HUMAN PATHOLOGY
Volume 22, No. 10 (October
ADDENDUM
squamous carcinoma may be a collision tumor and that the squamous component may have developed from squamous metaplasia following radiation or hormonal therapy. Moyana’ and Lager et al’ propose that the adenosquamous carcinoma of the prostate is derived from resident pluripotent stem cells capable of multidirectional differentiation. This report supports the existence of a pluripotent stem cell that, following appropriate stimuli (such as irradiation or estrogen therapy), alters its line of differentiation. The altered differentiation may account for the lack of expression of “normal” prostatic antigens (PAP and PSA) in the metaplastic and malignant squamous cells. The squamous component in this case, although appearing well differentiated by light microscopy, shows no specific ultrastructural features of either an adenocarcinoma or a squamous cell carcinoma. As an aneuploid peak was not identified in either malignant component by flow cytometry or image analysis, the presence of two separate tumors differentiating from a pluripotent stem cell is neither supported nor overruled.
Since this paper was accepted for publication, Wernert et al7 have described two cases of prostatic adenocarcinoma with a malignant squamous component occurring after estrogen treatment. They suggest that the basal cells of the prostatic gland, in which they have identified nuclear estrogen receptors, undergo squamous metaplasia in response to estrogen treatment, and suggest that this may be a precursor of the malignant squamous component. The authors thank Saundra Dalton for typing Acknowkdgmen~ the manuscript, and the Audio-Visual Department, Royal College of Surgeons in Ireland, for photographic assistance.
REFERENCES 1. Green LF, Mulcahy JJ, Warren MM, et al: Primary transitional cell carcinoma of the prostate. J Ural 110:235-237. 1973 2. Saito R. Davis BK, Ollapally EP: Adenosquamous carcinoma of the prostate. HUM PATHOI. 15:87-89, 1984 3. Lager DJ, Goeken JA. Kemp JD, et al: Squamous metaplasia (>f the prostate-An immunohistochemical study. Am J Clin Pathol 90:597-601. 1988 4. Bainborough AR: Squamous metaplasia uf prostate following oestrogell therapy. J Ural 68:329-336. 1952 5. Bennett RS. Edgerton EO: Mixed prostatic carcinoma. J L’rol I l&561563, 1973 6. Moyana TN: Adenosquamous carcinoma of the prostate. Am J Surg Pathol 11:403-407. 1987 7. Wernert N, Goebbels R, Bonkhoff H, et al: Squamous cell carcirloma of the prostate. Histopathology 17:339-344, 1990
CONCLUSION In conclusion, despite the common occurrence of mixed types of carcinomas in other sites such as the lung, adenosquamous carcinoma of the prostate is exceedingly rare with, including this report, only four documented cases in the world literature. Estrogen therapy, being administered in three cases, may be implicated in the development of these unusual mixed tumors.
GRANULOMATOUS AORTIC IN TAKAYASU AORTITIS LYNDA
RUSHING,
MD,
FREDERICK
From the Departments
VALVULITIS
of Pathology
ASSOCIATED
MD, PHD,
J. SCHOEN,
and Vascular
ALAN
Medicine,
Brigham and Women’s Hospital, Boston, MA; and the Department
of Pathology, Mayo Clinic Foundation, oublication December 10. 1990. *Present address: Cardiovascular
nesota, Minneapolis, MN.
Rochester,
MN. Accepted
for
Division, University of Min-
1991)
WITH
HIRSCH,*
AORTIC
MD,
INSUFFICIENCY
AND J. T. LIE,
MD
We report an unusual CUSPof Takayasu aortitis associated with a giant cell granulomatous ualvulitis presenting with aortic ins@ciency. Although nonspecific valuular abnormalities have been reported with Takayasu aortitis, this case is the first to describe inuolvemxnt of the aortir valve by the disease. HLL~PATHOI. 22: 10501053. Copyright 0 1991 by W. B. Saunders Company
Key words: aortitis,
valvulitis, Takayasu aortitis. Address correspondence and reprint requests to Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women’s
Hospital, 75 Francis St, Boston, MA 02115. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91/2210-0015$5,00/O
Takayasu aortitis is an inflammatory vascular disease of uncertain etiology. Classically. this disorder affects young women, usually of Asian descent, diminished pulses, hypertension.
1050
who present with absent or or claudication.’ Other, less
CASE STUDIES
FIGURE 1. Aorta. (Top) Low-power photomicrogroph of an aorta demonstrating disruption of medial elastic fibers and thickenNed intima and adventitia. The luminal surface is at the top. (Elastin stain; magrlification X40.) (Bottom) High-power view of aortic media with a lymphohistiocytic infiltrate and a multinucleated giant cell. (Hematoxylineosin stain; magnification X 140.)
common clinical presentations of the disease have been described, such as rupture and dissection of the thoracic aorta’ and coronary ischemia.“,’ Aortic insufficiency as a presenting clinical feature in Takayasu aortitis is unusual.“,” The patient reported here had aortic insufficiency as the initial manifestation of Takayasu aortitis. associated with the unique finding of granulomatous aortic valvulitis. REPORT
OF
24 CASE
A 3+year-old for elective aortic
white woman was admitted to the hospital valve rrplacement. Aortic insufficiency was
noted 6 years earlier at the time of her second pl-egnancv. Present symptoms included onl\ a sense of “prominent pt;lsations” in her neck. She specificallv denied fever. malaise. weight loss. arm or leg claudication. prior rheumatic fever, OI a family history of congenital heart disease. There was no history of hypertension. Phystcal examination, echoc;lrdiogr;lph); with doppler cxamination, and cardiac catheterization demonstrated severe aortic insufficiency, annuloaortic ectasia (aortic. I-oot cliametrr. 5.6 cm; normal, 2 to 3 cm). left ventricular enlargement with mildly decreased function, and normal coronan artc.rics. Ka-
1051
HUMAN PATHOLOGY
Volume 22, No. 10 (October
1991)
FIGURE 2. Aortic valve. (Top) Lowpower photomicrograph demon ,strating superficial and deep granul omatous inflammation of the aortic Ltalve. (Hematoxylin-eosin stain; magr lification x150.) (Bottom) Higher-p Newer view demonstrating giant cells. (Hematoxylin-eosin stain; magnitic ation X375.)
diai, femoral, and pedal pulses were normal. There were no flank or abdominal bruits. She underwent elective replacement of the aortic valve and ascending aorta by a valved conduit without complications. PATHOLOGIC
FINDINGS
Microscopic examination of the ascending aorta revealed a thickened intima, focal attenuation, and degeneration of the media, with loss of smooth muscle and elastic elements and
focal medial infarcts (Fig 1). The adventitia was thickened and there was transmural loss of elastic elements in some areas. Active inflammation was present in all three layers and appeared to consist of predominantly mononuclear cells with lymphocytes, histiocytes, and giant cells. In occasional areas where the aortic wall was largely intact, there was no cystic medial degeneration or other abnormality noted. Special stains for spirochetal, fungal, and bacterial organisms were negative. Histologic sections through the aortic valve revealed an active valvulitis extending from and morphologically similar
1052
CASE STUDIES to the aortic disease. There was a dense mononuclear infiltrate, composed predominantly of lymphocytes with focal neutrophils and hi.stiocytes and occasional giant cells (Fig 2). The uninvolved portions of the \-alve contained areas of intimal proliferation1 and myxomatous change. DISCUSSION The unique feature of this case is the presence of a giant cell granulomatous valvulitis in association with the aortitis. which, to our knowledge, has not been previously described in Takayasu aortitis. A report by Saito et al’ of five autopsied cases oi “aortitis syndrome” described a diffuse round cell infiltrate in the aortic. valve of one of the patients. The infiltrate was described as being present from the subendothelium to the media; hl)wever, there was no mention of a granulomatous component. Other reports’,’ of valvular abnormalities in Takayasi’s disease described a nonspecific fibrosis with or without mononuclear cells. A recent report’” described a patient with Reiter’s syndrome who had a severe giant cell valvulitis of both mitral and aortic valves with an otherwise nongranulomatous aor-titis. To our knowledge, this is the only other previous report of giant cell granulomatous valvulitis. The difrerential diagnosis of giant cell granulomatous aortitis includes syphilitic aortitis and giant cell arteritis, which can be morpholo@cally indistinguishable from Takayasu aortitis.” Takdyasu aortitis has also been described in association with systemic rheumatologic diseases such as rheumatoid arthritis, ankylosing spondylitis, and progressive systemic sclerosis.“,” Although thr patient reported here may have an underlying rheumatologic disorder that has yet to become overt, the oresence of all underlvincr disease does not exclude the diagLosis of Takayasu aortitis.Y Moreover, both syphilitic and tenlporal giant cell arteritis are unlikely possibilities, in view of the patient’s age and the clinical setting. The patient was
young and had no other stigmata commonly associated with syphilitic or temporal giant cell arteritis. Finally, aortir insufficiency occurs in a minority of patients with Takayasu aortitis,“.” and is usually attributed to annuloaortic ectasia, as was present in our case. Severe aortic insufficiency is infrequent.” and the clinical presentation of aortic insufficiencv as the sole manifestation of Takayasu aortitis is rare.’ ’ The presence of a giant cell granulomatous aortitis in a patient with aortic insufficiency without the classical clinical features of Takayasu aortitis should not preclude the diagnosis, especially in a young woman. irrespective of ethnic origin.
L
GASTRIC
ANTRAL
VASCULAR
ECTASlA
‘~.WLJI T.AN.AL~. MD, YOSHIO MOKI, MD, YLWO MORISHITA, MD, TOSHIHIRO KOJIM~Z,MD, TOSHIHIIW K~~W,UJOKI,MD. K,ULX) ASIANO, MD, M.C.~YOSHI ICHIHAR,~, MD, M.~crro
TAKAO. MD, AKIHIK~ &TOH,
.A IUC o/ga.s/rrc autml vasrular rrtasia corzfincd to the antrum in an elderly Ja,bnnr~ mle patient is described. The condition is a cause of t&d 10s.~ and chronic iron deJiciency anemia, particularly in the elderly. The clinical. endosropic, and pathologic findings. which were coutractrd with other h@erplastic or gastric zmcular ore described. -HrFnr PATHOL 22:1053abnormalities. 105 5, O’opyrl,qht 168199 I 1)~ B’.H. Saunders C.knpa?q
Volume 22, No. 10 (October
ADDENDUM
squamous carcinoma may be a collision tumor and that the squamous component may have developed from squamous metaplasia following radiation or hormonal therapy. Moyana’ and Lager et al’ propose that the adenosquamous carcinoma of the prostate is derived from resident pluripotent stem cells capable of multidirectional differentiation. This report supports the existence of a pluripotent stem cell that, following appropriate stimuli (such as irradiation or estrogen therapy), alters its line of differentiation. The altered differentiation may account for the lack of expression of “normal” prostatic antigens (PAP and PSA) in the metaplastic and malignant squamous cells. The squamous component in this case, although appearing well differentiated by light microscopy, shows no specific ultrastructural features of either an adenocarcinoma or a squamous cell carcinoma. As an aneuploid peak was not identified in either malignant component by flow cytometry or image analysis, the presence of two separate tumors differentiating from a pluripotent stem cell is neither supported nor overruled.
Since this paper was accepted for publication, Wernert et al7 have described two cases of prostatic adenocarcinoma with a malignant squamous component occurring after estrogen treatment. They suggest that the basal cells of the prostatic gland, in which they have identified nuclear estrogen receptors, undergo squamous metaplasia in response to estrogen treatment, and suggest that this may be a precursor of the malignant squamous component. The authors thank Saundra Dalton for typing Acknowkdgmen~ the manuscript, and the Audio-Visual Department, Royal College of Surgeons in Ireland, for photographic assistance.
REFERENCES 1. Green LF, Mulcahy JJ, Warren MM, et al: Primary transitional cell carcinoma of the prostate. J Ural 110:235-237. 1973 2. Saito R. Davis BK, Ollapally EP: Adenosquamous carcinoma of the prostate. HUM PATHOI. 15:87-89, 1984 3. Lager DJ, Goeken JA. Kemp JD, et al: Squamous metaplasia (>f the prostate-An immunohistochemical study. Am J Clin Pathol 90:597-601. 1988 4. Bainborough AR: Squamous metaplasia uf prostate following oestrogell therapy. J Ural 68:329-336. 1952 5. Bennett RS. Edgerton EO: Mixed prostatic carcinoma. J L’rol I l&561563, 1973 6. Moyana TN: Adenosquamous carcinoma of the prostate. Am J Surg Pathol 11:403-407. 1987 7. Wernert N, Goebbels R, Bonkhoff H, et al: Squamous cell carcirloma of the prostate. Histopathology 17:339-344, 1990
CONCLUSION In conclusion, despite the common occurrence of mixed types of carcinomas in other sites such as the lung, adenosquamous carcinoma of the prostate is exceedingly rare with, including this report, only four documented cases in the world literature. Estrogen therapy, being administered in three cases, may be implicated in the development of these unusual mixed tumors.
GRANULOMATOUS AORTIC IN TAKAYASU AORTITIS LYNDA
RUSHING,
MD,
FREDERICK
From the Departments
VALVULITIS
of Pathology
ASSOCIATED
MD, PHD,
J. SCHOEN,
and Vascular
ALAN
Medicine,
Brigham and Women’s Hospital, Boston, MA; and the Department
of Pathology, Mayo Clinic Foundation, oublication December 10. 1990. *Present address: Cardiovascular
nesota, Minneapolis, MN.
Rochester,
MN. Accepted
for
Division, University of Min-
1991)
WITH
HIRSCH,*
AORTIC
MD,
INSUFFICIENCY
AND J. T. LIE,
MD
We report an unusual CUSPof Takayasu aortitis associated with a giant cell granulomatous ualvulitis presenting with aortic ins@ciency. Although nonspecific valuular abnormalities have been reported with Takayasu aortitis, this case is the first to describe inuolvemxnt of the aortir valve by the disease. HLL~PATHOI. 22: 10501053. Copyright 0 1991 by W. B. Saunders Company
Key words: aortitis,
valvulitis, Takayasu aortitis. Address correspondence and reprint requests to Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women’s
Hospital, 75 Francis St, Boston, MA 02115. Copyright 0 1991 by W.B. Saunders Company 0046-8177/91/2210-0015$5,00/O
Takayasu aortitis is an inflammatory vascular disease of uncertain etiology. Classically. this disorder affects young women, usually of Asian descent, diminished pulses, hypertension.
1050
who present with absent or or claudication.’ Other, less
CASE STUDIES
FIGURE 1. Aorta. (Top) Low-power photomicrogroph of an aorta demonstrating disruption of medial elastic fibers and thickenNed intima and adventitia. The luminal surface is at the top. (Elastin stain; magrlification X40.) (Bottom) High-power view of aortic media with a lymphohistiocytic infiltrate and a multinucleated giant cell. (Hematoxylineosin stain; magnification X 140.)
common clinical presentations of the disease have been described, such as rupture and dissection of the thoracic aorta’ and coronary ischemia.“,’ Aortic insufficiency as a presenting clinical feature in Takayasu aortitis is unusual.“,” The patient reported here had aortic insufficiency as the initial manifestation of Takayasu aortitis. associated with the unique finding of granulomatous aortic valvulitis. REPORT
OF
24 CASE
A 3+year-old for elective aortic
white woman was admitted to the hospital valve rrplacement. Aortic insufficiency was
noted 6 years earlier at the time of her second pl-egnancv. Present symptoms included onl\ a sense of “prominent pt;lsations” in her neck. She specificallv denied fever. malaise. weight loss. arm or leg claudication. prior rheumatic fever, OI a family history of congenital heart disease. There was no history of hypertension. Phystcal examination, echoc;lrdiogr;lph); with doppler cxamination, and cardiac catheterization demonstrated severe aortic insufficiency, annuloaortic ectasia (aortic. I-oot cliametrr. 5.6 cm; normal, 2 to 3 cm). left ventricular enlargement with mildly decreased function, and normal coronan artc.rics. Ka-
1051
HUMAN PATHOLOGY
Volume 22, No. 10 (October
1991)
FIGURE 2. Aortic valve. (Top) Lowpower photomicrograph demon ,strating superficial and deep granul omatous inflammation of the aortic Ltalve. (Hematoxylin-eosin stain; magr lification x150.) (Bottom) Higher-p Newer view demonstrating giant cells. (Hematoxylin-eosin stain; magnitic ation X375.)
diai, femoral, and pedal pulses were normal. There were no flank or abdominal bruits. She underwent elective replacement of the aortic valve and ascending aorta by a valved conduit without complications. PATHOLOGIC
FINDINGS
Microscopic examination of the ascending aorta revealed a thickened intima, focal attenuation, and degeneration of the media, with loss of smooth muscle and elastic elements and
focal medial infarcts (Fig 1). The adventitia was thickened and there was transmural loss of elastic elements in some areas. Active inflammation was present in all three layers and appeared to consist of predominantly mononuclear cells with lymphocytes, histiocytes, and giant cells. In occasional areas where the aortic wall was largely intact, there was no cystic medial degeneration or other abnormality noted. Special stains for spirochetal, fungal, and bacterial organisms were negative. Histologic sections through the aortic valve revealed an active valvulitis extending from and morphologically similar
1052
CASE STUDIES to the aortic disease. There was a dense mononuclear infiltrate, composed predominantly of lymphocytes with focal neutrophils and hi.stiocytes and occasional giant cells (Fig 2). The uninvolved portions of the \-alve contained areas of intimal proliferation1 and myxomatous change. DISCUSSION The unique feature of this case is the presence of a giant cell granulomatous valvulitis in association with the aortitis. which, to our knowledge, has not been previously described in Takayasu aortitis. A report by Saito et al’ of five autopsied cases oi “aortitis syndrome” described a diffuse round cell infiltrate in the aortic. valve of one of the patients. The infiltrate was described as being present from the subendothelium to the media; hl)wever, there was no mention of a granulomatous component. Other reports’,’ of valvular abnormalities in Takayasi’s disease described a nonspecific fibrosis with or without mononuclear cells. A recent report’” described a patient with Reiter’s syndrome who had a severe giant cell valvulitis of both mitral and aortic valves with an otherwise nongranulomatous aor-titis. To our knowledge, this is the only other previous report of giant cell granulomatous valvulitis. The difrerential diagnosis of giant cell granulomatous aortitis includes syphilitic aortitis and giant cell arteritis, which can be morpholo@cally indistinguishable from Takayasu aortitis.” Takdyasu aortitis has also been described in association with systemic rheumatologic diseases such as rheumatoid arthritis, ankylosing spondylitis, and progressive systemic sclerosis.“,” Although thr patient reported here may have an underlying rheumatologic disorder that has yet to become overt, the oresence of all underlvincr disease does not exclude the diagLosis of Takayasu aortitis.Y Moreover, both syphilitic and tenlporal giant cell arteritis are unlikely possibilities, in view of the patient’s age and the clinical setting. The patient was
young and had no other stigmata commonly associated with syphilitic or temporal giant cell arteritis. Finally, aortir insufficiency occurs in a minority of patients with Takayasu aortitis,“.” and is usually attributed to annuloaortic ectasia, as was present in our case. Severe aortic insufficiency is infrequent.” and the clinical presentation of aortic insufficiencv as the sole manifestation of Takayasu aortitis is rare.’ ’ The presence of a giant cell granulomatous aortitis in a patient with aortic insufficiency without the classical clinical features of Takayasu aortitis should not preclude the diagnosis, especially in a young woman. irrespective of ethnic origin.
L
GASTRIC
ANTRAL
VASCULAR
ECTASlA
‘~.WLJI T.AN.AL~. MD, YOSHIO MOKI, MD, YLWO MORISHITA, MD, TOSHIHIRO KOJIM~Z,MD, TOSHIHIIW K~~W,UJOKI,MD. K,ULX) ASIANO, MD, M.C.~YOSHI ICHIHAR,~, MD, M.~crro
TAKAO. MD, AKIHIK~ &TOH,
.A IUC o/ga.s/rrc autml vasrular rrtasia corzfincd to the antrum in an elderly Ja,bnnr~ mle patient is described. The condition is a cause of t&d 10s.~ and chronic iron deJiciency anemia, particularly in the elderly. The clinical. endosropic, and pathologic findings. which were coutractrd with other h@erplastic or gastric zmcular ore described. -HrFnr PATHOL 22:1053abnormalities. 105 5, O’opyrl,qht 168199 I 1)~ B’.H. Saunders C.knpa?q
