninvasive prediction of LVI determined by D2-40 in invasive breast cancer. [ABSTRACT FROM AUTHOR]

Papillary intralymphatic angioendothelioma (PILA) is an extremely rare vascular tumor and its pathogenesis is unknown. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) is a heterogeneous group of disorders caused by mosaicism for activating mutations of PIK3CA and characterized by asymmetric overgrowth, skeletal anomalies, skin lesions, and vascular malformations. An association between PILA and PROS has not been known. We report a case of PILA involving the spleen of a young girl with the clinical and molecular diagnosis of PROS. Sequencing of the patient's germ-line DNA detected a pathogenic PIK3CA variant c.1357G>A in 10.6% of alleles. Splenectomy revealed a 4-cm tumor composed of ectatic lymphatics with intraluminal papillary projections, consistent with PILA. The tumor cells showed immunohistochemical expression of CD31, CD34, ERG, FLI-1, PROX1, and caldesmon, while D2-40 was negative. The latter may suggest that the tumor derived from an endothelial precursor arrested in the final steps of lymphothelial differentiation, in keeping with the known role of the PIK3CA -governed molecular pathway in the progression of vascular progenitors to mature endothelial cells. The data implicates PIK3CA in the pathogenesis of PILA and broadens the spectrum of phenotypic expressions of PROS. [ABSTRACT FROM AUTHOR]

Background: The presence of lymph-vascular space invasion is a powerful predictor of lymph node metastasis. However, most studies do not distinguish lymph vessel invasion (LVI) and blood vessel invasion (BVI). The aim of this study was to distinguish the role of LVI and BVI in lymphatic metastasis and recurrence in patients with endometrial cancer. Methods: We examined 171 patients with endometrial cancer. Immunohistochemical double staining was used to distinguish lymphatic invasion and vascular invasion. First, the relationship between lymphatic/vascular invasion and clinicopathological features and lymphatic metastasis was studied. Then, the expression of D2-40/LVI and CD31/BVI in patients with recurrence was analyzed. Results: Pathological grading (G3) and D2-40/LVI were independent high-risk factors for lymph node metastasis of endometrial cancer. The area under the receiver operating characteristic curve values for predicting lymphatic metastasis using pathological grading (G3) or D2-40/LVI alone were.642 and.680, respectively, and the area under the curve value for the combined detection of pathological grading (G3) and D2-40/LVI was.726, which was greater than the values obtained for the abovementioned independent variables. Among the 15 recurrent patients, 5 (33.3%) were D2-40/LVI positive, 2 (13.3%) were CD31/BVI positive, and 8 (53.3%) were both D2-40/LVI and CD31/BVI positive. Conclusion: D2-40/LVI combined with G3 can effectively predict lymph node metastasis of endometrial carcinoma. [ABSTRACT FROM AUTHOR]

BACKGROUND: The presence of lymph-vascular space invasion is a powerful predictor of lymph node metastasis. However, most studies do not distinguish lymph vessel invasion (LVI) and blood vessel invasion (BVI). The aim of this study was to distinguish the role of LVI and BVI in lymphatic metastasis and recurrence in patients with endometrial cancer. METHODS: We examined 171 patients with endometrial cancer. Immunohistochemical double staining was used to distinguish lymphatic invasion and vascular invasion. First, the relationship between lymphatic/vascular invasion and clinicopathological features and lymphatic metastasis was studied. Then, the expression of D2-40/LVI and CD31/BVI in patients with recurrence was analyzed. RESULTS: Pathological grading (G3) and D2-40/LVI were independent high-risk factors for lymph node metastasis of endometrial cancer. The area under the receiver operating characteristic curve values for predicting lymphatic metastasis using pathological grading (G3) or D2-40/LVI alone were .642 and .680, respectively, and the area under the curve value for the combined detection of pathological grading (G3) and D2-40/LVI was .726, which was greater than the values obtained for the abovementioned independent variables. Among the 15 recurrent patients, 5 (33.3%) were D2-40/LVI positive, 2 (13.3%) were CD31/BVI positive, and 8 (53.3%) were both D2-40/LVI and CD31/BVI positive. CONCLUSION: D2-40/LVI combined with G3 can effectively predict lymph node metastasis of endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background Benign multicystic peritoneal mesothelioma (BMPM) is a benign tumor that usually occurs in middle-aged females. Although several published studies have reported the occurrence of this tumor in the abdominal cavity, few have documented its development in the inguinal region. Case presentation We present a case of a 48-year-old female presenting with a bulge in her left inguinal region. Physical examination revealed a golf ball-sized nodule in the left inguinal region that could not be pushed back into the abdominal cavity. Contrast-enhanced computed tomography showed a multicystic tumor; therefore, the patient was diagnosed with inguinal hernia or hydrocele of the Nuck’s canal. We performed surgical resection and hernia repair using the mesh plug method. The resected specimen was 80 mm in length and contained a multicystic tumor. Pathological examination showed that the cyst wall was lined by a single layer of cuboidal to single layer squamous epithelium. Immunohistochemistry revealed positivity for calretinin in the epithelial cells, for which a diagnosis of BMPM was established. The patient returned to our hospital after 5 years with symptoms similar to the previous episode, but this time in the right inguinal region. Imaging studies showed a tumor in the right inguinal region with the same characteristics as the previous one. The patient underwent tumor resection and hernia repair using the same technique. The resected tumor was 45 mm in length and had characteristics similar to the previously resected tumor. The presence of calretinin and D2-40 on immunohistochemistry led to the diagnosis of BMPM. There was no recurrence of BMPM for 33 months after the secondary surgery. Conclusions Here we present the first report of metachronous BMPM occurring in bilateral inguinal canals. Although the pathogenesis of BMPM remains unclear, reactive changes have been suggested to cause tumors originating from the groin. The treatment of choice for BMPM is surgical resection. For diagnosis, pathological examination with immunostaining can be useful. The most appropriate postoperative follow-up for inguinal BMPM is controversial, and the accumulation of more inguinal BMPM cases is needed.

Uterine tubes (UTs) are essential during physiological reproduction. The most intriguing part of its wall is the mucosa. Apart from the epithelial cells vital for its normal function, the connective tissue lamina propria contains wide spaces whose function, morphology and structure are yet to be elucidated. The present study used bioptic samples from 25 premenopausal (mean age 48.3 years, s=3.56) and 25 postmenopausal women (mean age 57.8 years, s=7.79). In both study groups, samples were obtained from two anatomically distinct parts of the UT - ampulla and infundibulum with fimbriae. The specimens were processed for scanning electron microscopy (SEM) and immunohistochemical detection of podoplanin (clone D2-40) and VEGFR-3 - two markers of lymphatic endothelial cells. The results showed that specimens from premenopausal and postmenopausal women contain wide lymphatic spaces, also known as lymphatic lacunae. The most probable function of the lacunae in the fimbriae is oocyte pick-up upon ovulation thanks to their ability to get engorged with lymph, thus serving as an erectile-like tissue. The ampullary lacunae are probably responsible for tubal fluid maintenance and recirculation. These results indicate that they are vital for normal reproduction because tubal fluid dynamics are as important as fluid composition. Further research on this topic is highly warranted because more detailed insights into UT function have a great potential to refine the methods of reproductive medicine, e.g. in vitro fertilization (IVF), which are still far from optimal regarding fertility outcomes. [ABSTRACT FROM AUTHOR]

Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country.Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution.Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review.Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2-40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs.Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications. [ABSTRACT FROM AUTHOR]

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study., (© 2024 Wiley Periodicals LLC.)

Abstract Background Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS.

Follicular dendritic cell sarcoma is a rare histiocytic and dendritic neoplasm mainly involving the lymph nodes and selective extranodal sites. They are often misdiagnosed due to nonspecific clinical, radiological, and morphological findings in addition to their rarity. Four cases described below had variable age of presentation, site of involvement, size of the lesion, and histopathological features. Application of an extensive immunohistochemical panel, including a combination of >1 dendritic cell marker, clinched the diagnosis. A combination of D2-40 and Cluster of differentiation 21 (CD21) worked best in establishing a definite role in the current series. Programmed death-ligand 1 (PD-L1) analysis was positive in two of the three cases where it could be performed. However, none of our cases had received immunotherapy. Prompt recognition of the described histopathology features and incorporation of novel immunohistochemical markers can translate to timely initiation of therapy for this aggressive disease. [ABSTRACT FROM AUTHOR]

Background/Aims: Colorectal cancer (CRC) patients often exhibit peritoneal metastasis, which negatively impacts their prognosis. CD31 and D2-40 have recently been suggested to be predictors of breast cancer prognosis, but their role in colorectal peritoneal metastasis (CRPM) remains unknown. Methods: The expression profiles of CD31 and D2-40 were analyzed in CRC patients with or without CRPM and in CRC cell lines with increasing metastatic potential. Overexpression and short hairpin RNA knockdown assays were performed in CRC cells, and the effects of these alterations on epithelial-mesenchymal transition (EMT) in vitro, growth of xenograft tumors in vivo, and peritoneal metastasis potential in a mouse model of CRPM were examined. Results: The expressions of CD31 and D2-40 were upregulated in CRC tumor tissues and was elevated further in tumor tissues from patients with CRPM. CD31 and D2-40 expression levels exhibited increasing trends parallel to the EMT potential of CRC cells. CD31 and D2-40 are essential for CRC cell EMT in vitro as well as for xenograft tumor growth and peritoneal metastasis in vivo. Conclusions: CD31 and D2-40 contribute to CRPM by promoting EMT and may serve as prognostic markers and therapeutic targets for CRC, particularly in patients with peritoneal metastasis.

Abstract Background The aims of this study were to determine intra (ILVD) and peritumoral (PLVD) lymphatic vessel density (LVD), and to investigate the relationship of LVD with occult metastasis and prognosis. Methods Eighty-seven oral squamous cell carcinomas, in clinical stages I or II, arising in the tongue or floor of the mouth were stained with podoplanin. Lymphatic vessels were quantified in intra and peritumoral areas by sequential analysis and hot spot evaluation. Associations of the ILVD and PLVD with clinicopathologic parameters were determined by Chi-square or Fisher’s exact test. The 5 and 10-year survival rates were calculated by the Kaplan–Meier and compared using the log-rank test. Results No significant association was observed between ILVD or PLDV and clinicopathologic variables including occult lymph node metastasis, or clinical follow-up. However, ILVD showed a significant association with regional recurrence (p = 0.040). The perineural invasion was associated with PLVD (p = 0.041). Disease-specific (p = 0.044) and disease-free survivals (p = 0.016) had significant association with PLVD. Conclusions The intra or peritumoral lymphatic vessel density had no predictive value for occult lymph node metastasis in the early stages of oral cancer arising in the tongue or floor of mouth.

Background Kaposi sarcoma (KS) is a low-grade malignant vascular neoplasm, whose etiology is associated with human herpes virus 8 (HHV8). Owing to its broad clinicopathological spectrum, KS mimics a variety of non-KS vascular lesions both clinically and histologically, thus posing a diagnostic challenge. Immunohistochemical markers are needed to confirm diagnosis. Objective To study the sensitivity and specificity of D2-40 in comparison with HHV8-latent nuclear antigen 1 to identify KS among other cutaneous vascular proliferative lesions. Patients and methods The present study was carried out on 50 cases with cutaneous vascular proliferation. Examination of hematoxylin and eosin-stained sections was done for all cases to verify the diagnosis. Additional sections of all cases were subjected to immunohistochemical stains for the following primary antibodies: HHV8 and D2-40 monoclonal antibody. Results The study included 19 KS cases and 31 non-KS. Among KS lesions 15.8% were patch stage, 26.3% plaque stage, 36.84% nodular stage, 10.5% pyogenic granuloma-like KS, and 10.5% intravascular KS. All KS cases stained positive for HHV8-latent nuclear antigen 1, whereas none of other vascular lesions showed positive staining. Immunohistochemistry using D2-40 showed positive staining in 70% (n=35) and negative staining in 30% (n=15) of the total cases. All KS lesions expressed D2-40 in both endothelial lining and spindle cells. A total of 16 cases of non-KS vascular lesions expressed D2-40 in endothelial lining only. D2-40 positivity of both endothelial lining and spindle cells was found to be equally sensitive and specific to HHV8 for diagnosis of KS. Conclusion D2-40 positivity of both vascular lining and spindle cells can be considered both sensitive and specific stain to differentiate KS from other vascular lesions.

Podoplanin (PDPN) is a specific marker for lymphatic endothelial cells; however, it can be expressed by many other cells including renal podocytes. In dermatology, PDPN has been involved in diverse disorders, such as tumor lymphangiogenesis, as well as in immune-mediated disorders. Herein, we illustrate and discuss the landscape of PDPN in dermatology.

Background: Benign multicystic peritoneal mesothelioma (BMPM) is a benign tumor that usually occurs in middle-aged females. Although several published studies have reported the occurrence of this tumor in the abdominal cavity, few have documented its development in the inguinal region. Case presentation: We present a case of a 48-year-old female presenting with a bulge in her left inguinal region. Physical examination revealed a golf ball-sized nodule in the left inguinal region that could not be pushed back into the abdominal cavity. Contrast-enhanced computed tomography showed a multicystic tumor; therefore, the patient was diagnosed with inguinal hernia or hydrocele of the Nuck's canal. We performed surgical resection and hernia repair using the mesh plug method. The resected specimen was 80 mm in length and contained a multicystic tumor. Pathological examination showed that the cyst wall was lined by a single layer of cuboidal to single layer squamous epithelium. Immunohistochemistry revealed positivity for calretinin in the epithelial cells, for which a diagnosis of BMPM was established. The patient returned to our hospital after 5 years with symptoms similar to the previous episode, but this time in the right inguinal region. Imaging studies showed a tumor in the right inguinal region with the same characteristics as the previous one. The patient underwent tumor resection and hernia repair using the same technique. The resected tumor was 45 mm in length and had characteristics similar to the previously resected tumor. The presence of calretinin and D2-40 on immunohistochemistry led to the diagnosis of BMPM. There was no recurrence of BMPM for 33 months after the secondary surgery. Conclusions: Here we present the first report of metachronous BMPM occurring in bilateral inguinal canals. Although the pathogenesis of BMPM remains unclear, reactive changes have been suggested to cause tumors originating from the groin. The treatment of choice for BMPM is surgical resection. For diagnosis, pathological examination with immunostaining can be useful. The most appropriate postoperative follow-up for inguinal BMPM is controversial, and the accumulation of more inguinal BMPM cases is needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: The presence of lymph-vascular space invasion is a powerful predictor of lymph node metastasis. However, most studies do not distinguish lymph vessel invasion (LVI) and blood vessel invasion (BVI). The aim of this study was to distinguish the role of LVI and BVI in lymphatic metastasis and recurrence in patients with endometrial cancer. METHODS: We examined 171 patients with endometrial cancer. Immunohistochemical double staining was used to distinguish lymphatic invasion and vascular invasion. First, the relationship between lymphatic/vascular invasion and clinicopathological features and lymphatic metastasis was studied. Then, the expression of D2-40/LVI and CD31/BVI in patients with recurrence was analyzed. RESULTS: Pathological grading (G3) and D2-40/LVI were independent high-risk factors for lymph node metastasis of endometrial cancer. The area under the receiver operating characteristic curve values for predicting lymphatic metastasis using pathological grading (G3) or D2-40/LVI alone were .642 and .680, respectively, and the area under the curve value for the combined detection of pathological grading (G3) and D2-40/LVI was .726, which was greater than the values obtained for the abovementioned independent variables. Among the 15 recurrent patients, 5 (33.3%) were D2-40/LVI positive, 2 (13.3%) were CD31/BVI positive, and 8 (53.3%) were both D2-40/LVI and CD31/BVI positive. CONCLUSION: D2-40/LVI combined with G3 can effectively predict lymph node metastasis of endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence of Barrett’s esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA. Methods We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2–40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment. Results H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2–40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively. Conclusions Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.

Lymphangiogenesis makes an important contribution to the tumour microenvironment (TME), but little is known about this in oral squamous cell carcinoma (OSCC). Archival formalin‐fixed paraffin‐embedded specimens (28 OSCC, 10 inflamed and 6 normal oral mucosa controls) were processed using immunohistochemistry (IHC) with antibodies against lymphatic markers D2‐40 (podoplanin), LYVE‐1, VEGFR3 and Prox1. After the endothelial cells had been highlighted by the various markers for lymphatic endothelium, the positive stained cells and vessels were identified and counted in a systematic manner to determine microvessel density. Double‐labelling immunofluorescence (DLIF) was used to investigate the specificity of D2‐40 and LYVE‐1 to lymphatic endothelial cells (LECs) as opposed to blood ECs. There was higher D2‐40 and Prox1 lymphatic vessel density (P =.001) in the OSCC group when compared with both control groups. Some malignant keratinocytes expressed lymphatic markers, as did a much smaller number of epithelial cells in the control groups. DLIF showed that no vessels co‐expressed D2‐40/CD34 or LYVE/CD34. Some D2/40+ LVs were LYVE−. D2‐40 was the most specific LEC marker in OSCC tissues. These results establish that the OSCC TME contains significantly more lymphatic vessels expressing D2‐40 and Prox1 than the control groups, which may play a role in facilitating lymphatic invasion and metastases. [ABSTRACT FROM AUTHOR]

Background: Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods: A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results: The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions: Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS. [ABSTRACT FROM AUTHOR]

Angiogenesis is an important issue related to normal growth and differentiation, and it is a critical issue in the progression of human disease in oral mucosa. Tooth marks occur after clenching the teeth for a long period under muscle tension in the human oral cavity. However, the sites of angiogenesis, cell differentiation and microvessel density are not known for human mucosa with tooth marks. Therefore, we investigated the relationship between the markers of differentiation (Ki-67), angiogenesis (CD31, D2-40, VEGF-A), and marks from teeth in the second molar region using immunohistochemical methods. In addition, we compared these areas with the mucous membrane. Our results revealed blood and lymphoid vessels in irregular mucosa structures, and the vessels in the oral mucosa were observed in three types of samples: dentulous, denture attachment (containing partial teeth), and edentulous samples. The localization of the angiogenesis was related to the structure of the oral mucosa of connective tissue in humans, such as the mucosal fold-like of the buccal region. Using principal component analysis (PCA), we found that tooth occlusal condition, gender, anti-VEGF-A reaction levels in oral mucosa of the epithelium were positive factors in all groups, which is in contrast to the negative association of Ki-67 reaction in the epithelium and CD31 expression. In addition, Ki-67 reaction in oral mucosa had negative impacts, in contrast to the positive association of D2-40. These PCA properties provide useful information for future study of tumour progression or mechanical stress in remodelling of oral mucosa and angiogenesis. Moreover, mechanical stress of the occlusal condition may be correlated with tumour angiogenic activity and cell differentiation in human oral mucosa.

Context: Lymphangiogenesis correlates with poor prognosis in Invasive Ductal Carcinoma (IDC) breast. D2-40 antibody, a specific marker for lymphatic endothelium, differentiates lymphatic from vascular endothelium. Therefore, the aims of this study were to estimate lymphangiogenesis using D2-40 antibody and correlate with lymphatic invasion (LI) and axillary lymph node (LN) status and compare lymphatic mean vessel density (LMVD) with Tumor (T) and Node (N) stages and grade of tumor. Methods and Material: The study was conducted on fifty consecutive cases of IDC breast who underwent modified radical mastectomy (MRM) from Jan 2009 to March 2011. Hematoxylin-eosin sections and Immunohistochemistry (IHC) slides were studied along with their LN status. LMVD was counted after D2-40 immunostaining (100x magnification) in three hot spots in peritumoral areas and averaged. LI as opposed to vascular invasion (BVI), and LN status for all cases were assessed. Statistical Analysis: Statistical analysis was done using SPSS software (version 14.0 for Windows). Pearson's correlations, χ2 tests and Mann-Whitney U test were used. Results: Lymphangiogenesis varied from 0 to 58 with mean LMVD of 11. Of 50 cases, five showed no lymphatic vessels in peritumoral areas; of these five, three had positive LNs. 21/50 cases had LI. No statistical significant association was seen between lymphangiogenesis and LI. 34/50 cases had positive LNs. Mean LMVD was higher in patients with N2/N3 stage as compared to N0/N1 stage and was statistically significant (P = 0.013). Conclusions: D2-40 is specific marker for lymphatic endothelium. LI and lymphangiogenesis, as opposed to BVI, are better prognostic indicators in IDC breast.

Composite hemangioendothelioma is a rare vascular tumor morphologically comprising several distinct vascular components and exhibits a borderline malignant potential. We described the case of a 53-year-old female who presented with an infiltrative mass in the paravertebral soft tissue. The tumor showed discrete nests of synaptophysin-expressing epithelioid cells accompanied by rich vasculature, features highly reminiscent of sympathetic paraganglioma. Further analysis revealed areas resembling spindle cell hemangioma, retiform hemangioendothelioma, cavernous hemangioma/lymphangioma, and epithelioid hemangioendothelioma without the myxohyaline matrix in the tumor, and a final diagnosis of composite hemangioendothelioma with synaptophysin expression was made. Critical appraisal of this recently described entity and its possible pathogenic relationship with retiform hemangioendothelioma were discussed. [ABSTRACT FROM AUTHOR]

There are several clinicopathological factors associated with the prognosis of cutaneous squamous cell carcinomas (cSCC), but there remains a lack of molecular markers associated with cSCC tumor progression. This study aimed to determine the association between histopathological prognostic parameters and tumoral podoplanin expression in cSCC. This study included 63 paraffin embedded cSCC samples that were evaluated for tumoral podoplanin expression using immunohistochemistry. Among the 63 tumor samples, 27% lacked podoplanin expression, 22% exhibited diffuse podoplanin expression, and 51% exhibited focal podoplanin expression. Tumoral podoplanin expression was correlated with lymphovascular invasion and lymph node metastasis (p value < 0.05, for both). Additional research is needed to further delineate how the tumoral podoplanin expression can be used as a prognostic marker in patients with cSCC. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Barrett's esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA.Methods: We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2-40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment.Results: H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2-40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively.Conclusions: Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens. [ABSTRACT FROM AUTHOR]

Aims: Lymphatic invasion (LI) and venous invasion (VI) are the strongest risk factors for lymph node metastasis in patients with early gastric cancer, and may predict their prognosis. We aimed to investigate interobserver agreement among pathologists before and after adding ancillary staining for diagnosing LI and VI in this setting. Methods and results: This retrospective study included 100 specimens of submucosal invasive gastric cancer from 100 patients treated using endoscopic resection. Three pathologists (expert, intermediate and trainee experience levels) independently evaluated individual LI and VI status using haematoxylin and eosin (H&E)‐stained slides, and re‐evaluated their decisions by reviewing corresponding D2‐40‐stained and elastin‐stained slides. Interobserver agreement was assessed using κ statistics. With the ancillary D2‐40 staining, there was an improved agreement for LI diagnoses between the expert and intermediate pathologist (H&E κ = 0.78, D2‐40 κ = 0.85) and between the expert and trainee pathologist (H&E κ = 0.37, D2‐40 κ = 0.56). With the ancillary elastin staining, there was an improved agreement for VI diagnoses between the expert and intermediate pathologists (H&E κ = 0.25, elastin κ = 0.63) and between the expert and trainee pathologists (H&E κ = 0.29, elastin κ = 0.45). Conclusions: With both the ancillary D2‐40 and elastin staining there was an improved interobserver agreement for LI and VI diagnoses, regardless of the pathologist's experience. This ancillary staining may be useful in improving the accuracy of LI and VI diagnoses, helping to improve the risk stratification of early gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Lymphedema is a major complication of treatment for breast cancer. Although chemotherapy can cause lymphedema, there have been few reports about histological changes in skin and subcutaneous tissue after chemotherapy. The aim of our study was to determine whether chemotherapy affects blood and lymphatic vessels in the skin and subcutaneous fat and to investigate the relationship between these changes and extent of post-chemotherapy edema. Methods: We compared histological findings in skin and subcutaneous fat of mastectomy specimens from 38 patients who had received NAC (neoadjuvant chemotherapy) and 56 who had not (non-NAC) attending our institution from 2007 to 2016. Patients whose tumor may have affected the area examined were excluded. Blood and lymphatic vessels were identified by CD31 and D2-40, respectively. We assessed microvessel density (MVD), lymphatic microvessel density (MLVD), lumen cross-sectional area (LA), and amount of endothelium (AE) in blood and lymphatic vessels. To minimize surgical effects, we measured edema, defined as ≥ 15% thicker dorsal subcutaneous tissue than baseline, on the contralateral side. Results: MVD, LA, and AE of blood vessels were greater and MLVD not significantly different in the skin of NAC patients than in that of non-NAC patients. MVD was greater and AE of blood vessels less in subcutaneous fat of NAC patients than in that of non-NAC patients. Patients with edema had significantly less AE of blood vessels in skin than did those without it. Conclusions: These pathological findings can help to identify patients who will develop edema and improve their treatment. [ABSTRACT FROM AUTHOR]

Objective: Dermatofibroma (DF) is a benign fibrohistiocytic tumor whereas dermatofibrosarcoma protuberans (DFSP) has intermediate malignant potential. CD34 is the most commonly used antibody in differentiating these tumors. Various studies have stated the rates of D2-40 expression as 0-50% in DFSPs and 86-100% in DFs. Our aim in this study was to determine the expression of CD34 and D2-40 in DFs and DFSPs and the possible use of D2-40 in the differential diagnosis of these lesions. Material and Method: This is a retrospective study including 30 DF and 15 DFSP cases which were reevaluated for epidermal changes, the presence of a transmission zone (Grenz zone), infiltration of soft tissues, infiltration pattern and histologic subtypes in addition to cellular pleomorphism, nuclear atypia, and necrosis. A manual immunohistochemistry procedure was performed with D2-40 and CD 34 antibodies using a representative paraffin block. Results: The average age was 37.36 and 42.86 years in the DF and DFSP cases. The average diameter was 0.9 and 5.03 cm, respectively, for the DFs and DFSPs. There was a significant correlation between the two entities for sex, localization and diameter of the lesion. A significant difference was found between the positivity of CD34 and D2-40 in DFs and DFSPs. Conclusion: Additional immunohistochemical markers may be needed in DFs with CD34 positivity. Our results showed the additional helpful role of this marker in problematic cases.

Background: Milroy disease (MD) is rare and autosomal dominant resulting from mutations of the vascular endothelial growth factor receptor-3 (VEGFR-3 or FLT4), which leads to dysgenesis of the lymphatic system.Methods: Here we report a Chinese MD family with 2 affected members of two generations. We identified the mutation of c.3075G>A in one allele of FLT4 in Chinese population firstly. The father and child presented lymphedema under knees both. Unfortunately, the child was premature delivered for a car accident of the mother and then died of asphyxia. Then we gathered the tissue of the lower-limb from the child with permission from the parents and ethic committee. We stained the tissue with lymphatic marker D2-40 and hematoxylin-eosin to explore the histological changes. Afterwards, we compared the results with a normal child who unfortunately died of premature delivery also.Results: It is firstly identified the mutation of FLT4: c.3075G>A in Chinese population, and the mutation Inherited in the lineage. The histological evaluation indicated: (1) The number of lymphatic vessels decreased; (2) The morphology and structure of lymphatic vessels was abnormal. And what is added to our knowledge: (1) Capillary hyperemia and phlebectasia is severe; (2) Vascular malformations; (3) The number of vascular endothelial cells and vascular smooth muscle cells decreased; (4) Large sheets of epidermis desquamated; (5) The numbers of cutaneous appendages reduced in MD.Conclusions: Based on the new findings, we assume that mutation of FLT4 not only affect the lymphogenesis, but also the angiogenesis, and epidermis structure.

Introduction: The aims of this study were to investigate the immunohistochemical expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C), their correlation with lymphangiogenesis, angiogenesis and clinicopathological significance in human gastric cancer. Material and methods: Tissue samples of gastric cancer of 60 patients, who underwent Billroth II resection, were analyzed. The expression of COX-2 and VEGF-C proteins was calculated using a semi-quantitative immunoreactive score method. Quantitative analysis of lymphangiogenesis and angiogenesis was performed according to the method described by Weidner. Lymphangiogenesis was evaluated by immunostaining with D2-40. Angiogenesis was assessed by CD105 immunostaining. Results: There was a statistically significant difference in the mean values of COX-2 (p< 0.01) and VEGF-C (p< 0.05) between gastric cancer samples and in control samples. Angiogenesis was significantly higher in neoplastic tissue then in control group (p<0.001). Expression of COX-2 showed a significant positive linear correlation with angiogenesis (p<0.05). However, COX-2 did not correlate with VEGF-C or lymphangiogenesis. There was an association between VEGF-C and lymphangiogenesis, but without statistical significance. Lymphangiogenesis significantly correlated with lymph node metastasis (p=0.007). Expression of COX-2 showed significant correlation with type of Bormann's classification (p=0.019) and depth of invasion (p=0.03). Conclusions: The tumor cells are the major source of COX-2 and VEGF-C in gastric carcinomas. Their correlation did not show that COX-2 overexpression promotes tumor lymphangiogenesis through augmentation of VEGF-C. The results of this study suggest that neoangiogenesis is a dominant process during tumor progression, whereas lymphangiogenesis plays an important role in lymph node metastasis. [ABSTRACT FROM AUTHOR]