Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic,immunohistochemical, and molecular genetic study of 50 cases

Fifty canine gastrointestinal (GI) mesenchymal tumors were examined to determine the occurrence of leiomyomas (LM) and GI stromal tumors and to compare their clinicopathologic features. Twenty-one tumors (42%) were histologically reclassified as gastrointestinal stromal tumors (GISTs) and 29 tumors (58%) as LMs on the basis of their histologic similarity with homologous human tumors. The GISTs occurred equally in males and females, with a mean age of 11 years (range 5-14 years). Five GISTs (24%) were associated with clinical signs and six (29%) had metastasis in liver or abdominal cavity. The GISTs occurred in large intestine (10, 48%), small bowel (six, 29%), stomach (four, 19%), and mesentery of small intestine (one, 5%). Histologically, they were highly cellular spindle, or less commonly epithelioid tumors with mitotic rates ranging from 0 to 19 per 10 HPF. Eleven tumors (52%) were positive for CD117 (KIT); seven (33%) were positive for smooth muscle actin but none for desmin and S-100 protein. Sequences of KIT exon 11, often mutated in human GISTs, were evaluated from four GISTs. Deletion of Try556-Lys557 coexisting with duplication of Gln555 in one case of GIST and T to C transition resulting in substitution of Pro for Leu575 in another were identified. The LMs occurred predominantly in males (82%) with a mean age of 11 years (range 8-17 years). Nine tumors (31%) had associated clinical signs. They occurred in the stomach (22, 76%), esophagus (four, 14%), and intestines (three, 10%); all were paucicellular, had no mitoses, and were composed of mature smooth muscle cells. Twenty-eight (97%) were positive for smooth muscle actin and 18 (62%) for desmin but none for CD117 and S-100. Both GISTs and true LMs occur in the GI tract of dogs. Both tumors have distinctive pathologic features.     

Immunohistochemical Differentiation and Clinicopathological Features of Canine Gastrointestinal Stromal Tumors and Leiomyosarcomas

Introduction:  Gastrointestinal stromal tumors (GIST) and leiomyosarcomas (LMS) have recently been differentiated by immunohistochemical staining techniques and have been shown to have different biological behaviors in humans. Expression of the c‐kit protein, a transmembrane tyrosine kinase receptor, occurs in nearly all GISTs. The aim of this study was to differentiate canine GIST from LMS, and to compare their clinicopathological features.
Methods:  Archived blocks of previously diagnosed LMS were analyzed. Immunohistochemical staining using antibodies against c‐kit, smooth muscle actin (SMA), desmin, vimentin and S100 was performed. GISTs were diagnosed based on positive c‐kit staining. LMS were diagnosed based on absence of c‐kit staining and positive SMA staining. Follow‐up information was obtained from medical records and telephone interviews with owners.
Results:  Forty‐two dogs were included in the study. Mean age was 10.9 yrs (range 5–15 yrs). There were 18 females and 24 males. Twenty‐eight tumors were GISTs, 10 were LMS and 4 stained negatively for c‐kit, SMA and S100 (sarcomas). GISTs were more likely to occur in the large intestine and LMS were more common in the small intestine (p = 0.01). All were surgically excised and only two were treated with adjunctive chemotherapy. Only two GISTs and one sarcoma had metastasized at the time of surgery. Survival time in dogs discharged after surgery for GIST, LMS and sarcomas was 1123, 233 and 88 days respectively (p = 0.08).
Conclusions:  Many previously diagnosed LMS should be reclassified as GIST based on the results of immunohistochemical staining. The biological behavior of these tumors appears to be different.     

Imatinib mesylate treatment in a dog with gastrointestinal stromal tumors with a c-kit mutation

A 13-year-old spayed mixed-breed dog was diagnosed with a gastrointestinal stromal tumor (GIST) after histopathological examination of an abdominal mass. Five months after surgical resection of the tumor, we detected the recurrence of GIST with multiple disseminated abdominal lesions. A sequence analysis of cDNA obtained from a biopsy of the recurrent tumors revealed a mutation within exon 9 of the c-kit gene (1523A>T, Asn⁵⁰⁸Ile), which has been shown to cause ligand-independent phosphorylation of the KIT protein in GISTs and canine mast cell tumors (MCTs). Upon detection of the recurrent tumors, we initiated treatment with imatinib mesylate (10 mg/kg, q 24 hr). After 2 months, the dog achieved complete remission. Our findings indicate that canine GIST, and possibly MCT, may be responsive to molecular-targeted therapy.     

Gastrointestinal stromal tumors in equids.

Eleven gastrointestinal neoplasms from 10 aged horses and 1 pony were examined grossly, his tologically, immunohistochemically, and (in two cases) ultrastructurally. Clinical signs were associated with two neoplasms, and the other nine tumors were incidental findings at laparotomy or necropsy. The neoplasms were solitary (9/11) or multifocal (2/11), well demarcated, serosal or mural masses of stomach (1), jejunum (1), ileum (3), cecum (5), and/or colon (2). Microscopic examination revealed discrete spindle cells arranged in compact patterns with fascicles and whorls or cribriform pattern with fascicles and rare palisades, often with a myxoid interstitial matrix. Three tumors infiltrated between the muscularis interna and the muscularis externa at the myenteric plexi. All neoplasms were vimentin positive, 3/11 were S-100 positive, 2/11 were muscle actin positive, and no neoplasm was positive for glial fibrillary acid protein, desmin, factor VIII, chromogranin, or neuron-specific enolase. Of the two tumors studied ultrastructurally, one contained an admixture of smooth muscle cells and cells resembling Schwann cells, and the second was populated by homogeneous fusiform mesenchymal cells separated by homogeneous matrix. Gastrointestinal stromal tumors (GIST) have been recognized in humans, more recently in dogs and nonhuman primates, and now in equids. Most of these tumors are comprised of a loosely arranged network of spindled cells separated by myxoid matrix. GIST may be composed of myogenic, neurogenic, combined myogenic and neurogenic, and undifferentiated mesenchymal cells.     

Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic, and immunohistochemical evaluation

Objectives— To reclassify canine small intestinal and cecal leiomyoma (LM) and leiomyosarcoma (LMS) into smooth muscle and gastrointestinal stromal tumors (GIST) using histologic and immunohistochemical (IH) analysis and to report clinical findings and survival data.
Study Design— Retrospective review of cases.
Animals— Dogs (n=47) with small intestinal (40 LMS; 7 LM) and 25 dogs with cecal tumors (23 LMS; 2 LM).
Methods— Clinical and survival data were reviewed. Tissue sections were reevaluated for light-microscopic malignancy criteria and examined for expression of SMA, desmin, vimentin, S-100, and CD117 (KIT) by immunohistochemistry.
Results— Reclassification resulted in 2 LM, 9 LMS, 19 GIST, and 17 GIST-like tumors in the small intestine and 23 GIST and 2 GIST-like tumors in the cecum. GIST-like tumors were morphologic and IH identical to GIST but lacked KIT expression. No significant difference in survival was observed for tumor type, location, histologic, or IH characteristics; however, dogs with cecal tumors were significantly older in age, presented more commonly with intestinal perforation and peritonitis, and less commonly with weight loss. Cecal tumors had more histologic malignancy criteria than small intestinal tumors. After excision, 1 and 2 year recurrence-free periods were 80.1% and 67.2% for small intestinal and 83.3% and 61.9% for cecal tumors.
Conclusion— Prognosis for intestinal tumors with histologic smooth muscle appearance is good after excision and not related to tumor type, location, histologic, or IH characteristics.
Clinical Relevance— Clinical importance could not be demonstrated for reclassification, but may be for future treatment, of intestinal smooth muscle or stromal tumors.     

Three cases of canine gastrointestinal stromal tumors with multiple differentiations and c-kit-expression

Three canine gastrointestinal stromal tumors (GISTs) were examined. Histopathologically, the tumor mass in the jejunum (Case 1) consisted of the proliferation of epithelioid cells with abundant eosinophilic or vacuolated cytoplasm. Gangliocyte-like or multinucleated giant cells were scattered. The tumor cells exhibited neural natures mimicking human gastrointestinal autonomic nerve tumors, which were immunopositive for several neuronal markers. Another jejunal mass (Case 2) was composed by a solid proliferation of spindle-shaped cells, arranging in interlacing fascicles and occasional storiform pattern. The tumor seemed to be classified undifferentiated GISTs, that showed no apparent neural or muscular features by ultrastructural and immunohistochemical examinations. In the pyloric mass (Case 3), the spindle cells having eosinophilic processes and elongated nuclei were arranged in sheets. Immunohistochemically, the tumor cells showed muscular natures as regards alpha smooth muscle actin and desmin expression.     

Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (Macaca mulatta)

Multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus macaque (Macaca mulatta) experimentally infected with simian immunodeficiency virus, strain SIVsmE660, and CD4+ T cell depleted. The animal was negative for simian retroviruses, SRV-1, -2, and -5. Polymerase chain reaction analysis of DNA from tumor and spleen tissue revealed abundant, preferential presence of retroperitoneal fibromatosis herpesvirus, the macaque homologue of the Kaposi sarcoma-associated herpesvirus (human herpesvirus-8), in the tumors. This was corroborated by demonstration of viral latent nuclear antigen-1 in the nuclei of a majority of the spindeloid tumor cells. Low levels of an additional macaque herpesvirus, rhesus rhadinovirus, were also detected in the spleen and tumor tissues. The spindeloid cells labeled positively for vimentin and CD117 but were negative for CD31, CD68, desmin, and smooth muscle cell actin. Collectively, these findings suggest a relation to but not absolute identity with simian mesenchymoproliferative disorders (MPD) or typical gastrointestinal stromal tumors (GISTs).     

Endometrial stromal tumor in a chimpanzee.

A 25-year-old female chimpanzee with disseminated tuberculosis also had two uterine tumors. One a typical leiomyoma and the other, which occluded the uterine lumen, was composed of cells resembling normal endometrial stroma in its proliferative phase. It was diagnosed as an endometrial stromal tumor and was similar to that which occurs in the human female. This is the first report of this lesion in a nonhuman primate.     

Analysis of KIT expression and KIT exon 11 mutations in canine oral malignant melanomas

KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for anti-cancer therapy. In humans, its expression and mutations have been identified in malignant melanomas and therapies using molecular-targeted agents have been promising in these tumours. As human malignant melanoma, canine malignant melanoma is a fatal disease with metastases and the poor response has been observed with all standard protocols. In our study, KIT expression and exon 11 mutations in dogs with histologically confirmed malignant oral melanomas were evaluated. Although 20 of 39 cases were positive for KIT protein, there was no significant difference between KIT expression and overall survival. Moreover, polymerase chain reaction amplification and sequencing of KIT exon 11 in 17 samples did not detect any mutations and proved disappointing. For several reasons, however, KIT expression and mutations of various exons including exon 11 should be investigated in more cases.     

Subcutaneous neoplasms of the ventral abdomen with features of adrenocortical tumors in two ferrets

A ventral abdominal subcutaneous mass was removed from each of 2 young adult spayed female ferrets. In both cases, the neoplasms were composed of islands of polygonal cells separated by interlacing streams of spindloid cells reminiscent of ferret adrenocortical tumors with smooth muscle proliferation. Immunohistochemically, the polygonal cells demonstrated strong cytoplasmic reactivity for inhibin and weak cytoplasmic reactivity for pancytokeratin and S-100 protein. Spindloid cells demonstrated strong cytoplasmic reactivity for alpha smooth muscle actin, muscle-specific actin, desmin, and glial fibrillary acidic [corrected] protein. Ultrastructurally, the polygonal cells contained numerous intracytoplasmic clear vacuoles, mitochondria, scant rough endoplasmic reticulum, and few intermediate filaments. In one tumor, vesicular tubular mitochondria were found in polygonal cells. The spindloid cells contained numerous aggregates of parallel intermediate filaments. The histologic, immunohistochemical, and ultrastructural findings are suggestive of adrenocortical tumors with smooth muscle proliferation, but cannot be differentiated from an ovarian gonadal stromal tumor. Neither ferret had a clinically detected primary adrenal gland tumor or clinical signs of adrenal-associated endocrinopathy.     

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.     

ULTRASONOGRAPHIC FEATURES OF CANINE GASTROINTESTINAL STROMAL TUMORS COMPARED TO OTHER GASTROINTESTINAL SPINDLE CELL TUMORS

Canine gastrointestinal stromal tumors (GISTs) are a recent subtype of gastrointestinal spindle cell tumor recognized with the increasing use of immunohistochemistry. To our knowledge, no imaging features have been described in immunistochemically confirmed canine GISTs. The objective of this retrospective, cross‐sectional study was to describe ultrasonographic features of canine GISTs compared with other spindle cell tumors. Thirty‐seven dogs with an ultrasonographically visible gastrointestinal mass and a histopathologic diagnosis of spindle cell neoplasia were examined. Immunohistochemistry staining was performed for retrieved tissue samples to further differentiate the tumor type and each sample was interpreted by a single veterinary pathologist. Ultrasonographic features recorded examined included mass echogenicity, homogeneity, presence of cavitation, layer of origin, bowel wall symmetry, and loss of wall layering, location, size, vascularity, and evidence of perforation or ulceration. Tumor types included 19 GISTs, eight leiomyosarcomas, six leiomyomas, and four nonspecified sarcomas. Gastrointestinal stromal tumors were significantly more likely to be associated (P < 0.03) with abdominal effusion than other tumor types. There was overlap between the anatomical locations of all tumors types with the exception of the cecum where all eight tumors identified were GISTs. Besides location, there were no unique ultrasound features of GISTs that would allow distinction from other gastrointestinal spindle cell tumors. Similar to previous studies, GISTs appeared to be the most common spindle cell tumor associated with the cecum in our sample of dogs. The high frequency of abdominal effusion with GIST's was of unknown etiology could possibly have been due to septic peritonitis.     

Myxoid leiomyosarcoma of the gizzard in a broiler chicken

A leiomyosarcoma was found in the gizzard of a 57-day-old female broiler chicken weighing 1.8 kg. Grossly, the tumor mass, 13.0 x 8.5 x 10.0 cm, enveloped the gizzard and had a gelatinous appearance due to the rich production of mucin. Miliary metastatic tumors were noted in the liver. Histopathologically, there was marked production of mucus throughout the tumor tissue, and densely or loosely arranged long spindle-shaped leiomyosarcoma cells proliferated. The tumor cells had a low rate of mitosis, showed slight cellular atypia, and, immunohistochemically, were positive for actin, alpha-smooth muscle actin, and desmin. Electron microscopically, various amounts of microfibrils with focal densities, dense patches, and basal plates were observed.     

Myxosarcomas associated with avian leukosis virus subgroup A infection in fancy breed chickens

Formalin-fixed suspect tumors were submitted to the Poultry Diagnostic and Research Center at the University of Georgia (Athens, GA) for diagnosis. Samples were from fancy breed chickens with a history of increased tumor prevalence in both hens and roosters. Microscopically, in all the samples, there were neoplastic proliferations of spindle-shaped cells. The matrix surrounding tumor cells stained positively with Alcian blue at pH 2.5, but neoplastic cells did not stain with periodic acid-Schiff. Immunohistochemistry stains were positive for vimentin and neuron-specific enolase and negative for desmin, smooth muscle actin, and S-100 protein. Tumors were determined to be myxosarcomas. All samples were positive for PCR targeting the gp85 avian leukosis virus (ALV) envelope protein. However, analysis of the predicted amino acid sequences in the envelope gene from three separate samples showed high similarity between them and to ALV subgroup A.     

Gastrointestinal stromal tumors of the equine cecum

Ten cecal tumors were identified during the postmortem examination of seven horse carcasses at slaughter (one horse had three tumors). The multinodular and hemorrhagic tumors ranged from 1 to 10 cm in diameter and consisted of spindle cells arranged in thin, interconnected trabeculae that were often separated by sinuses filled with mucinous fluid, erythrocytes, and siderophages. Spindle cells of all tumors were immunopositive for vimentin, neuron-specific enolase, and c-kit protein but lacked reactivity with antibodies to glial fibrillary acidic protein, S100 protein, and desmin. In one tumor, spindle cells diffusely bound antibodies to synaptophysin. Most tumors contained focal reactivity to smooth muscle actin antibodies; one tumor reacted diffusely. Ultrastructurally, tumor cells were connected by desmosome-like structures and exhibited extended cell processes; some contained dense core neurosecretory granules. These equine stromal tumors appeared to share some characteristics with human gastrointestinal stromal tumors.     

Immunohistochemical characterization of nonhuman primate ovarian sex cord-stromal tumors

This study evaluates the immunoreactivity of 12 sex cord-stromal tumors of nonhuman primates (11 granulosa cell tumors and 1 luteoma). The markers selected are used in the characterization of gonadal tumors in dogs and other species, including cytokeratins AE1/AE3, GATA-4, inhibin-α, neuron-specific enolase, protein gene product 9.5, and vimentin. A normal nonhuman primate ovary was used as a control and to optimize immunolabeling. Staining was graded as follows: 0 (nonstaining), 1+ (< 10% positive cells), 2+ (10%-50% positive cells), and 3+ (> 50% positive cells). Calretinin, GATA-4, neuron-specific enolase, and vimentin were the most consistently expressed markers (12 of 12). Cytokeratins AE1/AE3 were also consistently expressed (11 of 12). Inhibin-α and protein gene product 9.5 were expressed in 8 and 10 sex cord-stromal tumors, respectively. Results indicate that immunoreactivity of nonhuman primate sex cord-stromal tumors is similar to that observed in other species and that calretinin, GATA-4, and neuron-specific enolase are the most consistently expressed markers in nonhuman primate sex cord-stromal tumors.     

Clinical and pathologic features of oligodendrogliomas in two cats

Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.     

Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003)

OBJECTIVE: To reexamine (via immunohistochemical techniques) canine tissue samples that had been previously classified as gastrointestinal leiomyosarcomas (GILMSs), identify and differentiate gastrointestinal stromal tumors (GISTs) from GILMSs, and compare the biological behavior and clinical course of GISTs and GILMSs in dogs. DESIGN: Retrospective case series. ANIMALS: 42 dogs. PROCEDURES: Medical records of 42 dogs for which a histologic diagnosis of GILMS was confirmed were reviewed for signalment, clinical signs, physical examination findings, results of initial diagnostic tests, surgical findings, adjunctive treatment, location of the tumor, completeness of resection, and outcome after surgery. Archived tumor tissue specimens from each dog were restained via immunohistochemical techniques to differentiate tumor types. Long-term follow-up information was obtained from the medical record or through telephone interviews with owners and referring veterinarians. RESULTS: On the basis of immunohistochemical findings, 28 of 42 tumors were reclassified as GISTs and 4 were reclassified as undifferentiated sarcomas; 10 tumors were GILMSs. In dogs, GISTs developed more frequently in the cecum and large intestine and GILMSs developed more frequently in the stomach and small intestine. Median survival times for dogs with GISTs and GILMSs were 11.6 and 7.8 months, respectively; if only dogs surviving the perioperative period were considered, median survival times were 37.4 and 7.8 months, respectively. These differences, however, were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, many previously diagnosed GILMSs should be reclassified as GISTs on the basis of results of immunohistochemical staining. The biological behavior of these tumors appears to be different.     

Uterine neoplasia in 13 cats.

Thirteen uterine tumors were diagnosed in 13 cats and accounted for 0.29% of all feline neoplasms received during a 9.6-year period. Age at diagnosis ranged from 3 to 16 years; median 9 years. Six were Domestic Shorthair cats, and 7 were purebred cats of 5 different breeds. Eight adenocarcinomas and 1 mixed Müllerian tumor (adenosarcoma) comprised the endometrial tumors. Myometrial tumors included 3 leiomyomas and 1 leiomyosarcoma. One of the adenocarcinomas developed in the uterine stump of an ovariohysterectomized cat; the other cats were sexually intact. Concurrent mammary adenocarcinoma was diagnosed in 1 cat with uterine adenocarcinoma and in another with uterine leiomyoma. Tumors were discovered during elective ovariohysterectomy in 2 cats, but at least 3 others had experienced reproductive problems (infertility or pyometra). Five cats presented for abdominal or pelvic masses. Endometrial adenocarcinomas were positive immunohistochemically for cytokeratins and negative for smooth muscle actin (SMA): 1 of 6 cats was positive for vimentin and 4 of 8 were positive for estrogen receptor-alpha (ER alpha). Adenosarcoma stromal cells were positive for vimentin and ER alpha but negative for cytokeratins and SMA. Smooth muscle tumors were positive for vimentin and SMA and negative for cytokeratins. Leiomyomas, but not the leiomyosarcomas, were positive for ER alpha. Adenocarcinomas in 4 cats had metastasized by the time of ovariohysterectomy. Two other cats were euthanized 5 months after ovariohysterectomy; at least one of these cats had developed an abdominal mass that was not examined histologically. Only 2 cats with endometrial adenocarcinoma had disease-free intervals longer than 5 months after surgery. Metastasis was not detected in any mesenchymal tumor; however, these cats were either euthanized on discovery of the tumor or the tumor was first detected at necropsy.     

A collision tumor consisting of granular cell tumor and adenocarcinoma in the uterus of an aged djungarian hamster

A neoplastic nodular lesion consisting of an admixture of granular cell tumor and adenocarcinoma was found in the uterus of a 26-month-old Djungarian hamster. Neoplastic cells of the uterine adenocarcinoma showed an epithelial nature in their growth patterns and by cytokeratin-immunopositive reaction, exhibiting nuclear pleomorphism. The granular cells had an abundant amount of fine granular eosinophilic cytoplasm and eccentric or central nuclei with no nuclear atypia; the granular structures were positive for periodic acid-Schiff with diastase resistance and were confirmed as lysosomes/autophagosomes by electron microscopy; immunohistochemically, the cells reacted to desmin, vimentin and α-smooth muscle actin and negatively for neurogenic, histiocyte/macrophage or epithelial markers, indicating smooth muscle origin. Because these tumors were generated from different cell origins, a diagnosis of collision tumor was made.