Abstract
A 6-year-old, intact male Jack Russell terrier was diagnosed with a mass in the caudal abdomen, and ultrasound revealed a large prostatic mass. A total-body computed tomography scan was performed for staging, and lung nodules were detected. Histological examination showed a proliferation of spindle cells arranged in interlacing fascicles. Immunohistochemical staining revealed cells were cytokeratin negative and immunoreactive for vimentin and α-smooth muscle actin; cells stained with desmin and S-100 were negative. A diagnosis of primary prostatic leiomyosarcoma with pulmonary metastases was made. This is one of the rare cases of primary prostatic mesenchymal tumor in the canine species.
Introduction
Primary neoplasms of the prostate gland are uncommon in canine species and mostly arise from the glandular epithelium, with adenocarcinoma being the most frequently diagnosed tumor type.1 Sarcomas of the prostate are extremely rare in humans and animals.2–4 In humans, prostatic sarcoma represents <0.1% of all malignant tumors.2 In the dog, a single case of prostatic leiomyosarcoma and two cases of hemangiosarcoma have been documented.5–7 Prostatic diseases are most common in old, intact male dogs, and a progressive increase in the incidence of prostatic abnormalities is associated with advanced age.1,3 In this report, a case of primary prostatic leiomyosarcoma is described.
Case Report
A 6-year-old, intact male Jack Russell terrier with a 6-month history of stranguria and dyschezia was presented for a second opinion. Four months prior to the clinical examination, the dog was treated elsewhere for prostatic cysts by multiple sessions of drainage and alcoholization of the cystic cavities. Physical examination revealed a distended urinary bladder and a palpable mass in the caudal abdomen.
A complete blood count, serum biochemical profile, and urinalysis were normal. Ultrasound of the abdomen with an 8-MHz microconvex probea revealed a large, heterogenous mass in the prostate. A hyperechoic area was surrounded by a hypoechoic band in the cranioventral part of the prostate [Figure 1⇓]. Two large cysts were also present. Power Doppler was performed to assess vascularity of the tumor. Vascularity in the hyperechoic area was revealed, while no vessels were detected in the hypoechoic peripheric tissue. An ultrasound contrast study was performed using a second-generation contrast medium (0.03 mL/kg) with a linear 7.5-MHz probe.b A cranioventral area about 3 cm in diameter was always hypoechoic (during the wash-in, peak, and wash-out phases) compared to the surrounding tissues. Only a large feeding vessel was detected in that area.
Ultrasound image of the cranioventral part of the prostate (transverse view with power Doppler) of a 6-year-old, intact male Jack Russell terrier presented for stranguria and dyschezia. The prostate is heterogeneous with a central hyperechoic and vascularized zone and a hypoechoic ventral part approximately 3 × 1 cm (major diameters are shown) with no vascularity. V=ventral; D=dorsal; RT=right; LT=left.
The dog was anesthetized with intravenous diazepam and propofol and maintained with isoflurane. A helical total-body computed tomography (CT) scanc was performed for staging of the possible neoplasia. The dog was placed in dorsal recumbency, and CT imaging was done with 120 kV and 160 mA for 1 second using 5-mm slice thickness and pitch 1. Computed tomography images were made before and after the manual intravenous injection (800 mg/kg) of nonionic iodinated contrast medium.d Computed tomography revealed a large, heterogenous, and irregularly shaped prostate with two large cysts occupying the pelvic area [Figure 2⇓]. The contrast enhancement of the prostate was markedly heterogenous, with no contrast in the two cystic lesions; the contrast enhancement of the prostatic mass was mild. Several round nodules, consistent with metastases, were seen in the lungs [Figure 3⇓]. Ultrasound-guided Tru-Cut biopsy of the prostatic mass was performed with a 16-gauge spring-loaded needle. Histological examination of the biopsy revealed a poorly differentiated, neoplastic malignant spindle cell lesion of uncertain origin.
Computed tomography of the prostate after intravenous injection of non-ionic iodinated contrast medium; soft tissue window. The prostatic margins are defined by the dotted line. Dorsally the gland is occupied by two oval hypodense cysts (C) surrounded by thin, enhancing prostatic tissue. A large, ill-defined, and heterogeneous lesion is visible ventrally (L). The descending colon (CL) is displaced to the right. V=ventral; D=dorsal; RT=right; LT left.
Computed tomography of the thorax; lung window. A 4-mm, large nodule is visible in the left caudal lung lobe (arrow). CV=caudal caval vein; H=heart.
Because of a poor prognosis, the dog was euthanized. At necropsy, the prostate gland was completely replaced by a 7-cm diameter, poorly demarcated, whitish, firm mass. Transverse section of the prostate revealed a firm tissue with large, cystic, fluid-filled cavities. The tumor completely encircled the urethra, and the urinary bladder was distended and had a markedly thickened wall. Multiple, randomly distributed, 0.5-cm, white nodules were observed in the lungs.
Tissues for light microscopy were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned (4 μm thick), and stained with hematoxylin and eosin. Other sections were prepared for immunohistochemical analysis using an avidin-biotin complex method. Antibodies used were the following: cytokeratin AE1/AE3 (1:100 dilution, monoclonal),e vimentin (1:100 dilution, monoclonal),f α-smooth muscle actin (α-SMA), clone 1A4 (1:100 dilution, monoclonal),g desmin (1:100 dilution, monoclonal),h and S-100 (1:200 dilution).i Citric acid buffer-based microwave antigen retrieval was performed. Diaminobenzidinej was used as chromogen. Finally, the slides were counterstained with Papanicolau hematoxylin, dehydrated, and mounted under DPX.k The positive controls for each run consisted of one section from a tissue known to express the antigen being investigated. As a negative control for nonspecific binding, the primary antibody was replaced with an irrelevant, isotype-matched antibody.
Histopathological evaluation was performed on the prostate mass removed at necropsy. The prostate gland was expanded by an unencapsulated, poorly demarcated, infiltrative, highly cellular neoplasm composed of interlacing streams and bundles of neoplastic spindle cells within an abundantly extracellular, collagenous matrix. Neoplastic cells had indistinct cell borders and a moderate amount of eosinophilic cytoplasm frequently containing numerous, distinct, clear vacuoles. Nuclei were centrally located and elongated, with marginated chromatin and one to four distinct nucleoli. Marked anisocytosis and anisokaryosis were present. Mitotic figures were 15 per 10 high-power field (40 × objective) [Figure 4⇓]. Multiple foci of necrosis and small, multifocal areas of hemorrhage with a few hemosiderin-laden macrophages were present. Moreover, within the neoplasm, multiple follicular inflammatory foci (mostly composed of lymphocytes and lesser numbers of plasma cells and macrophages) were also visible. Occasionally spared, normal prostate gland that had become trapped in the tumor was visible. A diagnosis of high-grade (III) sarcoma was made based on a modified human grading system previously described by Kuntz et al.8 The lung nodules observed on gross postmortem examination had similar histology to the primary tumor and were located primarily within blood vessels.
Histopathology of the prostatic mass from Figures 1⇑ and 2⇑ removed at necropsy. The tumor consists of interlacing bundles of spindle cells with indistinct cell borders, elongated nuclei, and nuclear pleomorphism. A mitotic figure is visible (arrowhead). (Hematoxylin and eosin stain; bar=50 μm.)
Immunohistochemical analysis was performed for further characterization of the neoplasm. Cytoplasm from the majority of neoplastic cells stained intensely positive for vimentin [Figure 5A⇓]. Alpha-smooth muscle actin displayed strong cytoplasmic positive staining in approximately 50% of tumor cells [Figure 5B⇓]. Cytokeratin, desmin, and S-100 were not detected. A diagnosis of primary prostatic leiomyosarcoma was made based on positive staining for vimentin and α-SMA. Immunohistochemical analysis was not done on the histologically similar lung lesions.
Immunohistochemistry of the prostatic mass from Figures 1⇑, 2⇑, and 4⇑. (A) Brown staining indicates positive cytoplasmic immunoreactivity for vimentin. (B) The cytoplasm of neoplastic cells is strongly reactive for actin, indicating smooth muscle origin of the lesion. (DAB chromogen, Papanicolau’s counterstain; bar=50 μm.)
Discussion
A diagnosis of high-grade primary leiomyosarcoma with pulmonary metastases was made on the basis of spindle cell morphology, arrangement of tumor cells, positive staining of neoplastic cells for vimentin and α-SMA, and exclusion of other spindle cell tumors by negative results to a spectrum of immunohistochemical stains. The differential diagnoses for malignant spindle cell tumors of prostatic gland include fibrosarcoma, leiomyosarcoma, hemangiosarcoma, sarcomatoid carcinoma, malignant peripheral nerve sheath tumor (MPNST), liposarcoma, and myxosarcoma. Differentiating between these tumor types can sometimes be difficult.
Immunohistochemical analysis is helpful for the correct classification of mesenchymal tumors. In the present case, the mesenchymal origin of tumor cells was supported by strong cytoplasmic positivity to vimentin. Vimentin is a cytoplasmic intermediate filament that is expressed by a wide variety of mesenchymal tumors. The reaction to α-SMA and negative staining to desmin supported the diagnosis of leiomyosarcoma. Alpha-SMA and desmin are cytosolic intermediate filaments specific to smooth muscle cells and to skeletal muscle cells, respectively. Both are used in human and veterinary pathology to differentiate smooth and skeletal muscle tumors. Actin has been demonstrated in different types of tumors that display myofibroblastic differentiation. The actin antibody used in the present case (clone 1A4), however, specifically identifies actin isoforms found in smooth muscle.5 Moreover, negative staining for cytokeratin excluded the possibility of sarcomatoid carcinoma, and negative staining for S-100 excluded MPNST.
Prostatic sarcomas may arise from the mesenchymal stroma of the prostate, and the positivity to α-SMA may suggest an origin from the myofibroblastic stromal component. Some authors suggest that fibromuscular hyperplasia may give rise to both fibrosarcomas and leiomyosarcomas.2 In the case described here, the intimate relationship of the mass to the prostate, coupled with the histological appearance, supported an origin from the prostatic stromal tissue.
Diagnostic imaging is useful for the evaluation of the local extension of the tumor and the presence of distant metastases. Power Doppler and contrast ultrasound were performed to assess the vascularity and the perfusion of the mass, respectively; however, the findings were nonspecific. In the different phases of the tissue perfusion, contrast-enhanced ultrasound showed hypoechogenicity of the mass compared to surrounding tissue. In a recent study performed in splenic lesions, all malignancies showed different perfusion patterns compared to the surrounding parenchyma. After a variable wash-in phase, malignant tumors are hypoperfused in a wash-out phase. In contrast, benign lesions are characterized by similar perfusion to the adjacent parenchyma, so lesions are isoechoic at the peak and wash-out phases and no longer recognizable from the normal parenchyma.9 In the present case, the prostatic mass was always hypoechoic (during the wash-in, peak, and wash-out phases) compared to the surrounding tissue, similar to sarcomas described in the spleen.
Computed tomography is extremely useful for tumor staging, and in this case it allowed better evaluation of the extent of the lesion than ultrasound. Moreover, CT is more sensitive in examining for lung metastases than conventional radiology.10 Metastases of prostatic tumors are common in dogs and humans.1,2 The cases described in the literature of canine prostatic leiomyosarcoma and hemangiosarcoma metastasized to the lung;5–7 the course of these cases suggests that the prognosis for prostatic sarcomas can be very poor. In the present case, the tumor emboli within the vascular and lymphatic lumina of the pulmonary tissue was indicative of the cancer’s routes of metastasis.
Conclusion
This is a rare case of primary leiomyosarcoma of the prostate with pulmonary metastases in a dog.
Footnotes
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↵ a My-lab 30; Esaote, 50100 Firenze, Italy
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↵ b Sonovue; Bracco, 20100 Milano, Italy
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↵ c Pro-speed Power; General Electric, 20100 Milano, Italy
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↵ d Xenetix; Guerbet, 16100 Genova, Italy
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↵ e Cytokeratin AE1/AE3; Dako, 2600 Glostrup, Denmark
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↵ f Vimentin; Dako, 2600 Glostrup, Denmark
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↵ g Alpha-smooth muscle actin; Dako, 2600 Glostrup, Denmark
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↵ h Desmin; Dako, 2600 Glostrup, Denmark
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↵ i S-100; Dako, 2600 Glostrup, Denmark
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↵ j DAB; Sigma Chemical Company, St. Louis, MO 63108
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↵ k DPX; Fluka, Sigma-Aldrich Chemie GmbH, 9471 Buchs, Switzerland
