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A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small,...
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... ultrasonographical and radiographical examinations detected no tumours or masses in the thoracic or abdominal cavities. Additional radiation and chemotherapy was not performed after the surgi- cal excision. The dog died of malignant islet cell tumour and systemic metastases with hypoglycaemia and anaemia 19 months after excision of the mammary tumour. At necropsy examination, the tumour diagnosed at the time of biopsy collection was not observed in other organs, including the mammary glands. The original mammary mass and inguinal lymph node were fixed in 10% neutral-buffered formalin and embedded in paraffin wax. Sections (3 m m) were stained with haematoxylin and eosin (HE), mucicarmine, periodic acid e Schiff (PAS) and Grimelius stains. Serial sections were subjected to immunohisto- chemistry (IHC) using a streptavidin e biotin complex method with primary mouse antibodies specific for cytokeratin (CK) AE1/AE3 (Dako, Glostrup, Denmark; 1 in 200 dilution), low molecular weight CK (CAM5.2; Becton Dickinson, Franklin Lakes, New Jersey, USA; prediluted), CK8 (Progen Biotechnik GmbH, Heidelberg, Germany; 1 in 50 dilution), CK20 (Dako; 1 in 50 dilution) and E-cadherin (Dako; 1 in 150 dilution), oestrogen receptor- b (OR- b , AbD Serotec, Oxford, UK; 1 in 50 dilution), neuron-specific enolase (NSE, Dako; 1 in 200 dilution), vimentin (Dako; 1 in 100 dilution), p63 (Neo- Markers Inc., Fremont, California, USA; 1 in 200 dilution) and Ki67 (Dako; 1 in 100 dilution)and primary rabbit antibodies specific for chromogranin A (Dako; 1 in 200 dilution), PGP9.5 (Dako; 1 in 200 dilution) and synaptophysin (Dako; 1 in 200 dilution) and guinea pig antibody specific for insulin (Biomeda Corp., Foster City, California, USA; 1 in 400 dilution). The antibodies used were validated by noting a positive reaction with their corresponding normal tissues and a negative reaction on replacement with normal mouse or rabbit immunoglobulins. The Ki67 index was assessed by counting both Ki67-positive and Ki67-negative tumour cells in 10 randomly selected fields at  400 magnification and expressing the count as a percentage (Ki67-positive cells/total number of cells counted). For electron microscopical examination, small pieces of the formalin-fixed tumour tissue were refixed in 1% osmium tetroxide, followed by 0.2 M phosphate buffer, and then embedded in epoxy resin. Using an electron micro- scope, ultrathin sections were examined after staining with uranyl acetate and lead citrate. The mass was located in the subcutis and the cut surface was grey e white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells invaded the surrounding ducts and in general had small, round hypochromatic nuclei containing large prominent nucleoli and abundant faintly eosinophilic cytoplasm (Fig. 1). The fre- quency of mitotic figures was 0 e 1 per high-power (  400) field. The tumour cells were positive for argyr- ophilic granules with Grimelius stain (Fig. 1 inset), but they were negative for mucicarmine and PAS stains. No rosette structures were observed. A metastatic lesion was observed in the inguinal lymph node (Fig. 2). Immunohistochemically, most tumour cells were positive for CK AE1/AE3, CK20, CK8, chromogranin A (Fig. 3), NSE, synaptophysin, E-cadherin, OR- b and PGP9.5, but they were negative for vimentin, CAM5.2, p63 and insulin. The Ki67 index of the tumour was low (2.1%). Normal luminal and ductal cells of the mammary glands expressed both CK20 and OR- b , but not chromogranin A. The immunohistochemical features of the ...
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... cells were positive for argyr- ophilic granules with Grimelius stain (Fig. 1 inset), but they were negative for mucicarmine and PAS stains. No rosette structures were observed. A metastatic lesion was observed in the inguinal lymph node (Fig. 2). Immunohistochemically, most tumour cells were positive for CK AE1/AE3, CK20, CK8, chro- mogranin A (Fig. 3), NSE, synaptophysin, E-cad- herin, OR-b and PGP9.5, but they were negative for vimentin, CAM5.2, p63 and insulin. The Ki67 index of the tumour was low (2.1%). Normal luminal and ductal cells of the mammary glands expressed both CK20 and OR-b, but not chromogranin A. The immunohistochemical features of the metastatic tumour in the ...
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... These reports include a case study of a 10-year-old female border collie and a retrospective study of dogs. 5,6 The canine mammary NEC shares various histopathologic features that are consistent with those described in humans. Most canine mammary NEC cases showed moderate-sized cells with granular and vacuolar cytoplasm, or abundant faint eosinophilic cytoplasm with small, round to oval nuclei, suggesting the presence of large cell NEC. ...
... Immunohistochemical markers, such as TTF-1 and cytokeratin, are useful in the definitive diagnosis of pulmonary adenocarcinoma [3,6]. Histiocytic sarcomas or neuroendocrine carcinomas are immunopositive for vimentin, CD204 and Iba1 or chromogranin A and synaptophysin, respectively [7,8]. The present case was diagnosed as pulmonary adenocarcinoma due to positive immunolabelling for cytokeratin and TTF-1. ...
A 12-year-old castrated male Beagle dog presented with a 1-month history of progressive loss of appetite and cough. One month after the initial visit, a detailed clinical examination was performed due to weight loss and persistent cough. Computed tomography demonstrated diffuse opacification of the entire right lung and cranial lobe of the left lung. Samples of the pulmonary lesions obtained by fine-needle aspiration (FNA) were highly cellular with scattered and clustered foci of large round cells, suggestive of a round cell tumour. Ten days after the FNA, the dog was euthanized due to decreased activity and severe respiratory symptoms. At necropsy, enlargement of the entire right lung and cranial lobe of the left lung was seen. The external and cut surfaces of the lungs were homogeneously grey-white. Histopathological examination of sections of the right lung and the cranial lobe of the left lung revealed proliferation of large round or polygonal neoplastic cells arranged in nests of variable size separated by a thin fibrous stroma. Neoplastic cells were immunopositive for cytokeratin and thyroid transcription factor-1 but negative for vimentin, CD204, chromogranin A and synaptophysin. On the basis of these findings, the tumour was diagnosed as pulmonary solid adenocarcinoma.
... Only a few case reports document its presence in dogs. The liver, gallbladder, kidneys, gastrointestinal tract, nasal cavities, apocrine glands of the anal sac, mammary glands and skin were reported to be the place of occurrence of neuroendocrine carcinomas in dogs (Sako et al. 2005;Birettoni et al. 2008;Joiner et al. 2010;Ogawa et al. 2011;Nakahira et al. 2015;Morgan et al. 2019;Sozmen et al. 2020). Case reports, which describe the occurrence of neuroen-docrine carcinomas of the heart, exist in human literature (Guajardo-Salinas et al. 2013;Wißt et al. 2018). ...
A case of a nine-year-old, intact female, American Bulldog with a heart mass is described. Echocardiography was used to identify this pathological lesion. Part of the mass and pericardial sac were surgically removed for histopathological examination. A final diagnosis of neuroendocrine carcinoma was diagnosed by necropsy and histopathology. To the author’s knowledge, there is very limited information in the literature about this pathology.
... Neuroendocrine carcinoma of the mammary gland was first recognized in women by Feyrter and Hartmann (1963) and in dogs by Nakahira et al (2015). This tumour occurs with low frequency in women and represents 0.5e1% of all breast cancers. ...
Mammary neoplasms are the most frequently diagnosed tumours in female dogs and are classified into various histological types, including solid carcinomas. We proposed a subclassification of solid carcinomas based on morphological and immunohistochemical characteristics, and correlated the subtypes with prognostic factors. A total of 135 cases of solid mammary carcinoma were selected from 3,400 canine mammary neoplasms in the archives of the Laboratory of Comparative Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil. Epidemiological and survival data were obtained, and immunolabelling for chromogranin A, pancytokeratin, cytokeratin 14, Ki67 and p63 was performed. Solid carcinomas were classified into six subgroups: malignant adenomyoepithelioma (68/135), carcinoma with solid pattern (22/135), malignant myoepithelioma (16/135), basaloid carcinoma (14/135), neuroendocrine carcinoma (10/135) and solid papillary carcinoma (5/135). Shorter survival time was associated with the presence of lymphatic invasion (P = 0.009) in the initial clinical staging (I–III). When considering all clinical stages (I–V), vascular invasion (P <0.001) and the presence of regional metastasis (P = 0.004) were important prognostic factors. Basaloid carcinoma and solid papillary carcinoma did not reach the median survival time for early-stage cases, and malignant myoepithelioma had the highest median survival in advanced stages. Carcinoma with a solid pattern was associated with a higher number of regional metastases. Distinguishing the various histological and immunophenotypic subtypes that exhibit a solid arrangement, using histological and immunohistochemical criteria, is essential for understanding the behaviour of these neoplasms and for the selection of more appropriate and specific therapies.
... Neuroendocrine tumors are a group of biologically and clinically heterogeneous neoplasms that originate most commonly in lungs, gastrointestinal tract and pancreas (1,2). Although their occurrence is rare, pure neuroendocrine tumors and invasive breast carcinomas with neuroendocrine features have already been reported in women (3)(4)(5), while only one case has been reported in a female dog (6). ...
... Invasive carcinomas with neuroendocrine differentiation of the human breast are under-recognized in the practical routine and represent 0.5-1% of all breast cancers (11,12,15). In veterinary medicine, this histological type is not yet well recognized, with a single prior case report in the literature (6), making ours the first retrospective study on neuroendocrine carcinomas in the female dog. ...
Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.
Nasal tumors account for less than 10% of all feline neoplasms, with lymphoma, followed by adenocarcinoma, and squamous cell carcinoma, the most commonly reported. Nasal neuroectodermal tumors, including olfactory neuroblastoma (ONB), are scarcely described, and their tumorigenesis is largely unknown. Here we report the cytological, histological, and immunohistochemical features of a feline ONB. We also provide a pathological review of nasal neuroendocrine neoplasms in cats. A 7-year-old Burmese cat was evaluated for sneezing, occasional epistaxis, and upper respiratory noise for 8 months. Computed tomography (CT) imaging revealed a 7 × 5 × 3 mm irregular mass effacing and expanding the nasal cavity, which extended to the nasopharynx. Cytologically, neoplastic cells were round to polygonal and had a round nucleus with finely stippled chromatin, a single small nucleolus, and abundant pale blue cytoplasm, which contained abundant fine pale pink granules. They exhibited mild cellular atypia, anisocytosis, and mild to occasionally moderate anisokaryosis. Rhinoscopic biopsies revealed a densely cellular, malignant neuroepithelial neoplasm. Cells were arranged in densely packed trabeculae and formed Homer Wright and Flexner-Wintersteiner-like rosettes, with rare mitotic figures and scant supportive fibrovascular stroma. Immunohistochemically, neoplastic cells were positive for vimentin, cytokeratin AE1/AE3, COX-2, and beta-tubulin and negative for S-100, chromogranin A, CD117, and epithelial membrane antigen (EMA). An ONB was diagnosed based on histological and immunohistochemical findings. Interestingly, and similar to nasal carcinomas, neoplastic cells diffusely neo-expressed COX-2. To the authors' knowledge, there is no previous evidence of COX-2 in feline ONB. Histopathology and immunohistochemistry are required for a definitive diagnosis of ONB.
A 9‐year‐old male neutered Cockerpoo dog was presented with pyrexia and was diagnosed with sterile idiopathic panniculitis. During initial investigations, advanced imaging revealed a suspected left‐sided cervical paraganglioma and bilateral adrenal masses. The dog underwent immunosuppression and achieved remission of the sterile idiopathic panniculitis. Bilateral adrenalectomy and paraganglioma excision were then performed. Histopathology identified bilateral adrenocortical carcinoma and cervical neuroendocrine carcinoma. Three months later, the dog was diagnosed with primary hyperparathyroidism. Despite left total thyroidectomy and parathyroidectomy, mild hypercalcaemia persisted for several months. Eight months later the dog became persistently hypokalaemic refractory to potassium supplementation, had metabolic alkalosis and systemic hypertension. The dog was euthanised 5 months later due to clinical deterioration. On post‐mortem examination, right parathyroid hyperplasia and metastatic neuroendocrine carcinoma involving liver, jejunum, pancreas and tracheobronchial lymph node were identified. This is the first report describing the concurrent presence of these types of endocrine neoplasms in a dog.
Primary small cell carcinomas are rare in domestic animals. A mass measuring 15 × 20 × 9 cm was detected in the left abdominal cavity of a 7.5-year-old female golden retriever. The cut surface of the excised mass showed a tumour replacing the left kidney. Microscopically, the mass was composed of polymorphic, small basophilic cells with a high nuclear to cytoplasmic ratio and round, oval or short slender fusiform nuclei with condensed or finely granular chromatin, absent or inconspicuous nucleoli, and scant, faintly eosinophilic cytoplasm with poorly defined cytoplasmic borders. Immunohistochemically, most of the neoplastic cells were immunoreactive for thyroid transcription factor 1 and CD56, moderately positive for vimentin and weakly or sparsely labelled for chromogranin A, synaptophysin, Wilms' tumour 1 protein, neuron-specific enolase, pan-cytokeratin (CK) AE1/AE3 and epithelial membrane antigen. The tumour cells were negative for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1, CK7, CK20, CD3, CD45 and CD99. These findings indicated a neuroendocrine origin of the tumour. To the best of author's knowledge, this is the first report of a small cell neuroendocrine carcinoma originating as a primary tumour in the kidney of a dog.
Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident. Cellular atypia was minimal, and no mitotic figures were visible. One tumor had several oncocytic cellular foci revealing cellular transition, with perivascular pseudorosettes consisting of columnar epithelial cells surrounding the fine vasculature. Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein, mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A. One tumor also had oncocytic cellular foci forming perivascular pseudorosettes showing cellular membrane immunoreactivity for neural cell adhesion molecule. The tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin, desmin, S100, and synaptophysin. Ultrastructural observation confirmed the abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells, the former cells also having neuroendocrine granule–like electron-dense bodies. From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas.
