Ex) Article Title, Author, Keywords
pISSN 1598-298X
eISSN 2384-0749
Ex) Article Title, Author, Keywords
J Vet Clin 2024; 41(1): 18-23
https://doi.org/10.17555/jvc.2024.41.1.18
Published online February 28, 2024
Tae-Hyung Kwon , Guk-Il Jung
, Kun-Ho Song
, Joong-Hyun Song*
Correspondence to:*jh.song@cnu.ac.kr
Copyright © The Korean Society of Veterinary Clinics.
A 13-year-old spayed female Golden Retriever with clinical signs of weight loss and lethargy presented with two esophageal masses and one sessile polyp on computed tomography and esophagoscopy. Endoscopic snare resection was performed, and histopathological examination was requested. Based on histopathology and immunohistochemistry of multiple myeloma oncogene 1 staining, the patient was diagnosed with esophageal extramedullary plasmacytoma. The patient remained clinically well without any clinical signs during a follow-up period of 12 months. Herein, we report the successful diagnosis and management of esophageal extramedullary plasmacytoma in a dog using endoscopy.
Keywords: endoscopy, esophageal tumor, immunohistochemistry, monoclonal plasmacytic tumor
Extramedullary plasmacytoma (EMP) is a solitary collection of monoclonal plasmacytic tumors originating from the soft tissues (24). The most common locations for EMP in dogs are the cutaneous sites of the limbs and head, mucous membranes of the oral cavity and lips, and the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, and large intestine (24). EMP arising in the esophagus is extremely rare, with only one case having been reported in veterinary medicine and six in human medicine (9,12). Typically, cutaneous and oral EMPs in dogs are benign and respond well to local therapy. However, EMPs in the GI tract have been reported to exhibit different metastatic behaviors depending on their location (2,24). Colorectal EMP typically has a benign behavior, but gastric EMP has been reported to behave aggressively with frequent nodal metastasis (2,24). However, the clinical features of esophageal EMP are unknown because of its low incidence (9,24).
The diagnosis of EMP usually requires tissue biopsy, histopathological evaluation, and immunohistochemistry (IHC) (24). Immunohistochemical studies directed at detecting immunoglobulin light and heavy chains, thioflavin-T, or multiple myeloma 1 (MUM1) are helpful in differentiating plasmacytomas from other round cell tumors and in the definitive diagnosis of plasmacytomas (17,24). In veterinary medicine, there are no treatment guidelines for esophageal plasmacytoma; however, surgical management, chemotherapy, radiation therapy, and endoscopic management have been proposed in humans medicine (1,6,8,12,15,16,19,25).
A 13-year-old spayed female Golden Retriever was referred to the Veterinary Medical Teaching Hospital of the Chungnam National University. The patient presented with weight loss, anorexia, and recurrent oral acanthomatous ameloblastoma. Computed tomography (CT) for screening the invasiveness of the acanthomatous ameloblastoma incidentally revealed masses in the esophagus.
On physical examination, the enlarged right submandibular and left prescapular lymph nodes were palpated, measuring 27 × 13 mm and 18 × 20 mm, respectively. Fine-needle aspiration was performed on these lymph nodes and no microscopic findings of malignancy or metastasis were confirmed. There were no other remarkable findings on the physical examination. Laboratory test results, including complete blood count (ProCyte Dx®, IDEXX, Portland, ME, USA), complete urine analysis (Vetlab UA Analyzer, IDEXX, Westbrook, USA), serum biochemistry (Catalyst One, IDEXX, Westbrook, USA), and blood gas analysis (pHOx Ultra Blood Gas Analyzer, Nova Biomedical, USA) were within normal reference ranges. On thoracic and abdominal radiographs, the enlarged left prescapular lymph node was found, measuring 23 mm × 9 mm, and there was no evidence of osteolytic bone abnormalities, except the incisive part of the mandibular acanthomatous ameloblastoma lesion. On CT scanning (Alexion TM, Canon Medical Systems, Japan), two esophageal masses were found at the level of the 7th cervical spine and 2nd thoracic spine of the esophageal lumen, measuring 2.8 cm × 1.2 cm and 1.6 cm × 0.7 cm, respectively (Fig. 1). Flexible esophagoscopy revealed two large round protruding esophageal masses with a multinodular appearance, prominent submucosal blood vessels, and one sessile polyp with a normal-appearing mucosa (Fig. 2). During the procedure, two masses and one sessile polyp were resected using an endoscopic snare.
Resected esophageal masses were sent to a commercial laboratory (IDEXX Laboratories, Inc., USA). Histopathologically, cells with distinct borders, moderate amounts of eosinophilic cytoplasm, and intracytoplasmic eosinophilic globules were observed. In addition, anisocytosis and anisokaryosis were moderate, with occasional binucleated and multinucleated cells, consistent with esophageal plasmacytoma. On immunohistochemistry, round cells have strong intranuclear staining and immunoreactivity for multiple myeloma oncogene 1 (MUM1) (Fig. 3). On the basis of these results, the patient was definitively diagnosed with esophageal EMP.
In this patient, additional systemic chemotherapy with melphalan and prednisolone was planned after endoscopic resection of the tumor; however, the client refused further treatment. Without additional treatment, the patient remained clinically well without any clinical signs until a follow-up period of 12 months.
Esophageal EMP in dogs were first diagnosed by Hamilton and Carpenter (9) in 1994. There were commonalities and differences between the macroscopic features of the tumors in the initial article and the present case report (9). In a previous case report, the mass was large, ulcerated, hemorrhagic, and multinodular in appearance (9). In contrast, the masses in this case had a nodular appearance with prominent submucosal blood vessels without ulceration and hemorrhage, which protruded toward the esophageal lumen; one EMP caudal to the 2nd mass was a sessile polyp with a normal mucosal layer. Canine esophageal tumors usually present as protruding proliferative masses, and malignant tumors typically exhibit a mucosal surface that is more ulcerated and lobulated (21). The tumor morphology in the initial report had several similarities to that of a typical malignant esophageal tumor (9,21). In contrast, in this case, a normal mucosal layer was observed and the mass presented as a polyp. Thus, given the macroscopic features of the esophageal EMP observed in this case, the specific tumor type or metastatic behavior cannot be predicted by macroscopic examination alone. Hence, endoscopic resection followed by histopathological evaluation is recommended for precise tumor differentiation, even in the absence of clinical symptoms.
The diagnosis of GI EMP, including that of the esophagus, is based on cytology and endoscopic evaluation of the GI tract (24). While EMP tends to have distinct histopathologic features, such as cells with a pink periphery suggestive of a flame cell, intracytoplasmic Russell bodies (Mott cell), or amorphous eosinophilic material (e.g., amyloid), it is possible that some EMP represent histopathologic features of other round cell neoplasms (18). In such cases, the application of immunohistochemical immunoreactivity can facilitate the diagnosis of GI EMP (2-5,9,13,14,23,24). Among the IHC panels used for diagnosing canine EMP, MUM1 is a transcription factor that plays a key role in plasma cell production and is a specific and sensitive marker of EMP (17). However, some B cell lymphomas are labeled with MUM1 depending on their direction of differentiation (17). In a study on the IHC features of EMP in dogs, 101 out of 109 EMP (92.7%) were immunoreactive for MUM1 (17). In the same study, all B-cell lymphomas were immunopositive for B-cell markers, including CD20 and CD79a; however, 10 of 47 B-cell lymphomas (21.2%) were also immunoreactive for MUM1 (17). Although MUM1 is highly specific for canine plasmacytomas among the various IHC markers, diagnosis should rely on a combined assessment of histopathological and IHC features, as IHC results alone may not definitively differentiate between EMP and B-cell lymphoma in dogs (17).
Depending on the esophageal tumor type, treatment options including surgery, chemotherapy, and radiation therapy can be considered (24). For the treatment of esophageal tumors, resection with a complete surgical margin is the preferred approach (24). However, there are no treatment guidelines for esophageal EMP in dogs because of their rare incidence (9). In cases of EMP in other organs of the GI tract, including the stomach and rectum, those who underwent surgical excision with complete surgical margins did not experience recurrence (5,13). In the first reported case of esophageal EMP, the segment of the esophagus invaded by the tumor was surgically resected, and the patient was clinically well during a follow-up period of eighteen months (9).
However, esophageal surgery has historically been associated with a higher prevalence of incisional dehiscence than surgery in other portions of the alimentary tract due to several factors, including the lack of serosa, segmental nature of the blood supply, lack of omentum, constant motion caused by swallowing and respiration, and tension at the surgical site (11). According to a study on the complications of esophageal surgery, eight out of 63 dogs (13%) had intraoperative complications such as hemorrhage, hypotension, or hypertension, and 23 out of 63 dogs (37%) experienced postoperative complications such as aspiration pneumonia or respiratory distress (20). In our case, the three esophageal tumors were located in various locations within the esophagus. Furthermore, given the possibility of complications from extensive surgical excision at multiple sites, endoscopic resection was considered.
In previous case studies, two dogs with EMPs in the stomach underwent systemic chemotherapy with melphalan and prednisolone as sole treatments (2,14). One case showed no recurrence after complete remission, while the other case revealed resolution of the gastric mass and marked size reduction of associated lymph nodes for 3 months but progressive disease after 6 months (2,14). However, in two other case studies of one dog with colonic EMP and one dog with rectal EMP who underwent surgical excision with systemic chemotherapy, no recurrence was reported, the dogs lived until the follow-up period of 9 and 22 months, respectively (14,23). Considering these case reports, although systemic chemotherapy alone seems to be effective against EMP, a combination of surgery and chemotherapy is considered a more effective treatment option for GI EMP (2,14,23).
Esophageal EMP is rare in humans. To the best of our knowledge, only eight cases have been reported, and only five cases in which both diagnosis, treatment, and follow-up have been conducted. Among these five patients who underwent follow-up, one underwent local resection and cyclophosphamide chemotherapy, two underwent esophagogastrectomy, one underwent endoscopic submucosal dissection (ESD), and one underwent radiation therapy. These patients had no recurrence during a median follow-up period of 6 months (range: 5 days to 30 months) (1,6,8,12,15,16,19,25). Although there are no established treatment protocols, owing to the limited number of case reports, considering the positive outcomes in all locally treated human cases, esophageal EMP is suspected to have low local aggression, and local resection with or without adjunctive chemotherapy should be curative; these treatment options could also be considered in veterinary practice.
Endoscopic techniques used for resecting esophageal EMP have advantages, including direct tumor visualization and reduced invasiveness, such as endoscopic mucosal resection (EMR) and ESD (10,22). EMR and ESD are advanced, minimally invasive procedures for the endoscopic removal of polyps or masses from the GI tract. EMR requires a snare to remove polyps or masses < 2 cm, while ESD using an electrosurgical knife is utilized to remove larger masses that are not amenable to EMR. (10,22). Both techniques involve submucosal injection of saline to lift the tumor, enabling complete endoscopic margin resection. However, both methods are associated with risks including bleeding, pain, puncture of the digestive tract, and scarring, which can lead to esophageal narrowing (7,10,22). Most studies in the current veterinary literature are focused solely on experimental models for safety assessment (10,22). In situations where the morphological features of tumors are not amenable to ESD or EMR or the equipment is unavailable, proceeding with endoscopic snare resection is advisable. After the procedure, the patient displayed no clinical signs; therefore, further treatment was not required.
In conclusion, esophageal EMP can have various morphological features, and clinicians should consider esophageal EMP as a differential diagnosis for esophageal tumors. To the best of our knowledge, this is the second canine case of esophageal EMP that was successfully diagnosed endoscopically and the first to be managed by endoscopic resection. Therefore, this study may aid in the diagnosis and treatment of esophageal EMP in veterinary medicine. For the successful diagnosis of esophageal EMP, our case report emphasizes the importance of not only CT scanning and endoscopic evaluation of the esophagus, but also histopathological and immunohistochemical evaluation of the esophageal tumor. Furthermore, when endoscopic resection is feasible, it may be a good treatment option for esophageal EMP.
This study was supported by the National Research Foundation of Korea and was funded by a grant from the Korean Government (NRF-2022R1G1A10036821131482092640101).
The authors have no conflicting interests.
J Vet Clin 2024; 41(1): 18-23
Published online February 28, 2024 https://doi.org/10.17555/jvc.2024.41.1.18
Copyright © The Korean Society of Veterinary Clinics.
Tae-Hyung Kwon , Guk-Il Jung
, Kun-Ho Song
, Joong-Hyun Song*
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, South Korea
Correspondence to:*jh.song@cnu.ac.kr
This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
A 13-year-old spayed female Golden Retriever with clinical signs of weight loss and lethargy presented with two esophageal masses and one sessile polyp on computed tomography and esophagoscopy. Endoscopic snare resection was performed, and histopathological examination was requested. Based on histopathology and immunohistochemistry of multiple myeloma oncogene 1 staining, the patient was diagnosed with esophageal extramedullary plasmacytoma. The patient remained clinically well without any clinical signs during a follow-up period of 12 months. Herein, we report the successful diagnosis and management of esophageal extramedullary plasmacytoma in a dog using endoscopy.
Keywords: endoscopy, esophageal tumor, immunohistochemistry, monoclonal plasmacytic tumor
Extramedullary plasmacytoma (EMP) is a solitary collection of monoclonal plasmacytic tumors originating from the soft tissues (24). The most common locations for EMP in dogs are the cutaneous sites of the limbs and head, mucous membranes of the oral cavity and lips, and the gastrointestinal (GI) tract, including the esophagus, stomach, small intestine, and large intestine (24). EMP arising in the esophagus is extremely rare, with only one case having been reported in veterinary medicine and six in human medicine (9,12). Typically, cutaneous and oral EMPs in dogs are benign and respond well to local therapy. However, EMPs in the GI tract have been reported to exhibit different metastatic behaviors depending on their location (2,24). Colorectal EMP typically has a benign behavior, but gastric EMP has been reported to behave aggressively with frequent nodal metastasis (2,24). However, the clinical features of esophageal EMP are unknown because of its low incidence (9,24).
The diagnosis of EMP usually requires tissue biopsy, histopathological evaluation, and immunohistochemistry (IHC) (24). Immunohistochemical studies directed at detecting immunoglobulin light and heavy chains, thioflavin-T, or multiple myeloma 1 (MUM1) are helpful in differentiating plasmacytomas from other round cell tumors and in the definitive diagnosis of plasmacytomas (17,24). In veterinary medicine, there are no treatment guidelines for esophageal plasmacytoma; however, surgical management, chemotherapy, radiation therapy, and endoscopic management have been proposed in humans medicine (1,6,8,12,15,16,19,25).
A 13-year-old spayed female Golden Retriever was referred to the Veterinary Medical Teaching Hospital of the Chungnam National University. The patient presented with weight loss, anorexia, and recurrent oral acanthomatous ameloblastoma. Computed tomography (CT) for screening the invasiveness of the acanthomatous ameloblastoma incidentally revealed masses in the esophagus.
On physical examination, the enlarged right submandibular and left prescapular lymph nodes were palpated, measuring 27 × 13 mm and 18 × 20 mm, respectively. Fine-needle aspiration was performed on these lymph nodes and no microscopic findings of malignancy or metastasis were confirmed. There were no other remarkable findings on the physical examination. Laboratory test results, including complete blood count (ProCyte Dx®, IDEXX, Portland, ME, USA), complete urine analysis (Vetlab UA Analyzer, IDEXX, Westbrook, USA), serum biochemistry (Catalyst One, IDEXX, Westbrook, USA), and blood gas analysis (pHOx Ultra Blood Gas Analyzer, Nova Biomedical, USA) were within normal reference ranges. On thoracic and abdominal radiographs, the enlarged left prescapular lymph node was found, measuring 23 mm × 9 mm, and there was no evidence of osteolytic bone abnormalities, except the incisive part of the mandibular acanthomatous ameloblastoma lesion. On CT scanning (Alexion TM, Canon Medical Systems, Japan), two esophageal masses were found at the level of the 7th cervical spine and 2nd thoracic spine of the esophageal lumen, measuring 2.8 cm × 1.2 cm and 1.6 cm × 0.7 cm, respectively (Fig. 1). Flexible esophagoscopy revealed two large round protruding esophageal masses with a multinodular appearance, prominent submucosal blood vessels, and one sessile polyp with a normal-appearing mucosa (Fig. 2). During the procedure, two masses and one sessile polyp were resected using an endoscopic snare.
Resected esophageal masses were sent to a commercial laboratory (IDEXX Laboratories, Inc., USA). Histopathologically, cells with distinct borders, moderate amounts of eosinophilic cytoplasm, and intracytoplasmic eosinophilic globules were observed. In addition, anisocytosis and anisokaryosis were moderate, with occasional binucleated and multinucleated cells, consistent with esophageal plasmacytoma. On immunohistochemistry, round cells have strong intranuclear staining and immunoreactivity for multiple myeloma oncogene 1 (MUM1) (Fig. 3). On the basis of these results, the patient was definitively diagnosed with esophageal EMP.
In this patient, additional systemic chemotherapy with melphalan and prednisolone was planned after endoscopic resection of the tumor; however, the client refused further treatment. Without additional treatment, the patient remained clinically well without any clinical signs until a follow-up period of 12 months.
Esophageal EMP in dogs were first diagnosed by Hamilton and Carpenter (9) in 1994. There were commonalities and differences between the macroscopic features of the tumors in the initial article and the present case report (9). In a previous case report, the mass was large, ulcerated, hemorrhagic, and multinodular in appearance (9). In contrast, the masses in this case had a nodular appearance with prominent submucosal blood vessels without ulceration and hemorrhage, which protruded toward the esophageal lumen; one EMP caudal to the 2nd mass was a sessile polyp with a normal mucosal layer. Canine esophageal tumors usually present as protruding proliferative masses, and malignant tumors typically exhibit a mucosal surface that is more ulcerated and lobulated (21). The tumor morphology in the initial report had several similarities to that of a typical malignant esophageal tumor (9,21). In contrast, in this case, a normal mucosal layer was observed and the mass presented as a polyp. Thus, given the macroscopic features of the esophageal EMP observed in this case, the specific tumor type or metastatic behavior cannot be predicted by macroscopic examination alone. Hence, endoscopic resection followed by histopathological evaluation is recommended for precise tumor differentiation, even in the absence of clinical symptoms.
The diagnosis of GI EMP, including that of the esophagus, is based on cytology and endoscopic evaluation of the GI tract (24). While EMP tends to have distinct histopathologic features, such as cells with a pink periphery suggestive of a flame cell, intracytoplasmic Russell bodies (Mott cell), or amorphous eosinophilic material (e.g., amyloid), it is possible that some EMP represent histopathologic features of other round cell neoplasms (18). In such cases, the application of immunohistochemical immunoreactivity can facilitate the diagnosis of GI EMP (2-5,9,13,14,23,24). Among the IHC panels used for diagnosing canine EMP, MUM1 is a transcription factor that plays a key role in plasma cell production and is a specific and sensitive marker of EMP (17). However, some B cell lymphomas are labeled with MUM1 depending on their direction of differentiation (17). In a study on the IHC features of EMP in dogs, 101 out of 109 EMP (92.7%) were immunoreactive for MUM1 (17). In the same study, all B-cell lymphomas were immunopositive for B-cell markers, including CD20 and CD79a; however, 10 of 47 B-cell lymphomas (21.2%) were also immunoreactive for MUM1 (17). Although MUM1 is highly specific for canine plasmacytomas among the various IHC markers, diagnosis should rely on a combined assessment of histopathological and IHC features, as IHC results alone may not definitively differentiate between EMP and B-cell lymphoma in dogs (17).
Depending on the esophageal tumor type, treatment options including surgery, chemotherapy, and radiation therapy can be considered (24). For the treatment of esophageal tumors, resection with a complete surgical margin is the preferred approach (24). However, there are no treatment guidelines for esophageal EMP in dogs because of their rare incidence (9). In cases of EMP in other organs of the GI tract, including the stomach and rectum, those who underwent surgical excision with complete surgical margins did not experience recurrence (5,13). In the first reported case of esophageal EMP, the segment of the esophagus invaded by the tumor was surgically resected, and the patient was clinically well during a follow-up period of eighteen months (9).
However, esophageal surgery has historically been associated with a higher prevalence of incisional dehiscence than surgery in other portions of the alimentary tract due to several factors, including the lack of serosa, segmental nature of the blood supply, lack of omentum, constant motion caused by swallowing and respiration, and tension at the surgical site (11). According to a study on the complications of esophageal surgery, eight out of 63 dogs (13%) had intraoperative complications such as hemorrhage, hypotension, or hypertension, and 23 out of 63 dogs (37%) experienced postoperative complications such as aspiration pneumonia or respiratory distress (20). In our case, the three esophageal tumors were located in various locations within the esophagus. Furthermore, given the possibility of complications from extensive surgical excision at multiple sites, endoscopic resection was considered.
In previous case studies, two dogs with EMPs in the stomach underwent systemic chemotherapy with melphalan and prednisolone as sole treatments (2,14). One case showed no recurrence after complete remission, while the other case revealed resolution of the gastric mass and marked size reduction of associated lymph nodes for 3 months but progressive disease after 6 months (2,14). However, in two other case studies of one dog with colonic EMP and one dog with rectal EMP who underwent surgical excision with systemic chemotherapy, no recurrence was reported, the dogs lived until the follow-up period of 9 and 22 months, respectively (14,23). Considering these case reports, although systemic chemotherapy alone seems to be effective against EMP, a combination of surgery and chemotherapy is considered a more effective treatment option for GI EMP (2,14,23).
Esophageal EMP is rare in humans. To the best of our knowledge, only eight cases have been reported, and only five cases in which both diagnosis, treatment, and follow-up have been conducted. Among these five patients who underwent follow-up, one underwent local resection and cyclophosphamide chemotherapy, two underwent esophagogastrectomy, one underwent endoscopic submucosal dissection (ESD), and one underwent radiation therapy. These patients had no recurrence during a median follow-up period of 6 months (range: 5 days to 30 months) (1,6,8,12,15,16,19,25). Although there are no established treatment protocols, owing to the limited number of case reports, considering the positive outcomes in all locally treated human cases, esophageal EMP is suspected to have low local aggression, and local resection with or without adjunctive chemotherapy should be curative; these treatment options could also be considered in veterinary practice.
Endoscopic techniques used for resecting esophageal EMP have advantages, including direct tumor visualization and reduced invasiveness, such as endoscopic mucosal resection (EMR) and ESD (10,22). EMR and ESD are advanced, minimally invasive procedures for the endoscopic removal of polyps or masses from the GI tract. EMR requires a snare to remove polyps or masses < 2 cm, while ESD using an electrosurgical knife is utilized to remove larger masses that are not amenable to EMR. (10,22). Both techniques involve submucosal injection of saline to lift the tumor, enabling complete endoscopic margin resection. However, both methods are associated with risks including bleeding, pain, puncture of the digestive tract, and scarring, which can lead to esophageal narrowing (7,10,22). Most studies in the current veterinary literature are focused solely on experimental models for safety assessment (10,22). In situations where the morphological features of tumors are not amenable to ESD or EMR or the equipment is unavailable, proceeding with endoscopic snare resection is advisable. After the procedure, the patient displayed no clinical signs; therefore, further treatment was not required.
In conclusion, esophageal EMP can have various morphological features, and clinicians should consider esophageal EMP as a differential diagnosis for esophageal tumors. To the best of our knowledge, this is the second canine case of esophageal EMP that was successfully diagnosed endoscopically and the first to be managed by endoscopic resection. Therefore, this study may aid in the diagnosis and treatment of esophageal EMP in veterinary medicine. For the successful diagnosis of esophageal EMP, our case report emphasizes the importance of not only CT scanning and endoscopic evaluation of the esophagus, but also histopathological and immunohistochemical evaluation of the esophageal tumor. Furthermore, when endoscopic resection is feasible, it may be a good treatment option for esophageal EMP.
This study was supported by the National Research Foundation of Korea and was funded by a grant from the Korean Government (NRF-2022R1G1A10036821131482092640101).
The authors have no conflicting interests.