Calcification in the primary intestinal tumor is a very rare finding in both human and veterinary literature (2,5). In humans, the calcified primary tumors in mesentery, peritoneum, retroperitoneum, liver, gallbladder, pancreas, adrenal glands, kidney, urinary bladder, uterus, penis, colon, appendix, and lymph node have been documented (9). In dogs, the calcified primary tumors in the liver, pancreas, adrenal gland, prostate, mammary glands, and ovaries have been documented (5). Calcification in tumors usually follows a cellular injury, such as tissue necrosis, inflammation, and hemorrhage (3). Abnormal calcium deposition in soft tissue can be divided based on two mechanisms: metastatic and dystrophic forms. Metastatic calcification refers to mineral deposits in the undamaged normal tissue caused by persistent systemic calcium imbalance (1). Dystrophic calcification is usually considered as calcium deposition in the degenerating tissues or necrotic tissues in the presence of normal plasmatic levels of calcium. It has been suggested that local alkalinity in necrotic tissue is suitable for calcium deposition (1). Calcification in primary intestinal tumor has been described in diverse neoplasms of the intestinal tract including mucinous carcinoma, gastrointestinal stromal tumor, carcinoid tumor, and leiomyosarcoma in humans (8). To the author’s knowledge, calcification of undifferentiated carcinoma has not yet been reported in both human and veterinary literature. The purpose of this study is to describe a calcified primary intestinal tumor based on diagnostic imaging in a dog.

An eight-year-old, intact female, Shih-Tzu, weighing 4.5 kg presented with complaints of anorexia, pale mucous membrane, and vomiting for the past 5 days. On physical examination, nausea, abdominal pain, and melena were noted. Based on a complete blood count examination, microcytic normochromic regenerative severe anemia and thrombocytosis were identified: hematocrit of 8.5% (reference range, 37.3-61.7%), reticulocyte of 157.8 k/μL (reference range, 10-110 k/μL), and platelet of 591 k/μL (reference range, 148-484 k/μL). On venous blood gas analysis, hyperlactatemia was identified: lactate of 4.2 mmol/L (reference range, 0.5-2.5 mmol/L). On biochemistry examination, hypertriglyceridemia and hyperlipasemia were identified: triglyceride of 149 mg/dL (reference range, 10-100 mg/dL) and lipase of 6000 U/L (reference range, 200-1800 U/L). Canine pancreas specific lipase test (Canine SNAP cPL; IDEXX Laboratories Inc., Westbrook, ME, USA) revealed abnormal results. The patient was transfused to reach the target hematocrit of 49% (packed RBC, total transfused volume 268 mL). After transfusion, hematocrit was confirmed to be 36%, and lactate was confirmed to be in the normal range as 1.2 mmol/L.

On radiographic examination (X-ray tube: Toshiba Electron Tubes and Devices Company, Tokyo, Japan; computed radiography system: Regius model 190^®, KONICA Minolta, Japan; 54 kVp, 400 mA, 6.3 mAs), soft tissue opacity mass with small faint mineral opacity in the mid-abdomen and two mineral opacity regions in the cranial aspect of mass were identified (Fig. 1). Soft tissue opacity mass with small faint mineral opacity was considered intestinal mass, ovarian mass, enlarged mesenteric lymph node, or granuloma. Two mineral opacity regions were considered dystrophic calcification, feces, and foreign bodies.

Figure 1. Ventrodorsal (A) and right lateral (B) abdominal radiographs of the patient. Soft tissue opacity with small faint mineral opacity mass in the mid-abdomen (arrow head) and two mineral opacity regions in the cranial aspect of mass (arrow) were identified.

Ultrasonographic (US) (Arietta70, Hitach Aloka Medical, Tokyo, Japan; 2-12 MHz linear probe) findings showed circumferential thickening of the descending duodenal wall adjacent to the caudal duodenal flexure up to 1.15 cm with loss of wall layering. Multifocal hyperechoic foci accompanied by twinkle artifact within thickened duodenal wall on the color Doppler were identified. Regional lymph node enlargement was identified. Adjacent to the duodenal lesion, curve-linear shaped hyperechoic lesion measuring up to 1.9 cm with posterior acoustic shadowing was identified (Fig. 2). Hypoechoic change of pancreatic parenchyma and hyperechoic change of peripancreatic fat were identified. Thickening of the descending duodenal wall with loss of wall layering and multifocal hyperechoic foci were considered duodenal tumor or chronic inflammation with dystrophic calcification. The curve-linear-shaped hyperechoic lesion was considered calcification of mesenteric fat, but the possibility of the calcified ectopic pancreas was not ruled out. The enlarged regional lymph node was considered reactive lymphadenopathy. A small volume of ascites in the overall abdominal cavity and pancreatitis were also identified.

Figure 2. Abdominal ultrasonographic images of the patient. (A, B) Thickening of the descending duodenal wall with loss of layering (arrow) and calcification within the duodenal wall (asterisk) was found. Calcification within the mesentery adjacent to the duodenal lesion (arrow head) was observed. A small number of twinkle artifacts were identified.

At the request of the owner, a non-anesthetic CT (Aquilion Lightning 160, Canon Medical Systems, Otawara, Japan) scan was performed. Non-contrast computerized tomography (CT) showed that descending duodenal wall from the distal part of the descending duodenum to the duodeno-jejunal junction was thickened by up to 8 mm and small mineral attenuating material (mean 110 HU) in this duodenal lesion was identified. Mild gaseous dilation of proximal duodenum and fluid-filled dilation of jejunum were identified. A 1.3 cm sized, irregular-shaped soft-tissue attenuating the lesions with mineral attenuating materials was identified in the mesentery adjacent to the duodenal lesion. Calcification of enlarged regional lymph node (1.1 cm sized) was also identified (Fig. 3). Circumferential wall thickening of descending duodenum with calcification is considered a calcified duodenal tumor. However, the possibility of chronic inflammatory disease with dystrophic mineralization was not ruled out. The dilated small intestine was considered inflammatory changes. Calcification of mesentery and mesenteric lymph node were considered metastasis. However, the possibility of granulation tissue related to chronic inflammation with dystrophic calcification and reactive lymphadenopathy was not ruled out.

Figure 3. Non-contrast computed tomography images of the patient. Transverse view (A) and sagittal view (C) show circumferential wall thickening of descending duodenum with calcification (arrow). In transverse view (B) and sagittal view (D, E) calcification of the mesentery (asterisk) and mesenteric lymph node (arrow head) were identified.

Based on the diagnostic imaging, the tentative diagnosis was descending duodenal tumor with dystrophic calcification. Endoscopy revealed mucosal hemorrhage and erythema within the descending duodenum and stomach. Because of the length of the endoscope, the distal part of the duodenum and duodeno-jejunal junction were not identified.

The surgery was performed, and thickening of descending duodenum wall and calcification in the pancreatic tail to the duodenum and mesentery were found. The lesion site was found to adhere to the ileocolic junction, and major blood vessels of the mesentery and caudal vena cava (Fig. 4). A mass extending from the duodenum to the mesentery and the tail of the pancreas was resected. And duodenum anastomosis was performed. The histologic examinations revealed a high-grade undifferentiated carcinoma with intraabdominal metastases to the regional lymph nodes (Fig. 5). The tumor extended diffusely throughout the submucosa, mucosa, and muscle tunic, and focally into the peritoneal adipose tissue. Neoplastic cells form irregular nodular structures, cords, or broad sheets, and are often accompanied by acute coagulation necrosis. Lymph node architecture has been replaced by the metastatic tumor. This tumor extends diffusely throughout the peritoneal connective tissue and directly to the tissue margins.

Figure 4. Duodenum, mesenteric lymph node, and mesenteric mass in the surgical biopsy specimen. Thickening of the descending duodenum wall and calcification in the pancreatic tail to the duodenum (arrow head) and mesentery (arrow) were found.

Figure 5. Histopathology of the excision biopsy of the intestinal undifferentiated carcinoma. Tumor invasion to the mucosa (arrow), submucosa (asterisk), and muscle tunic (arrow head), and focally into the peritoneal adipose tissue can be seen. Scale bars: (A) 5 mm, (B) 50 μm.

Five days later, a US showed the absence of the duodenal, mesentery, and mesenteric lymph node lesion, which had been previously identified. Hence, the patient was treated with medication for 8 days and discharged. A week later, the patient was readmitted with the complaint of pale mucous membrane and vomiting. On hematologic examination, anemia was identified: hematocrit of 22.8% (reference range, 37.3-61.7%). No complications were identified during the follow-up period for 5 months after transfusion.

The tumor cells of undifferentiated carcinoma lack the cytological features of the typical epithelial tumor and have a high nuclear-cytoplasmic ratio with indistinct cellular borders within the mucosa, submucosa, and the muscular layer (7). According to a previous study on humans, clinical manifestations and diagnostic imaging features of undifferentiated carcinoma are similar to other intestinal tumors (6). Furthermore, the most common primary site of the tumor is the jejunum and ileum, and it usually tends to involve the adjacent serosa and lymph nodes (6). In the present report, a similar and very aggressive carcinoma was identified at each of the 3 sites: duodenum, mesenteric lymph node, and mesentery. The tumor was relatively undifferentiated and was considered to be of intestinal or possibly exocrine pancreatic origin. There exist a high potential for local recurrence of the tumor at each site and metastasis throughout the peritoneal cavity. The clinical signs and symptoms in this case were anorexia, vomiting, abdominal pain, melanoma, and anemia, which were common symptoms in intestinal tumors. Diagnostic imaging features were similar to that of other intestinal tumors in a dog except for calcification.

Calcification in tumors usually follows a cellular injury, such as tissue necrosis, inflammation, and hemorrhage (1). Calcification in tumor is commonly seen in association with certain benign and malignant tumors (9). In treatment-naive malignant tumors, calcifications are often associated with internal necrosis or high mucus content, the former indicative of poor differentiation of tumor cells (9). However, tissue damage due to inflammation can also cause calcification. In humans, sclerosing mesenteritis has also been identified as a calcified mass (9). Tissue damage causes endogenous calcium release from the mitochondrial and endoplasmic reticulum reserves, which is augmented by increased exogenous calcium entry through the damaged cell membrane (1). The alkaline environment promotes phospholipase enzymatic activity within the cells that lead to the formation of free acids from phospholipids, thereby leading to the formation of soaps that become visible as dystrophic calcification (1). Because of the higher attenuation coefficient, calcium absorbs more photons than the soft tissues; hence calcium appears radiopaque on plain abdominal radiographs (9). In the present report, multifocal small-sized faint mineral opacities superimposed with soft tissue mass and two mineral opacity regions in the cranial aspect of the mass were detected on abdominal radiographs. During the US, the ultrasound beam is almost completely reflected by calcium due to its high density (9). Calcification appears hyperechoic and is related to clean posterior acoustic shadowing (9). In the present report, US findings showed thickening of the descending duodenal wall with loss of layering and calcification within the duodenal wall and adjacent to the duodenal lesion. CT images are considered better than radiographs for the detection of calcium deposition. For calcium deposition assessment, non-enhanced CT benefits from more straightforward image interpretation, with an attenuation of greater than approximately 100 HU as essentially diagnostic (4). In the present report, non-contrast CT showed symmetric thickening of the descending duodenal wall with calcification, calcified nodule in the mesentery, and calcified mesenteric lymph node. We thus surmised that the calcified lesions in the patient were associated with cellular injury due to neoplasia.

A limitation of this study was that no additional immunohistochemistry was performed. Therefore, it was not possible to determine whether the origin of the tumor was the pancreas or the small intestine. However, based on diagnostic imaging and surgical approaches, the tumor was likely to originate from the intestine because it surrounded the intestine and extended to the surrounding area.

The present case describes that an undifferentiated carcinoma (a rare tumor in the small intestinal) should also be considered when diagnosing mineralized tumors in the small intestine through radiography, US, and CT. However, histopathological examination is essential for the confirmation of undifferentiated carcinoma.

This work was supported by the Animal Medical Institute of Gyeongsang National University.

The authors have no conflicting interests.