Hepatoid Gland Research Articles

Calprotectin and β-Catenin Expression in Canine Hepatoid Gland Tumors and Correlation with Macrophage Infiltration

β-catenin is deregulated in cancer malignancies and drives the epithelial-to-mesenchymal transition (EMT). Calprotectin plays antioxidant activities, modulates inflammation and immune responses, and influences cell migration and invasion. Calprotectin can contribute to the progression of various types of cancer. Macrophages expressing calprotectin (MAC387) have been related to M1 polarization and promote EMT. In this study, β-catenin and calprotectin expression in canine hepatoid gland tumors and its relationship with MAC387-positive macrophages is reported. Β-catenin was membranous and strong in hyperplasia and adenomas, moderate or weak in well-differentiated carcinomas, and absent in less-well-differentiated carcinomas. In cells with squamous differentiation, β-catenin was weak or absent. In benign and malignant lesions, MAC/387 positivity was found in both macrophages and clusters of cells with squamous differentiation arranged in whorls centered on ductal-like spaces. These clusters were more voluminous in carcinomas, sometimes with a center of lamellar keratin (horny pearls) and were surrounded by neoplastic hepatoid cells variably positive to calprotectin. The number of calprotectin-positive macrophages progressively increased in the stroma of carcinomas. These findings suggest that hepatoid glands are a useful model for studying the different roles of β-catenin and calprotectin in the tumor milieu and their involvement in tumor differentiation and EMT.

First study on the immunohistochemical expression of cyclooxygenase-2 and clinicopathological association in canine hepatoid gland neoplasms.

Hepatoid gland neoplasms (HGNs) constitute one of the most common cutaneous tumors that arise from perianal glands in dogs and are clinically characterized by rapid growth. Cyclooxygenase-2 (COX-2), the inducible form of the enzyme, is associated with several hallmarks of tumorigenesis. Its expression has been confirmed in several human and animal neoplastic tissues, but there are no reports in hepatoid gland tissues. Therefore, this study aimed to investigate COX-2 immunoexpression in canine HGNs, compare the expression among groups of normal hepatoid glands, hepatoid gland adenomas (HGAs), hepatoid gland epitheliomas (HGEs), and hepatoid gland carcinomas (HGCs), and assess the association of the COX-2 expression with clinicopathological features. Sixty-one formalin-fixed paraffin-embedded canine hepatoid gland tissues (20 samples of HGAs, 16 of HGEs, 15 of HGCs, and 10 of normal hepatoid glands) were analyzed for COX-2 expression using immunohistochemistry with scoring for percentage positivity and intensity. Multiple comparisons of COX-2 expression among normal and neoplastic hepatoid glands and the associations between COX-2 expression and clinicopathological features were analyzed. Cyclooxygenase-2 expression was not detected in 60% of normal hepatoid glands and 25% of HGAs. Seventy-five percent of HGAs had a weak expression, while 43.7% and 56.3% of HGEs showed weak and moderate expression, respectively. The expression of HGCs ranged from weak (13.3%) to moderate (33.3%) and strong (53.3%). The immunoreactivity score of COX-2 labeling was significantly different among the normal and neoplastic hepatoid glands (p < 0.0001). The highest score was observed in the HGCs. Only in HGCs, the strong COX-2 expression was significantly associated with some clinicopathological features, including tissue invasion (p = 0.007) and necrosis (p = 0.029). These results suggest that COX-2 may play a role in the modulation of neoplastic cell growth. These preliminary data lead to further investigation on the potential of COX-2 expression as a prognostic indicator and COX-2 inhibitors for canine HGCs treatment.

Benign Mixed Mammary Tumour with Hepatoid Gland Differentiation in a Dog

A 10-year-old spayed female Shih Tzu underwent surgery to remove a tumour (8mm diameter) in the right 4th mammary gland. Histopathologically, the tumour consisted of four different components: luminal epithelial cells, myoepithelial cells, cartilage and well-differentiated hepatoid gland-like cells. There were multiple nests composed predominantly of hepatoid gland-like tissue with a small number of tubules formed by luminal epithelial cells at the periphery, in which continuity between the two components was seen. Immunolabelling for cytokeratins (CK14, CK18 and CK19), p63 and α-smooth muscle actin clearly distinguished the neoplastic luminal epithelial, myoepithelial and hepatoid gland-like cells. The immunohistochemical phenotype of the hepatoid gland-like neoplastic cells was identical to that of normal hepatoid gland cells. Based on these findings, a diagnosis of benign mixed tumour of the mammary gland with differentiated hepatoid gland cells was made. To our knowledge, this is the first report of a canine mammary tumour with hepatoid gland differentiation.

Interobserver variability in the diagnosis of canine hepatoid gland tumors

The reported prevalence of canine hepatoid gland tumor (HGT) varies widelyowing mainly to the lack of well-defined diagnostic criteria and poor interobserver agreement. The aim of the present study was to improve the level of diagnostic agreement among pathologists in canine HGT. Five pathologists diagnosed and classified morphological features in 57 cases of canine HGT and, based on their reports, diagnostic algorithms were devised using recursive partitioning analysis. The proportion of diagnoses of malignant hepatoid neoplasia among the five pathologists ranged from 26.3 to 50.9%. Interobserver diagnostic agreement was classified as fair (κ=0.54) but improved to good (κ~0.65) following application of two novel diagnostic algorithms based on histomorphological features as sebaceous differentiation, mitotic count, atypical mitosis and cellular atypia. This study has demonstrated that interobserver agreement in the diagnosis of canine HGT could be improved using novel algorithms. Further analyses are warranted to validate the proposed classification systems applying a higher sampling of canine HGTs.

The High Expression of Legumain in Canine Neoplasms: A Retrospective Analysis of 100 Cases.

Simple SummaryCancer is the leading cause of death in humans and is one of the most common canine diseases. The similarities in pathological features and tumor behaviors between spontaneous canine tumors and their human counterparts make dogs ideal models for comparative cancer research. Legumain is a novel asparaginyl endopeptidase that is overexpressed in numerous types of human tumors. Furthermore, legumain-targeted cancer therapy has been proposed, and the treatment efficacy is well-tolerated. Previous studies have shown that legumain regulates extracellular matrix degradation and triggers the invasion and the metastasis of tumors. However, in dogs, the role of legumain in the progression of tumors remains largely unknown, and few investigations have described the expression levels of this protein in canine tumors. The present study was carried out to evaluate whether legumain is expressed in ten different types of canine neoplasms. We found that heightened signals of legumain were expressed in all canine tumor samples in the study, and, notably, the non-mesenchymal types of tumors harbored relatively high expression levels. This study is the first to describe the legumain distribution pattern in a series of canine tumors. Though further investigation is needed, the current study has provided large-scale pan-screening data on legumain as a potential biomarker, or a therapeutic target, in veterinary oncology.Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively (p < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study.

Histopathological study of canine hepatoid gland tumours

Hepatoid gland neoplasms arise due to disorganized and uncontrolled proliferation of cells of hepatoid glands. These are the modified sebaceous glands located mainly in the perianal area. Gross and histological findings of canine hepatoid gland tumours were evaluated. Dogs of different breed, age and sex that were presented to Department of Veterinary Surgery and Radiology, College of Veterinary and Animal Sciences, Mannuthy formed the materials for the present study. Grossly, tumours were solitary or multiple irregular shaped intradermal masses. The excisional biopsy samples were collected in 10 per cent neutral buffered formalin after surgical removal of tumour mass. Histopathologically, the masses were encircled by fibrovascular capsule which extended to the parenchyma as tumour stroma, which separated it into lobules. Two cases of hepatoid gland adenoma one case of hepatoid gland epithelioma and two cases of carcinoma were recognised on histopathological examination. Hepatoid adenoma were characterised by proliferation of hepatocyte like hepatoid gland epithelial cells with extensive sebaceous differentiation and were arranged in cords and anastomosing trabeculae. In hepatoid gland epithelioma, many of the cells were basaloid reserve cells with fewer hepatocyte like cells. Histopathological examination of carcinoma revealed irregular arrangement of the hepatoid cells which showed varying degrees of maturation and marked nuclear pleomorphism. The malignant hepatoid cells had abundant eosinophilic cytoplasm and large nuclei with several prominent nucleoli and mitotic figures.

Neoplasms in domestic hamsters in Southern Brazil: epidemiological and pathological aspects of 40 cases1

ABSTRACT: Although neoplasms are commonly reported in domestic hamsters, retrospective studies approaching spontaneous tumors with data regarding epidemiological findings are scarce. The present study aimed to describe the epidemiological and pathological findings of 40 cases of tumors in domestic hamsters diagnosed in a veterinary pathology laboratory in Southern Brazil from 2002 to 2019. Chinese hamster (Cricetulus griseus) was the most commonly affected species (16/40), followed by Djungarian hamster (Phodopus sungorus, 11/40) and Syrian hamster (Mesocricetus auratus, 4/40). Among the cases, 57.5% were females (23/40), while 42.5% were males (17/40). The affected hamsters’ median age was of 14-months old, with an age range of 8- to 36-months old. Twenty-four cases were assessed as anatomopathological samples (biopsies), while 16 were composed of carcasses submitted to postmortem examination, and, therefore, the neoplasm was related to the cause of death. The integumentary system was frequently affected (60%, 24/40), followed by the female reproductive tract (22.5%, 9/40), hematopoietic system (10%, 4/40), digestive tract (5%, 2/40), and endocrine system (2.5%, 1/40). The most frequent neoplasm was squamous cell carcinoma (35%, 14/40), mostly on the lip/nasal region (50%, 7/14). Other tumors included fibrosarcoma (10%, 4/40), lymphoma (10%, 4/40), mammary cystadenoma (10%, 4/40), apocrine sweat gland adenoma (7.5%, 3/40), hemangiosarcoma (5%, 2/40), leiomyosarcoma (5%, 2/40), and granulosa ovarian cell tumor (5%, 2/40). The five remaining cases occurred individually and were composed of hepatoid gland adenoma, solid thyroid carcinoma, cutaneous melanoma, ovarian teratoma, and cutaneous trichoblastoma. Neoplasms were identified as an important cause of death and major reason to perform biopsy in domestic hamsters in Southern Brazil.

Metastatic Carcinoma with Hepatoid Gland Differentiation in a Grey Wolf (Canis lupus)

Metastatic Carcinoma with Hepatoid Gland Differentiation in a Grey Wolf (Canis lupus)

Cytological differentiation between benign and malignant perianal gland proliferative lesions in dogs: a preliminary study.

To evaluate the diagnostic utility of individual cytological criteria and their best combination to differentiate benign from malignant perianal gland proliferative lesions in dogs. Retrospective study of cytological samples of canine perianal gland proliferative lesions that had subsequent histopathological confirmation. Seventy-seven perianal gland nodules from 56 dogs were included. Histologically, lesions were diagnosed as hyperplasia (n=2), adenoma (n=53), epithelioma (n=6) and carcinoma (n=16). Of the 28 cytological criteria assessed, 13 showed promise for distinguishing benign from malignant lesions. A diagnostic algorithm with an 87% accuracy (sensitivity, 90.9%; specificity, 85.4%) was developed from these data. Cytological evaluation can provide useful information for presurgical differentiation between benign and malignant hepatoid gland proliferative lesions. The proposed algorithm must be validated and tested for reproducibility in further, preferably larger, series of cases.

CYTOKERATIN PROFILES OF CANINE ANAL SAC AND HEPATOID GLAND NEOPLASMS

Ten adenocarcinomas of the apocrine gland of the anal sac and 11 hepatoid gland neoplasms were studied to determine the coordinate expression of cytokeratin 7 (CK7) and cytokeratin 14 (CK14) using commercially available antibodies. Hepatoid gland neoplasms included hepatoid gland adenomas, carcinomas and a single epithelioma. All 10 (100%) adenocarcinomas of the apocrine gland of the anal sac had CK7[Formula: see text]/CK14[Formula: see text] immunophenotype, whereas all 11 (100%) of hepatoid neoplasms expressed CK7[Formula: see text]/CK14[Formula: see text] immunophenotype. Hepatoid gland adenomas, carcinomas, and epithelioma could not be differentiated based on the cytokeratin immunophenotype. Hepatoid gland neoplasms could be differentiated from adenocarcinomas of the apocrine gland of the anal sac by differences in the CK7/CK14 immunophenotypes with a [Formula: see text]-[Formula: see text]. The results of this study provide further support for the use of coordinate expression of CK7/CK14 to differentiate apocrine gland adenocarcinomas of the anal sac (CK7[Formula: see text]/CK14[Formula: see text]) from hepatoid gland neoplasms (CK7[Formula: see text]/CK14[Formula: see text]).

EGF Level in Hepatoid Gland Adenomas and Hepatoid Gland Epitheliomas in Dogs After Administering Tamoxifen.

Neoplastic lesions of perianal glands account for approximately 10% of all skin cancer cases in dogs. They occur in many dog breeds, usually in male animals aged over 6 years. Due to their hormone-dependency, tamoxifen can be used in antineoplastic treatment. The aim of the study was to measure epidermal growth factor (EGF) levels in the serum of dogs with perianal tumours after tamoxifen treatment and to use it as a prognostic factor for further treatment. The study was performed on 19 male dogs aged between 6 and 14 years, diagnosed with neoplastic hyperplasia in the perianal region. The control group comprised 10 healthy dogs brought in for routine castration. The research material comprised blood drawn from the animals and tumour specimens for histopathology. The study group received 1-month treatment with tamoxifen. Blood serum was then tested for 17-β oestradiol level, and for EGF level on the first day of the therapy and 6 months after treatment completion. Hepatoid gland adenomas were diagnosed in 10 cases, and hepatoid gland epitheliomas in nine cases. Elevated 17-β oestradiol levels were observed in all dogs. On the first day of treatment with tamoxifen, the serum EGF levels in all study groups were higher than in the control group. At the 6-month follow-up, the EGF levels were significantly reduced in hepatoid gland adenoma cases compared to those taken on the first day of treatment of tamoxifen, while in animals with hepatoid gland epithelioma, it was greatly increased and was correlated with relapse. Perianal gland tumours are characterised by EGF overexpression, which can be helpful in early-stage prognosis and treatment. An increase in EGF levels 6 months after tamoxifen therapy correlates with disease progression and may be a useful prognostic factor.

Clinical studies on anal tumors in dogs

The anal and perianal region contains multiple structure and glands, some of which are unique to the area. Anal sacs or perianal sinuses are paired, lateral, cutaneous, anal diverticula lined by a cornified, stratified squamous epithelium. Dogs have apocrine tubular anal sac glands that open into the anal sacs. Perianal glands are modified sebaceous glands, they are referred as hepatoid glands, because of their histologic resemblance to hepatocytes. Incidence,symptoms and surgical and medical management of anal tumors was studied.

Fine needle aspiration cytology (FNAC) in the diagnosis of canine hepatoid gland tumors- A comparative study with histopathology

Bu calismada hepatoid bez tumorlerinin sitolojik ve histopatolojik bulgulari karsilastirilarak sitolojik taninin guvenirligi arastirildi. Bu amacla hepatoid bez tumoru suphesi bulunan 32 farkli irk, yas ve cins kopekten alinan ornekler kullanildi. Sitolojik ornekler Ince Igne Aspirasyon Sitolojisi (IIAS) teknigine gore alindi, havada kurutularak May-Grunwald Giemsa (MGG) ile boyandi. Histopatolojik inceleme amaciyla alinan dokular ise %10’luk notral formalin solusyonunda tespit edilerek rutin doku takibine alinarak hematoksilen eozin (HE) ile boyandi. Calisma sonucunda; 32 ornegin %84.37’sinde sitolojik ve histopatolojik taninin ortustugu, buna karsilik 5 olguda hatali taniya gidildigi goruldu. Sitolojik olarak yapilan incelemelerde 27 ornegin 18 (%66,7)’ ine adenom, 6 (%22,2)’ine karsinom ve 3 (%11,1)’une benign-epitelyom tanisi konuldu. Histopatolojik olarak ise 32 olgunun 22 (%68,7)’u hepatoid gland adenom (HGA), 7 (%21,9)’i hepatoid gland karsinom (HGK) ve 3 (%9,4) hepatoid gland epitelyom (HGE) olarak tespit edildi. Sonuc olarak kopeklerde hepatoid tumorlerde IIAS teknigi ve sitolojik taninin erken tanida yararli olabilecegi kanisina varildi

Frecuencia Histopatológica de Neoplasias Perianales en Caninos: Casuística del Laboratorio de Patología Veterinaria de la Universidad Nacional Mayor de San Marcos (2005-2012

&lt;p&gt;El objetivo del presente estudio fue determinar la frecuencia de neoplasias perianales en caninos mediante diagnóstico histopatológico en el Laboratorio de Patología Animal de la Universidad Nacional Mayor de San Marcos, Lima, Perú, en el periodo 2005-2012. Se diagnosticaron 52 casos de neoplasias perianales dentro de 1283 casos de neoplasias caninas (4.1%). El adenoma de glándulas hepatoides fue el de mayor frecuencia (46.2%, 24/52).&lt;/p&gt;

Coordinate expression of cytokeratins 7 and 14, vimentin, and Bcl-2 in canine cutaneous epithelial tumors and cysts.

Forty-seven canine cutaneous epithelial tumors and cysts were examined to determine coordinate expression of cytokeratins 7 (CK7) and 14 (CK14), vimentin, and Bcl-2 using commercially available antibodies. Within non-affected normal skin adjacent to tumors or cysts, CK7 expression was observed in luminal cells in apocrine glands; CK14 expression was observed in the stratum basale, stratum spinosum, stratum granulosum, basal layer of outer root sheath, sebaceous glands, and myoepithelial cells of apocrine glands; vimentin expression was observed in dermal papilla and scattered non-epithelial cells within the epidermis; and Bcl-2 expression was observed in scattered non-epithelial cells in the epidermis and some apocrine glands. The pattern of expression of CK7 and CK14 in cases of adenocarcinoma of the apocrine gland of the anal sac (CK7+/CK14-) and hepatoid gland tumors (CK7-/CK14+) may prove useful for diagnostic purposes. Loss of expression of CK14 and vimentin, identifying myoepithelial cells, was observed in apocrine and ceruminous adenocarcinomas. Differences in patterns of expression of Bcl-2 were observed between infundibular keratinizing acanthomas compared to trichoepitheliomas.

Perianal gland adenocarcinoma with metastases in dog: A case report

Canine perianal adenocarcinoma is a malignant tumourthat occurs mainly in old dogs and arises from the modified sebaceous perianal glands, often referred to as “hepatoid glands” because of their morphological resemblance to hepatocytes. The present communication reports a perianal gland carcinoma with metastases to various organs. ALabrador bitch was presented for postmortem examination with the history thatthe animal being euthanized as it was seriously ill and not responding to any therapy. Grossly, the perianal gland was enlarged and bulging and covered by intact skin. Large tumour mass about 400g and firm in consistency was observed in the perianal region, but covered by skin. The retroperitoneal and iliac lymph nodes, liver, lungs and their associated lymph nodes also showed metastatic nodular tumour masses. Histologically, the tumor consisted of single cell type undifferentiated reserve cells with hyper chromatic nuclei, prominent nucleoli, little cytoplasm and revealed a few mitotic figures. These cells were closely packed with little interstitial connective tissue. The necrosis was also noticed at the centre of the each lobule. Peripherally, there was infiltration of inflammatory cells and focal haemorrhages. Similar type of undifferentiated reserve cells was observed as solid pattern in the lungs and lymph nodes. A rare unusually enlarged perianal gland carcinoma with metastases in lung, liver and lymph nodes has been described.

Concurrent metastatic hepatoid gland carcinoma and eosophagogastric leiomyosarcoma in a dog

A 17-year-old male, mongrel dog was evaluated for a primary mass localized between perianal and sacral region and metastatic foci on lung. It was also encountered coincidentally with another mass taking place between distal esophagus and cardia of stomach and metastatic foci in kidney. In histopathological examination, perianal localization of mass and metastatic foci on lung were diagnosed as hepatoid gland carcinoma while esophagogastric mass and metastatic foci in kidney were diagnosed as leiomyosarcoma. In immunohistochemical examination, Ki-67 marker gave positive reaction in nuclei of anaplastic hepatoid gland cells in spite of vimentin and α-smooth actin positivity were found in reserve cells of the tumor. But, there was only positive with actin marker in leiomyosarcoma. It is considered useful to share results of the two different concurrent tumor in same dog

An overall assessment of circumanal gland adenoma in a terrier mix breed dog

In September 2012, a 10-year-old, intact male, terrier mix breed dog was evaluated because of multiple, 0.5 to 1.2 cm in diameter, round, intradermal nodules around the anus. It had surgery to excise a firm, painful swelling in the left ventrolateral perianal region and the excision part was observed under light microscopy. The mass spreading in to sub acute was of left hind leg out from the ventro-lateral of anus, 1.2 cm×1 cm/0 cm×0.5 cm in size and 125 g in weight. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Significant laboratory data demonstrated microcytic anemia (hemoglobin of 6.4 mg/dL) and normal coagulation times. No remarkable abnormalities were found in the complete blood count and an ionized calcium of 1.91 mmol/L (reference range, 1.1-1.3 mmol/L) was confirmed hypercalcemia. On cytologic and histopathologic examinations, evaluation of the aspirate revealed a prominent population of round-to-polygonal nucleated cells arranged as cohesive groups with isolated individual cells. A mild degree of anisocytosis and anisokaryosis was observed. In addition, smaller reserve type cells, with darker cytoplasm and a higher nucleocytoplasmic ratio. The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations, the well-developed stroma surrounding the lobules and hepatoid cells was noted. Ulceration, hemorrhage, necrosis and secondary infection with inflammatory cell infiltrates are common. These cytology and histopathology features are consistent with hepatoid gland adenoma.

The morphogenesis of mammalian cutaneous glands in evolutionary perspective

The morphogenesis of mammalian cutaneous glands is considered based on the analysis of the literature and our own original data with the focus on the issues of gland polymorphism and specific features in postnatal development (from the case study of circumanal hepatoid glands of newborn domestic dogs), including the features reflecting the evolutionary relationships of various types of cutaneous glands. The hepatoid glands are a component of the glandular complex ofthe hair follicle, which also includes sebaceous and sweat glands; have a specific structure; and produce protein secretion by a merocrine pathway. Characteristic of these glands are wide polymorphism, sex- and age-related differences in the degree of development, occurrence in only a few phylogenetically related mammalian taxa (even-toed ungulates and carnivores); and a signaling type of their secretion. The data support the "generative concept," relying on the idea of a separate and independent origination of diverse derivatives of the external integuments.

New p53 mutations in canine skin tumours

TUMOURS of the skin and subcutaneous tissue are the most common tumours affecting dogs; they represent about 35.4 to 46.5 per cent of all tumours diagnosed in this species (Gamlem...