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Malignant chondroid syringoma with widespread metastasis
Volume 22 Number 5, Part I May 1990
Brief communications 845 lar lymphocytic infiltrate in the papillary dermis." Evidence of vascular damage has been found in three cases.2,4, 5 In our patient the specimen from the chest was not diagnostic of erythema multi forme whereas that from the hand revealed features of an immune complex vasculitis. We believethat the term erythema multiforme cannot be correctly applied to this eruption and that a more suitable designation, postradiation polymorphic dermatitis, should be adopted. REFERENCES
.
"
':: .": :
•.•
f._
•
0.
I. Epstein P. Severe general vascular injuries simulating Werlhof's disease following intensive local roentgen ray treatment. Strahlentherapie 1924;21 :416-9. 2. Chalmers D. A fatal case of erythema multiforme following deep x-ray therapy. Br J DermatoI1959;71:256-60. 3. Maxfield WS. Coleman WP. Cutaneous reactions after radiation therapy. Am J Roentgenol 1969;105:636-43. 4. Porter EC, Wadsworth RC. Generalized skin eruptions during radiotherapy. J Maine Med Assoc 1976;67:267-74. 5. Loewe L, Carniel MR. Exanthem complicating neoplastic disease. Am J RoentgenoI1940;43:587-96. 6. Salomon D, Saurat GH. Erythema multiforme and radiotherapy [Abstract]. Dermatologica 1988;177:258.
--~
Fig. 2. Photomicrograph of biopsy specimen of hand lesion shows normal epidermis overlying dense, perivascular, polymorphic infiltrate with endothelial swelling, extravasated erythrocytes, and modest leukocytoclasia. (XIOO.) for abatement. Eosinophilia, leukopenia, and mild kidney damage may be present. The condition is self-limited, although in two cases the outcome was fatal. l, 2Treatment includes antihistamines and systemic corticosteroids-; antibiotics may be useful as well." Deep x-ray treatment is undoubtedly the cause. Attempts to reproduce the disorder in the same patient have been successful, and even diagnostic x-rays 8 years later may evoke a response. Reactions to histamine, to a toxic substance, or to antigens liberated from the irradiated tumor' have been suggested as pathogenetic mechanisms. Our case is representative of this entity. No clinical or laboratory evidence of an infectious disease was found, and drug allergy was ruled out. The patient had been taking his medications for years, and their reintroduction did not cause the rash to recur. The classification of this eruption as erythema multiforme seems to rest in its polymorphic appearance rather than in the true dermatologic definition of the disease. Histopathologic studies have been performed in only 10 of 82 reported cases,2.4-6 and only in 4 was it compatible with erythema rnultiforme.v'' In the remaining cases it was nonspecific and consisted of edema and a perivascu-
Malignant chondroid syringoma with widespread metastasis James C. Steinmetz, MD,a Barbara A. Russo, MD,b and Ronald E. Ginsburg, MD C Houston, Texas, and Manhasset and Albany, New York Chondroid syringoma is an uncommon type of sweat gland tumor. Most reported cases are benign, but there are several examples with malignant behavior."! Synonyms for malignant chondroid syringoma (MCS) include "malignant mixed tumor of skin," "aggressive chondroid syringoma," and "metastasizing chondroid syringoma." We report a fatal case of a widely metastatic MCS and review the features of this tumor. Case report. A 59-year-old white man noticed a mass over the right scapula that became larger and increasingly painful during a 6-week period. He also had anorexia, fatigue, and a weight loss of 25 pounds during the previous 3 months. Excisional biopsyofa4.0 X 2.5 X 1.6em subcutaneous mass was performed, and the tumor was diagnosed as an MCS after consultation with From the University of Texas M. D. Anderson Cancer Center, Houston,' the North Shore University Hospital, Manhasset.s and the AI· bany Veterans Administration Medical Center," Reprint requests: James C.Steinmetz, MD, Department of Pathology, Box085,University ofTexas M. D. Anderson Cancer Center, ISIS Holcombe Blvd., Houston, TX 77030.
16/4/15998
846
Journal of the American Academy of Dermatology
Brief communications
Fig. 1. Cerebellar metastasis shows mixed differentiation of tumor with polygonal epithelial cells (left) and chondroid differentiation (right). (Hematoxylin-eosin stain; X60.) the Armed Forces Institute of Pathology. Wider excision was then performed, but no residual neoplasm was identified. Two weeks later the patient was admitted to the Albany Veterans Administration Medical Center for further examination. On admission the patient had cervical lymphadenopathy and paraspinal tenderness. Computed tomographic scan of the abdomen showed probable liver metastases, ascites, and bilateral pleural effusions. One week after admission the patient had a grand mal seizure and computed tomographic scan of the head showed brain metastases. Thereafter the patient remained comatose. He became progressively hypotensive and died 2 days after the seizure, 9 weeks after the scapular mass had been excised. At autopsy metastatic necrotic tumor nodules were found in most organs. Microscopically, the well-preserved areas showed a mixture of cell types. The epithelial component consisted of anaplastic polyhedral cells with focal differentiation into acinar formations and moderate numbers of normal and atypical mitotic figures. Most of the metastatic focialso contained areas of cartilaginous differentiation (Fig. 1).
Discussion. MCS was first reported by Hirsch and Helwig! in 1961. We are aware of 18 other cases of chondroid syringoma with histologically aggressive features or with a history of local recurrence and/or metastasis.s" These 19 cases, together with ours, are summarized in Table I. Most early cases of MCS occurred in women, and in the 20 cases the female/male ratio is 2.3:1. MCS has occurred in patients aged 13 to 83 years, with a median age of 57 years. In contrast to its benign counterpart, MCS occurs predominantly on the extremities (eight lower, five upper) and trunk (three cases). At presentation the tumor masses had a median size of 4 em (range 1.4 to 10 ern) in greatest diameter. The histopathologic findings of MCS consist of a combination of epithelial and mesenchymal elements. The
epithelial cells have been most frequently described as polygonal, with varying degrees of pleomorphism and up to five mitotic figures per high power field. The epithelial cellshave been reported to form trabeculae, islands, cords, tubules, ducts, acini, papillae, tuboalveoli, or glands. One case each contained squamous cell carcinoma in the primary tumor, squamous cell carcinoma in metastases, and well-differentiated squamous epithelium in the primary tumor. In virtually all cases a stroma was described as myxoid or mucinous. The mesenchymal element is usually cartilaginous; various authors report hyaline cartilage, fibrocartilage, pseudocartilage, chondroid metaplasia of stroma, or chondroid-appearing physaliphorous cells.One case had areas of bone formation in the primary tumor. The histologic features that distinguish MCS from benign chondroid syringoma include cytologic atypia, pleomorphism, increased mitotic activity, and focal necrosis. The epithelial component shows a lesser degree of tubular differentiation than in benign chondroid syringoma. Many MCS have an irregular, infiltrative border or evident vascular invasion. It is emphasized that at least two reported cases (that of Ishimura et al. and second case of Dissanayake and Salm) lacked all of these histologic features of malignancy but still metastasized. Ishimura et a1. 4 noted that both these cases had a large amount of mucoid matrix with poor chondroid differentiation and that this pattern may indicate the potential for malignant
behavior." Of the 20 cases of MCS, 7 recurred locally, 12 metastasized to the lymph nodes, and 11 metastasized to the viscera. It is noteworthy that three cases did not recur or metastasize, and despite aggressive histologic features, the adjective malignant might be questioned under these circumstances.
Volume 22 Number 5, Part I May 1990
Brief communications 847
Table I. Summary of 20 reported cases of malignant chondroid syringoma Lymph node Author(s)
Hirsch and Helwig Sharvill
1
50jF Face
2,4*
39jF R wrist 2
Rosborough
2,4*
83jF Larrn
Matz et al.
2,4*
Schremmer Hilton et al. Lucas and Nordby Webb and Stott Botha and Kahn Dissanayake and Salm
2* 2,4* 2*
74jF
2,4*
52jF R thigh 10
2*
15jF Lear
2,4*
79jF Sacrum 8
Harrist et al. (2 cases)
2
Redono et al. Ishimura et al.
4* 4
DeMoraes et al. Shvili and Rothern Hermann et al.
5 6
Clark Our case
Course
metastasis
7 8
NA No
No
No
Yes
No
No
3
No
Axillary
No
80jF Scalp
5
Yes
Cervical
55jM Finger
3 NA 3.7 Yes NA Yes
Axillary Axillary No
Widespread NA Lungs Alive and well at 17 yr No Alive and well at No 24 mo Alive and well at No 18 mo No Alive and well at 6 yr
I4jF
Larm L hand
Yes
NA Yes
Inguinal No
Alive and well at 18 rno Excision of recurrence at 36 rno Alive and well at 17 rno Dead of diseaseat 84 mo
Dead of disease at 1 yr 33jM L foot NA No Lungs Lost to follow-up No Dead of disease at 70jM L foot 8 Yes Inguinal Bone, 7 yr (Ref 3) lungs Alive and well at 1 yr 69jM L thigh 4 No No No 6IjF Rfoot 2.5 Yes (4X) Inguinal Lungs NA Dead of disease 73jM Back 7 WideYes Cervical spread at 13 yr 23jF R leg 4 Supraclavicular Lungs NA No 44jF Buttocks 5 No Inguinal Dead of disease Widespread at 6 rno 13jF Scalp Dead of disease 1.4 Yes (3X) Cervical Bone at 34 rno 74jF R thigh 8 NA NA NA NA 59jM Back 4 No Dead of disease Mediastinal Widespread at 9 wk No
No
Lungs
Left; NA. not available; R. right. *Cases reviewed in reference(s).
L.
For the 15 cases for which follow-up information is available, eight patients were still alive for periods ranging from 17 months to 17 years after initial diagnosis. The seven patients who died did so within 9 weeksto 13 years after presentation. REFERENCES 1. HirschP, Helwig EB.Chondroid syringoma: mixed tumor of skin, salivary gland type. Arch Dermatol 1961;84:83547.
2. Harrist TJ, Aretz TH, Mihm MC, et al. Cutaneous malignant mixed tumor. Arch Dermatol 1981 ;117:7 I9-24. 3. Devine P,SarnoRC, Ucci AA. Malignant cutaneous mixed tumor [Letter]. Arch Dermatol 1984;120:576-7.
4. Ishimura E, Iwamoto H, Kobashi Y, et al. Malignant
chondroid syringoma: reportof a casewithwidespread metastasis and review of pertinent literature. Cancer 1983; 52:1966-73. 5. DeMoraes HP, HerreraGA, Mendonca AMN, et al. Met-
astaticmalignant mixed tumor of skin: ultrastructural and immunocytochemical characterization, histogenetic considerations, and comparison with benign mixed tumors of skinand salivary glands. Appl Pathol 1986;4:199-208. 6. Shvili D, Rothem A. Fulminant metastasizing chondroid syringoma of the skin. Am J Dermatopathol 1986;8:321-5. 7. Hermann G, Moss D, Norton KI, et al. Case report 450. Skeletal Radiol 1987;16:657-9. 8. Clark P. Malignant chondroid syringoma. Conn Med 1987;5 1:569-72.
Brief communications 845 lar lymphocytic infiltrate in the papillary dermis." Evidence of vascular damage has been found in three cases.2,4, 5 In our patient the specimen from the chest was not diagnostic of erythema multi forme whereas that from the hand revealed features of an immune complex vasculitis. We believethat the term erythema multiforme cannot be correctly applied to this eruption and that a more suitable designation, postradiation polymorphic dermatitis, should be adopted. REFERENCES
.
"
':: .": :
•.•
f._
•
0.
I. Epstein P. Severe general vascular injuries simulating Werlhof's disease following intensive local roentgen ray treatment. Strahlentherapie 1924;21 :416-9. 2. Chalmers D. A fatal case of erythema multiforme following deep x-ray therapy. Br J DermatoI1959;71:256-60. 3. Maxfield WS. Coleman WP. Cutaneous reactions after radiation therapy. Am J Roentgenol 1969;105:636-43. 4. Porter EC, Wadsworth RC. Generalized skin eruptions during radiotherapy. J Maine Med Assoc 1976;67:267-74. 5. Loewe L, Carniel MR. Exanthem complicating neoplastic disease. Am J RoentgenoI1940;43:587-96. 6. Salomon D, Saurat GH. Erythema multiforme and radiotherapy [Abstract]. Dermatologica 1988;177:258.
--~
Fig. 2. Photomicrograph of biopsy specimen of hand lesion shows normal epidermis overlying dense, perivascular, polymorphic infiltrate with endothelial swelling, extravasated erythrocytes, and modest leukocytoclasia. (XIOO.) for abatement. Eosinophilia, leukopenia, and mild kidney damage may be present. The condition is self-limited, although in two cases the outcome was fatal. l, 2Treatment includes antihistamines and systemic corticosteroids-; antibiotics may be useful as well." Deep x-ray treatment is undoubtedly the cause. Attempts to reproduce the disorder in the same patient have been successful, and even diagnostic x-rays 8 years later may evoke a response. Reactions to histamine, to a toxic substance, or to antigens liberated from the irradiated tumor' have been suggested as pathogenetic mechanisms. Our case is representative of this entity. No clinical or laboratory evidence of an infectious disease was found, and drug allergy was ruled out. The patient had been taking his medications for years, and their reintroduction did not cause the rash to recur. The classification of this eruption as erythema multiforme seems to rest in its polymorphic appearance rather than in the true dermatologic definition of the disease. Histopathologic studies have been performed in only 10 of 82 reported cases,2.4-6 and only in 4 was it compatible with erythema rnultiforme.v'' In the remaining cases it was nonspecific and consisted of edema and a perivascu-
Malignant chondroid syringoma with widespread metastasis James C. Steinmetz, MD,a Barbara A. Russo, MD,b and Ronald E. Ginsburg, MD C Houston, Texas, and Manhasset and Albany, New York Chondroid syringoma is an uncommon type of sweat gland tumor. Most reported cases are benign, but there are several examples with malignant behavior."! Synonyms for malignant chondroid syringoma (MCS) include "malignant mixed tumor of skin," "aggressive chondroid syringoma," and "metastasizing chondroid syringoma." We report a fatal case of a widely metastatic MCS and review the features of this tumor. Case report. A 59-year-old white man noticed a mass over the right scapula that became larger and increasingly painful during a 6-week period. He also had anorexia, fatigue, and a weight loss of 25 pounds during the previous 3 months. Excisional biopsyofa4.0 X 2.5 X 1.6em subcutaneous mass was performed, and the tumor was diagnosed as an MCS after consultation with From the University of Texas M. D. Anderson Cancer Center, Houston,' the North Shore University Hospital, Manhasset.s and the AI· bany Veterans Administration Medical Center," Reprint requests: James C.Steinmetz, MD, Department of Pathology, Box085,University ofTexas M. D. Anderson Cancer Center, ISIS Holcombe Blvd., Houston, TX 77030.
16/4/15998
846
Journal of the American Academy of Dermatology
Brief communications
Fig. 1. Cerebellar metastasis shows mixed differentiation of tumor with polygonal epithelial cells (left) and chondroid differentiation (right). (Hematoxylin-eosin stain; X60.) the Armed Forces Institute of Pathology. Wider excision was then performed, but no residual neoplasm was identified. Two weeks later the patient was admitted to the Albany Veterans Administration Medical Center for further examination. On admission the patient had cervical lymphadenopathy and paraspinal tenderness. Computed tomographic scan of the abdomen showed probable liver metastases, ascites, and bilateral pleural effusions. One week after admission the patient had a grand mal seizure and computed tomographic scan of the head showed brain metastases. Thereafter the patient remained comatose. He became progressively hypotensive and died 2 days after the seizure, 9 weeks after the scapular mass had been excised. At autopsy metastatic necrotic tumor nodules were found in most organs. Microscopically, the well-preserved areas showed a mixture of cell types. The epithelial component consisted of anaplastic polyhedral cells with focal differentiation into acinar formations and moderate numbers of normal and atypical mitotic figures. Most of the metastatic focialso contained areas of cartilaginous differentiation (Fig. 1).
Discussion. MCS was first reported by Hirsch and Helwig! in 1961. We are aware of 18 other cases of chondroid syringoma with histologically aggressive features or with a history of local recurrence and/or metastasis.s" These 19 cases, together with ours, are summarized in Table I. Most early cases of MCS occurred in women, and in the 20 cases the female/male ratio is 2.3:1. MCS has occurred in patients aged 13 to 83 years, with a median age of 57 years. In contrast to its benign counterpart, MCS occurs predominantly on the extremities (eight lower, five upper) and trunk (three cases). At presentation the tumor masses had a median size of 4 em (range 1.4 to 10 ern) in greatest diameter. The histopathologic findings of MCS consist of a combination of epithelial and mesenchymal elements. The
epithelial cells have been most frequently described as polygonal, with varying degrees of pleomorphism and up to five mitotic figures per high power field. The epithelial cellshave been reported to form trabeculae, islands, cords, tubules, ducts, acini, papillae, tuboalveoli, or glands. One case each contained squamous cell carcinoma in the primary tumor, squamous cell carcinoma in metastases, and well-differentiated squamous epithelium in the primary tumor. In virtually all cases a stroma was described as myxoid or mucinous. The mesenchymal element is usually cartilaginous; various authors report hyaline cartilage, fibrocartilage, pseudocartilage, chondroid metaplasia of stroma, or chondroid-appearing physaliphorous cells.One case had areas of bone formation in the primary tumor. The histologic features that distinguish MCS from benign chondroid syringoma include cytologic atypia, pleomorphism, increased mitotic activity, and focal necrosis. The epithelial component shows a lesser degree of tubular differentiation than in benign chondroid syringoma. Many MCS have an irregular, infiltrative border or evident vascular invasion. It is emphasized that at least two reported cases (that of Ishimura et al. and second case of Dissanayake and Salm) lacked all of these histologic features of malignancy but still metastasized. Ishimura et a1. 4 noted that both these cases had a large amount of mucoid matrix with poor chondroid differentiation and that this pattern may indicate the potential for malignant
behavior." Of the 20 cases of MCS, 7 recurred locally, 12 metastasized to the lymph nodes, and 11 metastasized to the viscera. It is noteworthy that three cases did not recur or metastasize, and despite aggressive histologic features, the adjective malignant might be questioned under these circumstances.
Volume 22 Number 5, Part I May 1990
Brief communications 847
Table I. Summary of 20 reported cases of malignant chondroid syringoma Lymph node Author(s)
Hirsch and Helwig Sharvill
1
50jF Face
2,4*
39jF R wrist 2
Rosborough
2,4*
83jF Larrn
Matz et al.
2,4*
Schremmer Hilton et al. Lucas and Nordby Webb and Stott Botha and Kahn Dissanayake and Salm
2* 2,4* 2*
74jF
2,4*
52jF R thigh 10
2*
15jF Lear
2,4*
79jF Sacrum 8
Harrist et al. (2 cases)
2
Redono et al. Ishimura et al.
4* 4
DeMoraes et al. Shvili and Rothern Hermann et al.
5 6
Clark Our case
Course
metastasis
7 8
NA No
No
No
Yes
No
No
3
No
Axillary
No
80jF Scalp
5
Yes
Cervical
55jM Finger
3 NA 3.7 Yes NA Yes
Axillary Axillary No
Widespread NA Lungs Alive and well at 17 yr No Alive and well at No 24 mo Alive and well at No 18 mo No Alive and well at 6 yr
I4jF
Larm L hand
Yes
NA Yes
Inguinal No
Alive and well at 18 rno Excision of recurrence at 36 rno Alive and well at 17 rno Dead of diseaseat 84 mo
Dead of disease at 1 yr 33jM L foot NA No Lungs Lost to follow-up No Dead of disease at 70jM L foot 8 Yes Inguinal Bone, 7 yr (Ref 3) lungs Alive and well at 1 yr 69jM L thigh 4 No No No 6IjF Rfoot 2.5 Yes (4X) Inguinal Lungs NA Dead of disease 73jM Back 7 WideYes Cervical spread at 13 yr 23jF R leg 4 Supraclavicular Lungs NA No 44jF Buttocks 5 No Inguinal Dead of disease Widespread at 6 rno 13jF Scalp Dead of disease 1.4 Yes (3X) Cervical Bone at 34 rno 74jF R thigh 8 NA NA NA NA 59jM Back 4 No Dead of disease Mediastinal Widespread at 9 wk No
No
Lungs
Left; NA. not available; R. right. *Cases reviewed in reference(s).
L.
For the 15 cases for which follow-up information is available, eight patients were still alive for periods ranging from 17 months to 17 years after initial diagnosis. The seven patients who died did so within 9 weeksto 13 years after presentation. REFERENCES 1. HirschP, Helwig EB.Chondroid syringoma: mixed tumor of skin, salivary gland type. Arch Dermatol 1961;84:83547.
2. Harrist TJ, Aretz TH, Mihm MC, et al. Cutaneous malignant mixed tumor. Arch Dermatol 1981 ;117:7 I9-24. 3. Devine P,SarnoRC, Ucci AA. Malignant cutaneous mixed tumor [Letter]. Arch Dermatol 1984;120:576-7.
4. Ishimura E, Iwamoto H, Kobashi Y, et al. Malignant
chondroid syringoma: reportof a casewithwidespread metastasis and review of pertinent literature. Cancer 1983; 52:1966-73. 5. DeMoraes HP, HerreraGA, Mendonca AMN, et al. Met-
astaticmalignant mixed tumor of skin: ultrastructural and immunocytochemical characterization, histogenetic considerations, and comparison with benign mixed tumors of skinand salivary glands. Appl Pathol 1986;4:199-208. 6. Shvili D, Rothem A. Fulminant metastasizing chondroid syringoma of the skin. Am J Dermatopathol 1986;8:321-5. 7. Hermann G, Moss D, Norton KI, et al. Case report 450. Skeletal Radiol 1987;16:657-9. 8. Clark P. Malignant chondroid syringoma. Conn Med 1987;5 1:569-72.