Inflammatory Carcinoma Research Articles

Impact of Toceranib Phosphate and Carprofen on Survival and Quality of Life in Dogs with Inflammatory Mammary Carcinomas.

Canine inflammatory mammary carcinoma (IMC) is an aggressive and rare type of mammary gland cancer in dogs where vascular endothelial growth factor and cyclooxigenase-2 overexpression usually occur, which contribute to its invasive and angiogenic nature. This study aimed to evaluate the efficacy and safety of a combined treatment regimen of toceranib phosphate and carprofen in dogs with measurable IMC. Fifteen female dogs with histopathologically confirmed IMC were included, undergoing a regimen of toceranib (2.4-2.75 mg/kg PO, three times weekly) and carprofen (4.4 mg/kg/24 h PO). Initial evaluations included physical exams, tumor measurements, complete blood count, biochemistry, urinalysis, three view thoracic radiographs, and abdominal ultrasound. Follow-up assessments of physical condition and quality of life (QOL) were conducted bi-weekly, with tumor response evaluations monthly, using RECIST v1.0 criteria. While no complete or partial responses were observed, 60% of the dogs maintained stable disease, with a median progression-free survival of 76 days and an overall survival of 90 days. Notably, 60% of the dogs showed clinical benefit through improved QOL and disease stabilization. The treatment was well-tolerated, with only grade I/II toxicities reported. Despite limited biological activity against the cancer, this protocol may enhance QOL in dogs with IMC, offering a valuable palliative option.

Cytological Features of Inflammatory Mammary Carcinoma in Dogs.

Inflammatory mammary carcinoma (IMC) is the most aggressive and malignant type of mammary carcinoma. As in humans, canine IMC resembles mastitis clinically. However, IMC is highly aggressive with high incidence of metastases and common recurrence after surgery, leading to guarded prognosis and low survival rate. Given the complex morphology of canine mammary tumours, cytological examination is not performed routinely, and IMC diagnosis relies on the association of clinical features and histopathology. The purpose of this study is to describe the characteristics of canine IMC cytology, in an attempt to find possible cytological features that allow differentiation of IMC from other mammary tumour types. We analysed preoperative cytological samples from 25 dogs with IMC, later confirmed by corroborating clinical and histopathological examinations. Distinct cytological features of canine IMC included scarce cellular cohesiveness, ballooning aspect of neoplastic cells, frequent multinucleation, irregularly dispersed and ropy chromatin pattern, and squamous metaplasia in some individualised cells or those in small groups. Our results indicate that cytological examination can contribute to the diagnosis of IMC and might help differentiate it from other mammary carcinomas, even when clinical data is not available, which is common in cytological routine.

Variability in morphology and immunohistochemistry of Crohn's disease-associated small bowel neoplasms: implications of Claudin 18 and Cadherin 17 expression for tumor-targeted immunotherapies.

Inflammatory bowel disease-associated colorectal carcinomas are known to have different morphology, immunoprofile, and genetic findings from sporadic colorectal carcinomas; however, little is known for Crohn's disease-associated small bowel neoplasms (CD-SBNs). Cadherin 17 is a useful biomarker of adenocarcinomas with intestinal phenotype and recently reported as an ideal target for chimeric antigen receptor T-cells (CAR-T) therapy for gastrointestinal carcinoma. Claudin 18 is a cell adhesion protein, and Claudin18 isoform 2 (CLDN18.2) is frequently expressed at high levels in gastric-type adenocarcinoma. Zolbetuximab, a targeted monoclonal antibody, has been developed for CLDN18.2-positive gastroesophageal adenocarcinoma. We examined a series of CD-SBNs for both Cadherin 17 and Claudin 18, and also hypothesized that expression of Claudin 18 was associated with gastric phenotype. We performed histological and immunohistochemical examinations on 25 CD-SBNs. Most of adenocarcinomas showed tubular morphology as seen in gastric carcinomas, whereas a subset of dysplasia was morphologically similar to that of the large bowel. Cadherin17 and Claudin 18 expression was identified in 93% and 57% CD-associated adenocarcinomas respectively. In Cadherin 17-positive CD-SBNs, frequent MUC5AC, MUC6, and Claudin18 expression was identified (61%, 57%, and 57%, respectively). Claudin 18-positive CD-SBNs showed significantly more MUC5AC and MUC6 expression than Claudin 18-negative CD-SBNs (P = 0.005, < 0.001 respectively). In CD-associated small bowel adenocarcinomas, Cadherin 17 expression was frequently retained and Claudin 18 was frequently co-expressed. Claudin 18 had a positive correlation with the expression of gastric mucins. These results suggest that CD-associated small bowel adenocarcinomas may be candidates for Cadherin 17- and Claudin 18-targeted immunotherapies.

Goldilocks mastectomy; a modified technique enhancing the aesthetic outcome presented as a single center single-arm prospective cohort study

BackgroundGoldilocks mastectomy represents a midway solution for breast reconstruction between flat chest and sophisticated reconstructive techniques. The literature lacks a standardization of the technique. In this study, we present a step-by-step approach with modifications in the original technique achieving better breast shape and contour within the context of standardization of the technique. MethodsA single arm prospective study was conducted at our center in which female patients with large ptotic breasts indicated for mastectomy were included. Patients with locally advanced skin changes, inflammatory carcinoma, stage IV disease as well as male patients were excluded. Recruited patients were subjected to the same surgical steps. Contralateral breast symmetrization was performed by reduction technique to patients who accepted this. All patients were requested to report their degree of satisfaction according to a simple 5-point Likert scale. Follow up mammogram was performed to all patients 1 year after the procedure. ResultsA total of 55 patients were included with a median (IQR) age of 56.0 (50.0–62.0) years. The median (IQR) BMI was 41.20 (36.55–44.35)Kg/m2. The median (IQR)operative time was 115.0 (105.0–120.0) minutes. Complications were encountered in 12 patients (21.8 %). The follow up period ranged from 19 to 66 months with a median (IQR) 36.0 (28.0–45.0)months. 98.2 % of the studied patients were either satisfied or extremely satisfied. ConclusionsGoldilocks mastectomy is a valid mastectomy option for selected patients with large ptotic breasts. Standardization of the surgical steps can help in improving the aesthetic outcome.

Single-Stage Immediate Breast Reconstruction with Acellular Dermal Matrix after Breast Cancer: Comparative Study and Evaluation of Breast Reconstruction Outcomes.

We evaluate postoperative complications, aesthetic results and satisfaction outcomes in patients with breast cancer after intervening with a skin-sparing or nipple-sparing mastectomy with an immediate prosthetic reconstruction with or without a biological mesh. Patients with multifocal breast cancer, ductal carcinoma in situ with an indication for a mastectomy and cT2 tumors with no response to primary systemic treatment were included, whereas patients aged >75 years, with inflammatory carcinoma, and severe circulatory disorders were excluded. Patients in the control group were reconstructed using a prosthesis, whereas the study group included patients reconstructed using a prosthesis and biological acellular porcine dermal mesh (Strattice™). In both groups, the result was assessed using the BREAST-Q instrument. A total of 51 patients (62 intervened breasts) were included in the study group and 38 patients (41 intervened breasts) in the control group. Implant loss and removal occurred in three patients in the study group (5.9%) and nine patients in the control group (24.3%; p = 0.030). Infections appeared in three patients in the study group (4.8%) and three patients in the control group (7.3%; p = 1.00). Skin necrosis appeared in 5 patients in the study group (12.2%) and 11 patients in the control group (21.6%; p = 0.367). Seroma appeared in five patients in the study group (12.2%) and five patients in the control group (8.1%; p = 0.514). The BREAST-Q questionnaire is a comparison between both groups regarding "satisfaction with breasts after surgery" (p = 0.026), "sexual well-being after intervention" (p = 0.010) and "satisfaction with the information received" (p = 0.049). We have noted a statistically significant decrease in implant loss in women receiving an implant with a biological mesh. A higher satisfaction was observed in patients reconstructed using Strattice™, with statistically significant differences in three items.

Electrochemotherapy for Mammary Tumour in Dogs

Background: Mammary neoplasms are the most common tumours in the bitch. Even though surgery remained the treatment of choice for mammary gland tumours except those with inflammatory carcinomas or distant metastasis; it did not seem to reduce the chances of recurrence in case of malignancy in dogs. Other alternatives to surgery are chemotherapy, immunotherapy, radiation therapy, hormonal therapy etc. The major disadvantage of chemotherapeutic agents was the lack of selectivity for tumour cells. To overcome this problem, electrochemotherapy could be used as a single or as an adjuvant therapy to surgery which could be used for treatment of inoperable tumours. Cisplatin and bleomycin are the two chemotherapeutic agents used in veterinary oncology for electrochemotherapy. This study was carried out on clinical cases of mammary tumours to study and compare the efficacies of electrochemotherapy using Cisplatin and bleomycin Methods: The research was carried out on clinical cases of canine mammary tumour presented to the Small Animal Surgical Out-Patient Unit of Madras Veterinary College Teaching Hospital for a period of one year from September 2018 to May 2021. Routine Clinical, Haematological, Biochemical and Radiographic evaluations were performed. Twelve dogs with mammary tumours, with a single solitary lump were selected for the study irrespective of the age, breed and location. Group I Cases were treated by electrotherapy with cisplastin and Group II were treated by electrotherapy with bleomycin intralesionally following which surgical excision was performed. Result: Most cases in the cisplatin group produced partial response (3/6) according to the response evaluation criteria, whereas most cases in the bleomycin group produced complete response (100% regression). Bleomycin was comparatively more efficient (1.7 times) than cisplatin in electrochemotherapy for mammary tumours. The time under anaesthesia was low which makes this procedure a suitable alternative to geriatric dogs that cannot be anaesthetised for a longer duration for surgery.

THU672 Fungating And Inflammatory Anaplastic Thyroid Carcinoma In A 64-Year Old Filipino

Abstract Disclosure: R.M. Tarrazona - Dominisac: None. M.C. Isidro: None. Background: Anaplastic Thyroid Carcinoma is a rare and lethal undifferentiated thyroid cancer that occurs in less than 2% of all thyroid malignancies. In the Philippines, this rare entity has an estimated incidence of 0.7%. Its aggressive nature is strikingly significant because it carries a poor prognosis with a median survival of 5-6 months. An exceptionally rare presentation of an Anaplastic Thyroid Carcinoma is a fungating, exophytic and inflammatory type. Case Summary: This is a case of a 64-year old female with a 2 x 2 cm erythematous patch at her anterior neck. There is progressive enlargement of the reddish neck lesion associated by burning sensation with subsequent development whitish nodules with purulent exudate. The nodules were fragile with noted bleeding on minimal manipulation. Initial impression was anterior neck cellulitis and she was given 7 days of IV antibiotics with no resolution of the lesion. Neck CT scan showed a multinodular heterogeneously enhancing mass in the left neck region measuring 6.3 x 5.2 x 5.5 cm. A core needle biopsy of the mass revealed malignant cells present: anaplastic carcinoma vs squamous cell carcinoma, with immunohistochemical stains: PAX 8 positive, p63 negative, CK 5/6 negative, BRAF negative, TTF-1 focally positive. The patient underwent tumor debulking surgery with tracheostomy. The gross specimen was sent for histopathologic examination and finally revealed Anaplastic Thyroid Carcinoma. Conclusion: The case reported was a diagnostic dilemma early during the clinical presentation due to presence of rapidly enlarging, inflammatory and fungating anterior neck mass with presence of whitish nodules with purulent exudates, bleeding and pain. She was initially treated as an abscess only to discover presence of malignancy upon further work-up. Anaplastic thyroid cancer is the most advanced and aggressive thyroid malignancy. It is very rare and the atypical fungating presentation of this ATC makes it an exceptionally rare entity. Fungating wounds are the result of cancer cells infiltrating and invading the cutaneous structure. This case report highlights the importance of harnessing a high level of clinical suspicion for anaplastic thyroid cancer even in atypical looking anterior neck mass to ensure prompt definitive diagnosis and improve overall prognosis. Presentation: Thursday, June 15, 2023

A study of antibody conjugates for the treatment of inflammatory breast cancer.

e15016 Background: Inflammatory breast cancer (inflammatory carcinoma) is a rare metastatic malignant tumor, it accounts for about 2% of all breast cancer cases. Despite its low incidence, inflammatory breast cancer is highly invasive, its five-year survival rate is less than 41%, making its prognosis the worst of all breast cancer subtypes, and effective drugs are urgently needed in clinical practice. Therefore, our study develops novel antibody conjugate drugs that can target overexpressed-ICAM-1 in inflammatory breast cancer cells as an original molecular target precisely. Methods: In this study, flow cytometry was used to perform precise and quantitative target screening of inflammatory breast cancer cell lines (SUM-149, KPL4), the endocytosis efficiency of ADC drugs was verified by flow cytometry efficiency analysis and single-photon confocal analysis, and the cytotoxicity of different drugs and cell lines was explored by CCK8 experiment. A nude mouse model of orthotopic xenograft inflammatory breast cancer was constructed, and the in vivo therapeutic effect of inflammatory breast cancer was observed by intravenous injection of two ICAM-1 antibody conjugates (ICAM-1-MMAE and ICAM-1-DXD), also the ADC drug structure with the best therapeutic effect for inflammatory breast cancer was screened. Results: ICAM-1 molecule in a variety of inflammatory breast cancer cell lines were highly over-expressed, and the antibody internalization rate was 51% at 4h, and after the peak the endocytosis efficiency slowed down into the plateau stage; ICAM1-MMAE and ICAM1-DXD are safer than first-line chemotherapy agents for breast cancer; The tumor volume was significantly reduced after administration into the orthotopic breast cancer xenograft model, which further verified the obvious effect of ADC drugs in vivo. Conclusions: Both ICAM-1-MMAE and ICAM-1-DXD have shown significant anti-inflammatory breast cancer effects in vitro and in vivo, and this study provides potential antibody conjugate drugs for targeted therapy of inflammatory breast cancer, which is expected to help improve the poor prognosis of inflammatory breast cancer.

Guidelines and Protocol of Managing Patients with Breast Problems during Pregnancy and Lactation

Most of the breast lesions found during pregnancy are benign. Pregnancy associated breast cancer (PABC) is defined as cancer that occurs during pregnancy or within 1 year of delivery. Aim of the study: To diagnose breast lesions during pregnancy, detect incidenceof masses as well as the incidence and early diagnosis of PABC. Patients and methods: 500 pregnant women (190 primigravida, 254 mutigravidaand 56 lactating) attending Kasr Al Ainy outpatient clinic having breast complaints were included in the study. Ultrasound was performed for all patients. Further investigations were performed when indicated (Mammography, MRI or core biopsy). Results: Incidence of breast mass was 25.6%. Within those cases, 5.46 had PABC. The overall incidence of PABC was 1.4%. Biopsy was performed in 13 patients (9 pregnant and 4lactating). We diagnosed 7 malignant masses (4 lactating and 3 pregnant). Pathology revealed5 invasive duct carcinoma, 1 inflammatory carcinoma and 1 adenocarcinoma. Positive family historywas found in 85.7% of malignant cases. Conclusion: Most breast masses were benign. The overall incidence of PABC was 1.4% and 5.46% within patients diagnosed with a breast mass. Obstetricians should be aware of the importance of breast examination when there is a breast complaint during pregnancy.

Tetramethylpyrazine-Rhein Derivative inhibits the migration of canine inflammatory mammary carcinoma cells by mitochondrial damage-mediated apoptosis and cadherins downregulation

BackgroundCanine inflammatory mammary carcinoma (CIMC) has a high incidence of metastasis, high lethality, and poor prognosis, which needs novel adjuvant agents. Tetramethylpyrazine-Rhein Derivative (TRD) has been shown to have antitumor activity, which is a potential research direction for CIMC. PurposeThis study evaluated the efficacy of TRD on CIMC in vitro and in vivo, and provided possibilities for the application of active compounds in traditional Chinese medicine. MethodsIn vitro, TRD cytotoxicity was measured with CCK-8. Flow cytometry and transmission electron microscope were used to detect the cell cycle, cell death, and changes in mitochondria. Wound-healing assay, cell invasion assay, and scanning electron microscope were used to evaluate the suppression of cell migration and invasion. Expression changes were detected by RT-qPCR and western blot assay. In vivo, the lung metastasis models were randomly divided into control, low-dose TRD, high-dose TRD, and positive groups. Each group was administered orally once a day for 18 days and took in vivo imaging photos. ResultsThe IC50 of TRD in CHMp and MDCK were 42.59 and 79.37 μM, respectively. TRD mediated cell apoptosis by mitochondrial damage and caused S and G2/M phase arrest by downregulating cyclin B1. Moreover, TRD reduced filopodia and inhibited cell migration by downregulating cadherins. In CIMC lung metastasis models, TRD could effectively inhibit tumor growth (P < 0.001) in the lungs without significant toxicity. ConclusionTRD showed potential activity to inhibit CIMC lung metastasis with multi-target and low toxicity.

Hallazgos por resonancia magnética de las mastitis inflamatorias de etiología desconocida

Inflammatory mastitis of unknown etiology includes the entities periductal mastitis and idiopathic granulomatous mastitis. These relatively uncommon processes usually affect women of childbearing age. They usually present as a palpable mass that is painful on palpation. These lesions have an insidious clinical course and are difficult to diagnose. In some cases, they can resemble malignant disease, especially in some very developed cases where they can resemble inflammatory carcinoma. When considered all together in the appropriate clinical context, the magnetic resonance imaging signs enable us to approach a specific diagnosis. These entities share clinical and radiological characteristics with malignant processes, so biopsies are fundamental to rule out malignancy.

Papanicolaou Smear screening in Aligarh: A Review of the Cases

ABSTRACT: Cervical cancer is the second most common cancer after breast cancer. The risk factors associated with this dreaded yet preventable cancer is age at sexual debut, parity, multiple sexual partners, use of contraceptives and smoking etc. Fortunately, the cervical cancer are preventable because of the early detection of precancerous lesions. This is made possible by the screening procedures routinely in practice such as Pap smear, visual inspection and HPV. Methodology: The study was conducted to evaluate cervical cytological abnormalities, through pap smear reported as inflammatory lesions, precancerous (CIN1/ CIN2/CIN3) and carcinoma in situ, in women who underwent pap smear screening at the hospital. Discussion and Conclusion: This was a prospective study of pap smears received in the cytopathology laboratory from January 2019 to July 2019. A total of 202 Papanicolaou smears were sent to the cytology laboratory during the 6month time period. There were 112 (55.4%) abnormal pap smears (epithelial cell abnormalities, infections and inflammatory smears). 14 (6.9%) smears were inadequate or unsatisfactory for evaluation. 89 (44%) cases had inflammatory changes whereas epithelial abnormality was seen in 23 (11%). These findings corroborate with the fact that Papanicolaou (Pap) test is an important screening tool and is a simple technique to detect precancerous cervical lesions.

Evaluation of tumour associated macrophages in different histopathological types and grades of canine mammary tumours

Canine mammary tumours (CMTs) are the second highest reported tumours in female dogs, following skin tumours. Human breast cancers (HBCs) and CMTs share common clinical and molecular features and hence, CMTs are considered as ideal models to study the different aspects of HBC. The study utilised samples from 25 CMT suspected cases presented to University Veterinary Hospitals in Thrissur district from December 2020 to October 2021. The tumour samples were analysed histopathologically and the lesions were classified. Among the 25 cases, one was identified as ductal hyperplasia, one as a benign myxoma and all the others were found to be malignant neoplasms. Malignant tumours were further categorised into different histotypes.Histological Malignancy Grading (HMG) was also done in 23 malignant CMTs and 21.74 percent were found to be of grade I, 47.83 per cent were grade II and 30.43 per cent were grade III. Majority of the malignant tumours were simple carcinomas which comprised tubulopapillary, ductal, cribriform, solid and comedocarcinomas. Highly aggressive tumours like cribriform, solid, comedo and inflammatory carcinomas belonged to higher grades, either II or III. Infiltration of tumour associated macrophages (TAMs) was studied in different histotypes and grades of CMTs. It was identified that malignant high grade CMTs had greater TAM infiltration and hence, with further validation TAMs could be effectively used in predicting prognosis and also as a therapeutic target.

Enterocolic phlebitis: a rare cause of bowel ischemia and review of the literature.

Enterocolic phlebitis (EP) is a rare cause of bowel ischemia due to isolated venulitis of the bowel wall and mesentery without arterial involvement. EP is often misdiagnosed as inflammatory bowel disease, carcinoma, or diverticulitis due to non-specific symptoms as well as non-specific clinical and radiological findings. While unresponsive to pharmacotherapy, surgical resection of the affected bowel appears to be the only successful therapy with a very low recurrence rate. Etiology of EP remains unknown. We report a case of EP with rare presentation in the left hemicolon and unusual histological findings emphasizing the heterogeneity of this cause of enterocolic ischemia. The review and comparison of the three entities-EP, mesenteric inflammatory veno-occlusive disease (MIVOD), and idiopathic myointimal hyperplasia of mesenteric veins (IMHMV), all describing patterns of bowel ischemia due to isolated pathology of mesenteric veins-reveal that the current terminology is unclear. EP and MIVOD are very similar and may be considered the same disease. IMHMV, though, differs in localization, symptom duration, and histological findings but also shares features with EP and MIVOD. Further studies and harmonized terminology are inevitable for better understanding of the disease, prevention of unnecessary pharmacotherapy, and reduction in time to diagnosis.

Breast cancer and prevention perspectives: A public health challenge, Buea regional hospital, Cameroon

With 2.100.000 cases annually, breast cancer (BC) is the most common gynecological cancer globally; 627.000 of those cases result in death yearly. In the next 20 years, it is anticipated that there will be 14.000.000 cases annually and 8.200.000 fatalities. There are numerous histological subtypes of BC. The various cancers include invasive ductal carcinoma, papilloma, medullary carcinoma, phyllode tumors, ductal carcinoma in situ, lobular carcinoma in situ, and Paget disease. BC is a huge public health concern because of the steadily rising cases in our low-resource environments, thus raising the stakes to develop effective screening and early detection programs to reduce morbidity and mortality. Breast ultrasonography and clinical examination appear to hold promise for screening campaigns. Methodology: On the one hand, a descriptive retrospective analysis was conducted based on the pathology laboratory registry of the regional hospital in Buea, Cameroon. The time frame was from March 4, 2016, through May 25, 2019. On the other hand, we appreciate the rising number of women who attended BC screening programs from 2020 to 2022. BC was screened via clinical breast examination and breast ultrasonography before biopsy for confirmation. Results: In terms of frequency, the following precancerous lesions and cancers were recorded: invasive breast carcinoma, carcinoma in situ, papilloma, inflammatory carcinoma, phyllode tumours, and angiosarcoma. Their respective percentages were; 74.84, 14, 47, 6.92, 1.89, 1.57, and 0.32. The number of women who came for BC screening increased steadily from 123 in 2020 to 266 in 2021 and 552 in 2022. All with positive biopsy results first underwent a clinical examination. In the presence of any suspicious signs, an ultrasound investigation was ordered. A biopsy was requested in case of any image suspicious of BC. Response to the cancer screening campaigns in Buea has increased markedly since the project's initiation. Conclusion: Breast cancer is a heterogeneous malignancy made of various histological types. Our study identified the following pathologies in order of frequency: invasive breast carcinoma, ductal carcinoma in situ, papilloma, inflammatory carcinoma, phyllode tumours, and angiosarcoma. As awareness grows as years go by, there is a huge public health challenge. For mass screening, Clinical examination of the breasts and breast ultrasound seems to be the way forward in prevention, as recommended by many clinical trials and WHO. Objectives: The study aimed to determine the frequency of various types of breast cancer and find a good grassroots approach to BC screening in low-resource settings like ours.

Idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis mainly affects women of childbearing age, mostly several months to years after breastfeeding. The etiopathogenesis is unknown to this day. Because clinical manifestations can mimic infectious mastitis or inflammatory carcinoma, the dia-gnostic process is often prolonged. The correct dia-gnosis is determined only on the basis of histopathological findings. To this day, there is no uniform consensus on the treatment of idiopathic granulomatous mastitis. The chronic nature of the disease as well as the tendency to recurrences despite the benign nature of the disease affects the quality of life of patients. Case reports from the Gynecoly and Obstetrics Clinic in University Hospital in Tren&#269;ín also point to an adverse effect on womens lives.

The C1q-ApoE complex: A new hallmark pathology of viral hepatitis and nonalcoholic fatty liver disease.

We recently identified a high-affinity C1q-ApoE complex in human artery atherosclerotic intima lesions and in human amyloid plaques of Alzheimer’s Disease brains defining a common pathogenetic pathway of two diverse diseases, i.e. atherosclerosis and dementia. C1q is the initiating and controlling protein of the classical complement cascade (CCC), which occupies a key role in multiple acute and chronic inflammatory tissue responses. C1q is largely produced by myeloid cells including Kupffer cells (KCs) and subsequently secreted into the circulation as an inactive preprotein. Its binding partner, Apolipoprotein E (ApoE), is produced by KCs and hepatocytes and it is also secreted into the circulation, where it regulates essential steps of lipid transport. In addition to its major source, ApoE can be produced by non-liver cells including immune cells and multiple other cells depending on local tissue contexts. To initiate the CCC cascade, C1q must be activated by molecules as varied as oxidized lipids, amyloid fibrils, and immune complexes. However, ApoE is mute towards inactive C1q but binds at high-affinity to its activated form. Specifically, our studies revealed that ApoE is a CCC-specific checkpoint inhibitor via the formation of the C1q-ApoE complex. We proposed that it may arise in multiple if not all CCC-associated diseases and that its presence indicates ongoing CCC activity. Here, we turned to the liver to examine C1q-ApoE complexes in human B- and C-viral hepatitis and nonalcoholic fatty liver disease (NAFLD). In addition, we used multidrug-resistance-2 gene-knockout (Mdr2-KO) mice as a model for inflammatory liver disease and hepatocellular carcinoma (HCC) pathogenesis. In normal murine and human livers, KCs were the major C1q-producing cell type while hepatocytes were the primary ApoE-forming cell type though the C1q-ApoE complex was rare or nonexistent. However, significant numbers of C1q-ApoE complexes formed in both Mdr2-KO, human viral hepatitis, and NAFLD around portal triads where immune cells had infiltrated the liver. Additionally, high numbers of C1q-ApoE complexes emerged in human livers in areas of extracellular lipid droplets across the entire liver parenchyma in NAFLD-affected patients. Thus, the C1q-ApoE complex is a new pathological hallmark of viral hepatitis B and C and NAFLD.

A BCC masquerading as a fungating breast mass

A 55-year-old female presented with a growth on her left chest that was increasing in size. The growth had been present for several years. The patient had no complaints of pain; just concerns about the presence of the mass. Upon examination, the patient had a polypoid, lobulated, violaceous, and red fungating mask measuring approx. 7.0 cm x 6.0 cm (Fig. 1a). Malignant breast disease encompasses many histologic types that include, ductal or lobular carcinoma, infiltrating ductal or lobular carcinoma, and inflammatory carcinoma. Benign masses can include fibroadenoma, intraductal papilloma, and abscess. Patient was referred to a general surgeon for removal due to the uncertain nature of this growth (Fig. 1b). Pathology was positive for a basal cell carcinoma with focal squamous cell differentiation, nodular type (Fig. 2). All resected margins were negative. Recovery was uneventful. Basal cell carcinomas located on the trunk account for only 10 percent of all cases. The majority are in sun exposed areas such as the face and neck [1,2].

Establishment of stable expression of firefly luciferase and EGFP in a canine inflammatory mammary carcinoma cell line and tumor-bearing model in nude mice.

Canine inflammatory mammary carcinoma (CIMC) is a type of canine malignant mammary tumor with a poor prognosis and high mortality. We transduced firefly luciferase and enhanced green fluorescent protein (EGFP) into CHMp, a CIMC cell line, and established CHMp-Luc-EGFP cells. We investigated the characteristics of this cell line in vitro and in vivo. CHMp-Luc-EGFP was passaged continuously 75 times, with stable expression of luciferase and EGFP. Compared with the wild-type, CHMp-Luc-EGFP had similar proliferation, metastasis, histopathology characteristics, and expression of E-cadherin, N-cadherin, and Ki-67. A tumor-bearing model was established by implantation of CHMp-Luc-EGFP cells, and the dynamic changes of tumors were visualized and quantified using the IVIS imaging system. In summary, the cell line we established could reflect the biological characteristics of CHMp cells, visualize the tumor progression in vivo, and provide a powerful tool for the study of CIMC.

Case Report : Lymphocytic Lobulitis With Fibrocystic Disease Of The Breast

Lymphocytic lobulitis , is a fibroinflammatory benign condition of the breast which is associated with type 1 diabetes mellitus. This benign condition is uncommon and may be mistaken for inflammatory carcinoma of the breast. We report the case of a 61 year old female patient who presented with a lump in the right breast with a history of Type 2 diabetes mellitus. The lump was associated with discharge and recent onset pain. On examination a vague lump which was non mobile, involving the right breast was palpable. A single firm mobile right axillary lymph node was palpable. Peau d’orange or orange peel appearance which occurs due to blockage of sub dermal lymphatics by tumour infiltrates, was noted over the skin. Clinically the features were suggestive of inflammatory carcinoma. Mammogram suggested an inflammatory carcinoma. Ultrasound of the breast was suggestive of right duct ectasia and diffusely thickened breast with a Breast Imaging Radiology and Data System (BIRADS) score of 3. An incision biopsy was performed with histopathology confirming the lesion as lymphocytic lobulitis with fibrocystic breast disease. The patient was symptomatically managed with analgesics and reassured. She was observed on regular follow up and is currently healthy. Lymphocytic lobulitis is a rare benign lesion which mimics carcinoma. Clinically it presents with ill defined single or multiple breast lumps in young or middle aged women with thickening and hardening of skin. Magnetic Resonance Imaging better differentiates this otherwise indolent lesion from malignancies. A histopathological examination is usually confirmatory and required to alleviate concerns of patients regarding presence of a malignancy which has a much fearsome physical and psychological implication.&#x0D;