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Malignant hemangioendothelioma (angiosarcoma)
Malignant hemangioendothelioma (angiosarcoma) Judso~a J. Calhoun, D.D.S., Mesa, Ark
A
review of the available literature reveals that very little has been written regarding the tumor to be discussed in the present article. The consensus is that this tumor is rare and that malignant hemangioendotheliom is the name of choice. Ackerman? points out that Stout, for instance, collected only fourteen cases of soft-tissue malignant hemangioendothelioma. It seems to be accepted that this tumor may occur at any age. Thoma and Goldman3 describe two cases of angiosarcoma of the mandible (one in the first molar area reported by Blake and Blake in 1956 and another reported by Berger in 1942) and a case involving the maxilla of a 3-month-old child which was reported by Henny in 1949. The histopathologic picture is fairly well established. This tumor arises from the endothelial lining of the vessels, and it may grow in muscle, deep tissue, or periosteum. In an excellent article, Ramsey? points out the morphologic difference between hemangiopericytoma and hemangioendothelioma as viewed under the electron microscope. CASE REPORT When I first saw the patient in the hospital on Dec. 6, 1966, he was suffering from severe pain arising from the area of the lower right first molar. He was to have been seen the following morning for consultation, but when the severity of the pain made it impossible for him to sleep, he was seen at 1 A.M. The nurse on duty made note of a swelling on the right side of the mandible. Physical examination at this time revealed a Bl-year-old white man who appeared to be his stated age. He was in moderate to severe distress beoause of pain in the right mandible. There was an obvious swelling in the tissue overlying the mandible on the lateral aspect at the level of the first molar. This mass was tender to palpation and appeared to be somewhat Auctuant. There was a slight elevation of temperature. This mass also presented in the buccal sulcus, and there too there was an indication of fluctuation. There was also a slightly tender mass on the left side at the level of the third molar area. This mass was not as large, tender, or fluctuant as the one on the right. The patient, who was edentulous, was not aware of this
156
Volume Number
27 2
Malignant hemangioendothelioma
157
mass. There were no other significant findings intraorally. There were no palpable lymph nodes in the right or left side of the neck. There was some complaint of soreness in the area of the sternocleidomastoid muscle, but it appeared to be deep. The patient had been told that he had some cervical arthritis, and therefore this finding was dismissed. This man was hospitalized on the urologic service because of benign hypertrophic prostatic disease. Additional history revealed that the aforementioned mass in the mandibular area had been first noted by the patient on the day after Thanksgiving. He believed that this was merely a denture soreness and did not seek consultation. He stopped wearing the denture for 2 days, but this did not produce the desired relief. Because of his other problems, he did not pay any attention to the “sore in the mouth.” The mass did not increase appreciably in size, according to the patient, until 1 week prior to my seeing him. At that time, it began to enlarge to its present size, which was about that of a large pecan. The patient was not receiving any form of antibiotic therapy, so he was placed on a regimen of Combiotic, 2 C.C. intramuscularly twice a day, and 50 mg. Demerol intramuscularly every 4 hours as needed for pain. By the following afternoon he was much more comfortable, and there was less tenderness on each side of the mandible. On December 8 he underwent a transurethral resection, and a definitive diagnosis of “well-differentiated invasive adenocarcinoma of the prostate gland” was made. On December 12 an exploratory procedure was carried out on the mass on the right side of the mandible with the expectation that incision and drainage would be necessary. Preoperatively, there was a remote possibility of a metastatic lesion from the prostate as a secondary diagnosis. Procedure
At 1 P. M. on December 12 the patient was taken to the operating room, where he was anesthetized with Pentothal sodium, intubated nasally, and carried along on nitrous oxide, oxygen, and Fluothane. At this time, an intraoral examination revealed a fluctuant mass on the right side approximately opposite the right first molar area. It was thought that this might possibly represent a residual abscess formation. Therefore, an incision was made directly over the mass intraorally. It was noted that no pus was present but that there was a purplish mass just beneath the mucous membrane. By careful blunt and sharp dissection, the plane around the mass was established, and it was enucleated as completely as possible. It was also noted that there was some invasion of the bone, forming a possible osteolytic lesion. The inferior alveolar canal waa demonstrated at this point, and some of the bone was removed by means of rongeurs. The area was packed with Gelfoam and closed with 3-O black silk. An incision was then made over the mass on the left side. This time, by careful dissection, the mass was brought into view, and the planes of encapsulation were found. The lesion appeared to be more encapsulated and not attached to the bone; nor had it invaded the bone. There was some erosion of the bone, but it was smooth and no osteolytic process could be demonstrated. The mass was sent for frozen section, and the pathologist reported that this was a benign lesion. The area was then packed with Gelfoam and closed with 3-O black silk. The tissue from the right side was sent for routine examination. Following extubation, the patient was sent to the recovery room in excellent condition. A complete bone survey was performed on December 13, and no osteolytic lesions were found in any other bone of the body. Roentgenograms of the cervical spine, however, did show changes consistent with old rheumatoid arthritis, with some hypertrophic bridging between the last two cervical segments. On December 14 the pathologist informed us that this was undoubtedly an angiosarcoma of the mandible. It was thought that this could be a primary lesion even though it was bilateral. The pathologist was of the opinion that the left side was probably corn-
158
Calhoun
O.S., 0.x February,
& 0.1’. 1969
pletely enucleatecl but that the right side had not been completely rcnloved because of 1111: bone invasion noted at the time of surgical intervention. With this probability in mind, the case was presented to the Tumor Board at Memorial Hospital in Phoenix, Arizona, on December 16. It was recommended that the patient receive 0.5 mg. of actinompcin D intravenously every day for 5 days. Cobalt irradiation was to begin on the third day of actinomycin D treatment and was to be carried to tumor dose and/or toxicity. The lesion on the right side had grown until it was almost double its former size. On December 28 this treatment was begun on an inpatient basis at Memorial Hospital. The patient received actinomycin D and the cobalt therapy was begun on the third day. 11~ was discharged from the hospital on December 31, to follow the course of cobalt therapy as an outpatient. The lesion on the right side of the mandible responded very well to the cobalt therapy, as it melted almost completely away. There was some resulting breakdown of the incision, as well as some exposure of the bone. The lesion on the left had not recurred and, therefore, received no cobalt irradiation. During t.his time, the patient was experiencing some prostatic or urinary problems in His urologist had placed him on “hormone that he was having a constant hematuria. therapy” for the prostatic carcinoma at the time of the original discharge from the hospital. The patient seemed to be responding nicely am1 was improving on the cobalt and hormone therapy until Jan. 22, 1967. At that time he was readmitted to the Mesa Lutheran Hospital’s Orthopedic Service with severe pain beneath the right sternocleidomastoid muscle. He was placed in cervical traction, which had to be discontinued almost immediately because of a severe erythematous reaction to the face and neck due to the cobalt. There was slight improvement during the folIonTing week. He did, however, continue to receive the cobalt therapy at Memorial Hospital. On January 27 the case was re-presented to the Tumor Board. The Board thought there was a po’ssibility that an abscess was forming beneath the sternocleidomastoid muscle and that the patient should be given large doses of chloramphenicol and vigorous heat therapy. If there was no relief, a fasciotomy of that area should be considered. This treatment was instituted, and during the following week the pain subsided and the patient felt better. He was subsequently discharged from the hospital on February 3. On February 6 the patient was seen in our office as an outpatient. At this time, the neck pain was returning and he was placed on heat therapy but no antibiotics. Again the pain subsided. It was thought at this time that a mass was definitely palpable behind the sternocleidomastoid muscle. For this reason, the case was again presented to the Tumor Board, where the consensus was that a definite mass was present and that it was undoubtedly metastatic from the mandible. The patient was given another course of actinomycin D in the same dosage as before, and cobalt irradiation was again instituted on the third day. The rationale of the aetinomycin D is to sensitize the tumor to cobalt. The portal of cobalt irradiation was the right sternocleidomastoid muscle. The treatment was begun on February 3.3. There did not seem to be the marked improvement that had been hoped for or that had been seen the first time The patient followed a progressively downhill course, physically, and on February 17 it was thought that he was developing “Homer’s syndrome.” On February 20 the patient was readmitted to the Mesa Lutheran Hospital Medical Service. The admitting diagnosis was (1) angiosarcoma of the mandible with metastatic lesions and (2) moderate to severe debilitation. A Foley catheter was inserted, and it was noted that there was free blood in the urine. On admission, the bilirubin was slightly elevated. Platelets were somewhat depressed to 110,000; the white count was elevated-16,256, with 80 segmented leukocytes, 4 bands, 12 lymphocytes, and 4 eosinophils. There were no other significant laboratory findings. Physical examination at that time showed an elderly, obviously ill man who responded sluggishly to questioning. The blood pressure was 132/78;
Volume Number
27 2
Malignant
hemangioendothelioma
159
temperature, 102” F.; and pulse, 128. The weight was 169 pounds. The patient was pale. Marked moist riles were present in the upper right and midlung fields. Atria1 fibrillation was present, with murmurs of mitral insufficiency. Abdominal examination did not reveal any masses or tenderness. The hospital course was downhill, and the patient died on February 21. A postmortem examination was performed on February 22. Autopsy
findings
Grossly, there was a purplish, gelatinous type of tumor in the region of the adrenal glands, consistent with the angiosarcoma found originally in the mandible. The bladder was full of the same type of tumor formation. When the heart was opened, a similar mass was found in the atria1 septum. There was also tumor formation beneath 6he right sternocleidomastoid muscle, but this showed some signs of having been treated and looked as though it were regressing. It did not have the same malignant appearance. The diagnosis of angiosarcoma of the aforementioned organs was subsequently confirmed by means of microscopic sections.
DISCUSSION It has been shown that the occurrence of angiosarcoma or malignant hemangioendothelioma is very rare. There is little dissent in the literature regarding the eventual outcome of an advanced case of angiosarcoma. Also, there is little argument that it is an extremely malignant and fast-growing tumor. Most histopathologists agree that t,his type of tumor arises from the endothelial lining of the vascular tree. It is recognized that there is little organization of the tumor cells and that they may even completely obliterate the vascular channels. Recently, through electron microscopy, the characteristic silver reticulin staining has been found to be due to the condensation into strata of the fine fibrillar and flocculent extracellular material. In the case presented here, we have shown a bilateral angiosarcoma in the area of the mandible and involving the bone on the right side. It has also been shown that this was probably a metastatic lesion from the heart; however, this is only conjecture. It is not likely that the tumor of the mandible was of primary origin, since the lesion was bilateral, with the primary origin probably in the heart. This case tends to point out more strongly the malignancy of this tumor and the extreme rapidity of its growth. It is interesting to note the tumor’s strange proclivity for certain organs. As was mentioned in the opening portion of this article, the tumor has been found in kidney, skin, bone, heart, and lungs. In this case, all but the skin and lungs were involved. SUMMARY In retrospect, in view of the negative bone survey and also the pain beneath the right sternocleidomastoid muscle, it seems that one should have considered the possibility of a metastatic lesion from some internal soft-tissue organ, the heart being the most likely. It is also possible that, through some form of angiography, a diagnosis could have been made, thereby permitting treatment with actinomycin D and local cobalt irradiation to the heart. This case also helps to point up the fact that this tumor is difficult to diagnose and that it has the ability to mimic other much less malignant diseases.
160
Calhom
03, ox. .Februarp,
& 0.1’. 1969
REFERENCES
1. Ackerman, Lauren V.: Surgical Pathology, ed. 2, St. Louis, 1959, The C:. 1’. JIosby Cumpany, p. 855. 2. Ramsey, Helen J.: Fine Structures of Hemangiopericytoma and Hemangio-endothelioma, Cancer 19: 2005-2017, 1966. 3. Thoma, K. H., and Goldman, H. M.: Oral Pathology, ed. 5, St. Louis, 1960, The C. V. Mosby Company, p. 1399. 431 West 5th PI.
A
review of the available literature reveals that very little has been written regarding the tumor to be discussed in the present article. The consensus is that this tumor is rare and that malignant hemangioendotheliom is the name of choice. Ackerman? points out that Stout, for instance, collected only fourteen cases of soft-tissue malignant hemangioendothelioma. It seems to be accepted that this tumor may occur at any age. Thoma and Goldman3 describe two cases of angiosarcoma of the mandible (one in the first molar area reported by Blake and Blake in 1956 and another reported by Berger in 1942) and a case involving the maxilla of a 3-month-old child which was reported by Henny in 1949. The histopathologic picture is fairly well established. This tumor arises from the endothelial lining of the vessels, and it may grow in muscle, deep tissue, or periosteum. In an excellent article, Ramsey? points out the morphologic difference between hemangiopericytoma and hemangioendothelioma as viewed under the electron microscope. CASE REPORT When I first saw the patient in the hospital on Dec. 6, 1966, he was suffering from severe pain arising from the area of the lower right first molar. He was to have been seen the following morning for consultation, but when the severity of the pain made it impossible for him to sleep, he was seen at 1 A.M. The nurse on duty made note of a swelling on the right side of the mandible. Physical examination at this time revealed a Bl-year-old white man who appeared to be his stated age. He was in moderate to severe distress beoause of pain in the right mandible. There was an obvious swelling in the tissue overlying the mandible on the lateral aspect at the level of the first molar. This mass was tender to palpation and appeared to be somewhat Auctuant. There was a slight elevation of temperature. This mass also presented in the buccal sulcus, and there too there was an indication of fluctuation. There was also a slightly tender mass on the left side at the level of the third molar area. This mass was not as large, tender, or fluctuant as the one on the right. The patient, who was edentulous, was not aware of this
156
Volume Number
27 2
Malignant hemangioendothelioma
157
mass. There were no other significant findings intraorally. There were no palpable lymph nodes in the right or left side of the neck. There was some complaint of soreness in the area of the sternocleidomastoid muscle, but it appeared to be deep. The patient had been told that he had some cervical arthritis, and therefore this finding was dismissed. This man was hospitalized on the urologic service because of benign hypertrophic prostatic disease. Additional history revealed that the aforementioned mass in the mandibular area had been first noted by the patient on the day after Thanksgiving. He believed that this was merely a denture soreness and did not seek consultation. He stopped wearing the denture for 2 days, but this did not produce the desired relief. Because of his other problems, he did not pay any attention to the “sore in the mouth.” The mass did not increase appreciably in size, according to the patient, until 1 week prior to my seeing him. At that time, it began to enlarge to its present size, which was about that of a large pecan. The patient was not receiving any form of antibiotic therapy, so he was placed on a regimen of Combiotic, 2 C.C. intramuscularly twice a day, and 50 mg. Demerol intramuscularly every 4 hours as needed for pain. By the following afternoon he was much more comfortable, and there was less tenderness on each side of the mandible. On December 8 he underwent a transurethral resection, and a definitive diagnosis of “well-differentiated invasive adenocarcinoma of the prostate gland” was made. On December 12 an exploratory procedure was carried out on the mass on the right side of the mandible with the expectation that incision and drainage would be necessary. Preoperatively, there was a remote possibility of a metastatic lesion from the prostate as a secondary diagnosis. Procedure
At 1 P. M. on December 12 the patient was taken to the operating room, where he was anesthetized with Pentothal sodium, intubated nasally, and carried along on nitrous oxide, oxygen, and Fluothane. At this time, an intraoral examination revealed a fluctuant mass on the right side approximately opposite the right first molar area. It was thought that this might possibly represent a residual abscess formation. Therefore, an incision was made directly over the mass intraorally. It was noted that no pus was present but that there was a purplish mass just beneath the mucous membrane. By careful blunt and sharp dissection, the plane around the mass was established, and it was enucleated as completely as possible. It was also noted that there was some invasion of the bone, forming a possible osteolytic lesion. The inferior alveolar canal waa demonstrated at this point, and some of the bone was removed by means of rongeurs. The area was packed with Gelfoam and closed with 3-O black silk. An incision was then made over the mass on the left side. This time, by careful dissection, the mass was brought into view, and the planes of encapsulation were found. The lesion appeared to be more encapsulated and not attached to the bone; nor had it invaded the bone. There was some erosion of the bone, but it was smooth and no osteolytic process could be demonstrated. The mass was sent for frozen section, and the pathologist reported that this was a benign lesion. The area was then packed with Gelfoam and closed with 3-O black silk. The tissue from the right side was sent for routine examination. Following extubation, the patient was sent to the recovery room in excellent condition. A complete bone survey was performed on December 13, and no osteolytic lesions were found in any other bone of the body. Roentgenograms of the cervical spine, however, did show changes consistent with old rheumatoid arthritis, with some hypertrophic bridging between the last two cervical segments. On December 14 the pathologist informed us that this was undoubtedly an angiosarcoma of the mandible. It was thought that this could be a primary lesion even though it was bilateral. The pathologist was of the opinion that the left side was probably corn-
158
Calhoun
O.S., 0.x February,
& 0.1’. 1969
pletely enucleatecl but that the right side had not been completely rcnloved because of 1111: bone invasion noted at the time of surgical intervention. With this probability in mind, the case was presented to the Tumor Board at Memorial Hospital in Phoenix, Arizona, on December 16. It was recommended that the patient receive 0.5 mg. of actinompcin D intravenously every day for 5 days. Cobalt irradiation was to begin on the third day of actinomycin D treatment and was to be carried to tumor dose and/or toxicity. The lesion on the right side had grown until it was almost double its former size. On December 28 this treatment was begun on an inpatient basis at Memorial Hospital. The patient received actinomycin D and the cobalt therapy was begun on the third day. 11~ was discharged from the hospital on December 31, to follow the course of cobalt therapy as an outpatient. The lesion on the right side of the mandible responded very well to the cobalt therapy, as it melted almost completely away. There was some resulting breakdown of the incision, as well as some exposure of the bone. The lesion on the left had not recurred and, therefore, received no cobalt irradiation. During t.his time, the patient was experiencing some prostatic or urinary problems in His urologist had placed him on “hormone that he was having a constant hematuria. therapy” for the prostatic carcinoma at the time of the original discharge from the hospital. The patient seemed to be responding nicely am1 was improving on the cobalt and hormone therapy until Jan. 22, 1967. At that time he was readmitted to the Mesa Lutheran Hospital’s Orthopedic Service with severe pain beneath the right sternocleidomastoid muscle. He was placed in cervical traction, which had to be discontinued almost immediately because of a severe erythematous reaction to the face and neck due to the cobalt. There was slight improvement during the folIonTing week. He did, however, continue to receive the cobalt therapy at Memorial Hospital. On January 27 the case was re-presented to the Tumor Board. The Board thought there was a po’ssibility that an abscess was forming beneath the sternocleidomastoid muscle and that the patient should be given large doses of chloramphenicol and vigorous heat therapy. If there was no relief, a fasciotomy of that area should be considered. This treatment was instituted, and during the following week the pain subsided and the patient felt better. He was subsequently discharged from the hospital on February 3. On February 6 the patient was seen in our office as an outpatient. At this time, the neck pain was returning and he was placed on heat therapy but no antibiotics. Again the pain subsided. It was thought at this time that a mass was definitely palpable behind the sternocleidomastoid muscle. For this reason, the case was again presented to the Tumor Board, where the consensus was that a definite mass was present and that it was undoubtedly metastatic from the mandible. The patient was given another course of actinomycin D in the same dosage as before, and cobalt irradiation was again instituted on the third day. The rationale of the aetinomycin D is to sensitize the tumor to cobalt. The portal of cobalt irradiation was the right sternocleidomastoid muscle. The treatment was begun on February 3.3. There did not seem to be the marked improvement that had been hoped for or that had been seen the first time The patient followed a progressively downhill course, physically, and on February 17 it was thought that he was developing “Homer’s syndrome.” On February 20 the patient was readmitted to the Mesa Lutheran Hospital Medical Service. The admitting diagnosis was (1) angiosarcoma of the mandible with metastatic lesions and (2) moderate to severe debilitation. A Foley catheter was inserted, and it was noted that there was free blood in the urine. On admission, the bilirubin was slightly elevated. Platelets were somewhat depressed to 110,000; the white count was elevated-16,256, with 80 segmented leukocytes, 4 bands, 12 lymphocytes, and 4 eosinophils. There were no other significant laboratory findings. Physical examination at that time showed an elderly, obviously ill man who responded sluggishly to questioning. The blood pressure was 132/78;
Volume Number
27 2
Malignant
hemangioendothelioma
159
temperature, 102” F.; and pulse, 128. The weight was 169 pounds. The patient was pale. Marked moist riles were present in the upper right and midlung fields. Atria1 fibrillation was present, with murmurs of mitral insufficiency. Abdominal examination did not reveal any masses or tenderness. The hospital course was downhill, and the patient died on February 21. A postmortem examination was performed on February 22. Autopsy
findings
Grossly, there was a purplish, gelatinous type of tumor in the region of the adrenal glands, consistent with the angiosarcoma found originally in the mandible. The bladder was full of the same type of tumor formation. When the heart was opened, a similar mass was found in the atria1 septum. There was also tumor formation beneath 6he right sternocleidomastoid muscle, but this showed some signs of having been treated and looked as though it were regressing. It did not have the same malignant appearance. The diagnosis of angiosarcoma of the aforementioned organs was subsequently confirmed by means of microscopic sections.
DISCUSSION It has been shown that the occurrence of angiosarcoma or malignant hemangioendothelioma is very rare. There is little dissent in the literature regarding the eventual outcome of an advanced case of angiosarcoma. Also, there is little argument that it is an extremely malignant and fast-growing tumor. Most histopathologists agree that t,his type of tumor arises from the endothelial lining of the vascular tree. It is recognized that there is little organization of the tumor cells and that they may even completely obliterate the vascular channels. Recently, through electron microscopy, the characteristic silver reticulin staining has been found to be due to the condensation into strata of the fine fibrillar and flocculent extracellular material. In the case presented here, we have shown a bilateral angiosarcoma in the area of the mandible and involving the bone on the right side. It has also been shown that this was probably a metastatic lesion from the heart; however, this is only conjecture. It is not likely that the tumor of the mandible was of primary origin, since the lesion was bilateral, with the primary origin probably in the heart. This case tends to point out more strongly the malignancy of this tumor and the extreme rapidity of its growth. It is interesting to note the tumor’s strange proclivity for certain organs. As was mentioned in the opening portion of this article, the tumor has been found in kidney, skin, bone, heart, and lungs. In this case, all but the skin and lungs were involved. SUMMARY In retrospect, in view of the negative bone survey and also the pain beneath the right sternocleidomastoid muscle, it seems that one should have considered the possibility of a metastatic lesion from some internal soft-tissue organ, the heart being the most likely. It is also possible that, through some form of angiography, a diagnosis could have been made, thereby permitting treatment with actinomycin D and local cobalt irradiation to the heart. This case also helps to point up the fact that this tumor is difficult to diagnose and that it has the ability to mimic other much less malignant diseases.
160
Calhom
03, ox. .Februarp,
& 0.1’. 1969
REFERENCES
1. Ackerman, Lauren V.: Surgical Pathology, ed. 2, St. Louis, 1959, The C:. 1’. JIosby Cumpany, p. 855. 2. Ramsey, Helen J.: Fine Structures of Hemangiopericytoma and Hemangio-endothelioma, Cancer 19: 2005-2017, 1966. 3. Thoma, K. H., and Goldman, H. M.: Oral Pathology, ed. 5, St. Louis, 1960, The C. V. Mosby Company, p. 1399. 431 West 5th PI.