484
ANATOMIC PATHOLOGY Single Case Reports
Psammomatous Melanotic Schwannoma: An Additional Component of Carney's Complex Report of a Case DAVID G. MARTIN-REAY, M.B., B.S., MARCIA C. SHATTUCK, M.D., AND FRANK W. GUTHRIE, JR., M.D.
previous history and pathologic material further supported the diagnosis. The authors conclude that recognition of each component as part of the syndrome is of crucial importance, because it may prevent a fatal outcome. A family screening program should be performed in each case. (Key words: Carney's complex; Psammomatous melanotic schwannoma; Cardiac myxoma; Bilateral primary pigmented, nodular, adrenocortical hyperplasia) Am J Clin Pathol 1991;95:484-489
A constellation of specific pathologic findings with dominant inheritance has been described by Carney and associates.1 This syndrome has been termed "Carney's complex" by others2 who have recognized similar cases. These abnormalities include the following:
reported as isolated lesions on several occasions4"16 and, infrequently, they have possessed calcifications.9"'214 Recently, Carney has shown that psammoma bodies (concentrically laminated calcifications) are a specific pathologic feature in these spindle cell tumors, and as such are strongly associated with the complex that bears his name.17 In this institution, a melanotic schwannoma was recently identified, within which there were several scattered psammoma bodies. Subsequent clinical evaluation of the patient and review of pathologic material were diagnostic of Carney's complex.
1. Bilateral primary pigmented, nodular, adrenocortical hyperplasia, 2. Multiple lentigines, particularly of the head and neck, and blue nevi, 3. Cutaneous myxomata, 4. Large-cell calcifying Sertoli's cell tumors of the testis, 5. Cardiac myxomata, 6. Myxoid fibroadenomas of the breast, and 7. Pituitary tumors
REPORT OF A CASE
The patient was a 32-year-old white man with a previous medical history of bilateral tumors of the testes at age 5, diagnosed as embryonal carcinoma and treated with bilateral orchiectomy, pelvic lymphadenectomy, and radiation therapy. Pathologic material was unavailable for review. At age 17, he was investigated for growth failure and was discovered to have Cushing's syndrome. Endocrine investigations, including iodocholesterol scanning, were consistent with bilateral nodular adrenal From the Departments of Pathology and Medicine, The Evanston hyperplasia, and he was successfully treated for three years with o,p'Hospital, Evanston, Illinois. dichloro-diphenyldichloroethane (o.p'DDD), which is a selective adrenal toxin.18 Serial clinical and biochemical follow-up has not revealed eviReceived March 27, 1990; received revised manuscript and accepted dence of recurrent Cushing's syndrome. At age 27, he had an unexplained for publication September 7, 1990. myocardial infarct. Cardiac catheterization showed normal coronary arAddress reprint requests to Dr. Martin-Reay: Department of Pathology teries. There was no evidence of a cardiac myxoma. Several cutaneous and Laboratory Medicine, The Evanston Hospital, 2650 North Ridge lesions were removed seven years before the most recent admission. Avenue, Evanston, Illinois 60201.
Other authors3 have described a similar dominantly inherited syndrome with the additional finding of a melanotic schwannoma. Melanotic schwannomas have been
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The authors report a case of Carney's complex (the complex of myxomas, spotty pigmentation, and endocrine overactivity) in a 32-year-old white man. Psammomatous melanotic schwannoma has recently been included as a component of this disorder. The complex was recognized after a psammomatous melanotic schwannoma was resected from the sacral canal. Subsequent echocardiography revealed ventricular cardiac myxomata. Resection of these lesions was successfully performed. Review of
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Psammomatous Melinotic Schwannoma
PATHOLOGIC FINDINGS
The sacral tumor consisted of several portions of irregularly shaped, black soft tissue measuring approximately 3.0 X 2.5 X 1.5 cm in aggregate. Microscopically, the tumor was heavily pigmented. The pigment consisted of numerous aggregates of coarse, brown granules. Scattered throughout were several purple-staining, laminated, round, psammoma bodies (Fig. AA). The tumor itself consisted of spindle cells that were arranged into densely cellular (Antoni A) and loosely cellular (Antoni B) areas. The spindle cells demonstrated significant palisading, forming Verocay bodies. There was considerable necrosis. Mild nuclear atypia was identified, but mitotic figures were not prominent. The pigment granules did not stain with iron stains but bleached with acidified potassium permanganate ("melanin bleach reaction"), thus demonstrating that the pigment was, indeed, melanin (Fig. AB). Staining for S-100 antigen, a marker for Schwann's cells, was positive with the use of standard immunoperoxidase techniques (Biomeda Corporation). Review of the pathologic material removed from the skin seven years previously showed two interesting pathologic entities. Two lesions around the left nipple and one from the left groin had similar features. Both lesions at the nipple were pink-tan, well circumscribed, and lobulated. Each measured less than 1.0 cm in greatest dimension. One contained glistening mucinous material on cut
section. Histologically, both showed dermal and subcutaneous deposition of myxoid material that stained positively for colloidal iron and was digested by hyaluronidase, proving that it was composed of proteoglycans, predominantly hyaluronic acid. Thus, they were diagnostic of cutaneous myxomata. Second, a pigmented lesion located on the right arm was composed of dendritic intradermal melanocytes typical of a blue nevus. The cardiac lesions were composed of myxoid stroma, which was fiscally degenerating and contained scattered stellate and spindle cells characteristic of myxomata. Review of the surgical pathology report of the patient's orchiectomy specimens revealed that the testicular tumors contained numerous calcified nodules. DISCUSSION A series of reports has documented the existence of Carney's complex.'" 31719 '" 23 The components include cardiac, cutaneous, and mammary myxomatous masses; spotty pigmented skin lesions (lentigines and blue nevi); endocrine disorders (primary pigmented, nodular adrenocortical disease and pituitary tumors); and testicular tumors (usually of the large-cell calcifying Sertoli's cell type). The involvement of organs is often multicentric and bilateral and usually occurs in young patients. The possibility that this is a hereditary disorder is suggested by the occurrence of several of these disorders within families. A tentative diagnosis of this "complex" should be made if two of these conditions are present and a definitive diagnosis made if there are three or more. Carney and associates' have concluded that the complex is dominantly inherited, and this has been confirmed by Bain2 with the detection of the condition in both father and son. In the current case report, a definitive diagnosis of Carney's complex can be made because of a history of bilateral calcifying testicular tumors; Cushing's syndrome secondary to bilateral nodular adrenocortical hyperplasia; a blue nevus; spotty pigmentation of the head, neck, and conjunctiva; several cutaneous myxomata; and a pituitary lesion seen on CT scan. The pathologic diagnoses of psammomatous melanotic schwannoma and unusually situated cardiac myxomata add additional support to the diagnosis. Although the association of embryonal carcinoma has not been reported, the pathologic material from the testicular tumors was not available for review and specific histopathologic features cannot be confirmed. However, the described calcifications are highly suggestive of large-cell calcifying Sertoli's cell tumors. Melanotic schwannoma is an uncommon entity that was first described by Bjorneboe in 1934.5 The lesion has an equal sex ratio and a mean patient age at diagnosis of 38 years.9 Initial reports regarding its natural history were
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To date, there is no family history of cutaneous lesions, endocrine abnormalities, or myxomata in siblings or parents. The patient receives testosterone injections. At his last presentation, he complained of sudden onset of left buttock and coccygeal pain made worse by sitting. He had no history of recent trauma. Examination showed a white man of short stature. The skin and mucous membranes revealed focal pigmented lesions distributed over the head and neck; one of these was present on the semilunar fold of the conjunctiva (Fig. M). Additionally, two small, raised skin lesions (thought to be cutaneous myxomata) were observed adjacent to the nipple (Fig. 1 iS). No neurologic deficits were observed. Cytogenetic studies revealed a normal male karyotype (46XY). Computed tomography (CT) scan of the sella turcica disclosed a clinically nonfunctional, abnormally enhanced, 0.4 cm X 0.7 cm lesion. Radioisotopic bone scan, pelvic tomography scan, and magnetic resonance imaging revealed a well-circumscribed large tumor within the sacral canal (Figs. 2/1 and 2B). Sacral laminectomy was performed, revealing a green-black tumor mass, apparently encapsulated, having an intimate association with nerve roots. The tumor measured 3.0 X 3.0 X 2.5 cm. The contents of the tumor capsule were evacuated and the capsule closed. The patient had an uneventful postoperative recovery. Postoperative echocardiogram and cardiac cine CT (Fig. 3A) were highly suggestive of two pedunculated cardiac myxomata originating from under a cusp of the mitral valve and prolapsing into the left ventricular chamber. Subsequent surgery demonstrated two pedunculated myxomata arising from the medial papillary muscles of the left ventricle (2.2 and 2.0 cm) (Fig. 3B). A third myxoma was discovered (0.4 cm) on the atrial surface of the mitral valve. All lesions were resected, and the mitral valve was repaired. The patient had a successful postoperative recovery.
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FIG. 1 (upper). A. Pigmentation of the semilunar fold of the conjunctiva (arrow). B. Well-circumscribed, lobulated, cutaneous myxomata at the areolar margin (arrow). FIG. 2 (lower). MRI scans of the sacrum sagittal (A) and coronal (B) section show a well-demarcated tumor (arrow) within the sacral canal, which prolapses into a sacral foramen.
guarded and suggestive of an aggressive potential. However, Lowman and Livolsi10 described two cases of spinal melanotic schwannoma with long-term freedom from tumor recurrence after resection. A recent study reported a recurrence rate of 24%.9 Several reports have described these tumors in the spinal canal, 4 , 8 1 0 "' 3 1 5 the most frequent location being the spinal nerve roots.9 The melanin present in these neoplasms is known to be a product of the Schwann's cell.13
Danoff and associates3 were the first to describe melanotic schwannomas within a family. These tumors exclusively involved the gastrointestinal tract. The authors do not make reference to psammoma body formation. The psammomatous melanotic schwannoma cases described by Carney17 that are associated with the complex may occur in several locations, including spinal nerve roots, alimentary tract, and bone. The differential diagnosis of melanotic lesions of the
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Psammomatous Melanotic Schwannoma
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FIG. 3 (upper). A. Cardiac cine CT scan illustrating two pedunculated cardiac myxomata within the left ventricle (arrows). B. Resected cardiac myxomata from the left ventricle. The tumors have a markedly gelatinous appearance. FIG. 4 (lower). A. Psammomatous melanotic schwannoma showing laminated round calcification; psammoma body (lower center), densely (Antoni A) and loosely (Antoni B) cellular areas with coarse melanin pigment. Hematoxylin and eosin (X200). B. Following treatment with acidified potassium permanganate. The tumor demonstrates zonal nuclear palisading (Verocay bodies) typical of a schwannoma. Hematoxylin and eosin (X400).
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nervous system includes diffuse or focal leptomeningeal melanosis, melanotic meningioma, primary malignant melanoma of the central nervous system, and melanotic schwannoma. Metastatic malignant melanoma is the most common lesion and, therefore, a primary cutaneous, mucosal, or ocular site must be sought. The diagnosis of melanotic schwannoma may be made confidently once the cellular pattern is clarified by removal of heavy melanin pigmentation. The typical histologic pattern generally will then be evident. The diagnosis also may be facilitated by the use of immunoperoxidase techniques and electron microscopic examination.
The cutaneous myxomatous masses seen in this syndrome also have several characteristic features that are similar to those of our case.20 They are multicentric (71% of patients), are usually small (less than 1.0 cm), and have a predilection for certain sites, particularly the nipples, ears, and eyelids. However, they may be widespread. Histologically, they are commonly in the dermis, subcutis, or both and often show circumscription and lobulation by delicate fibrous septae. They are significantly hypocellular and are composed of abundant proteoglycans, particularly hyaluronic acid. The cells within the mucinous matrix resemble fibroblasts. The cell of origin that has been suggested is that of the outer root sheath of the
Acknowledgments. The authors thank Dr. J. A. Carney, M.D., for reviewing some of the pathologic material, Lynda Alterio for typing the manuscript, Pat Redden for the illustrations, and Tess Anton for library services.
REFERENCES 1. Carney JA, Hruska LS, Beauchamp GD, Gordon H. Dominant inheritance of the complex of myxomas, spotty pigmentation, and endocrine overactivity. Mayo Clin Proc 1986;61:165-172. 2. Bain J. "Carney's complex"[Letter]. Mayo Clin Proc 1986;61:508. 3. Danoff A, Jormark S, Lorber D, Fleischer N. Adrenocortical micronodular dysplasia, cardiac myxomas, lentigines, and spindle cell tumors. Arch Intern Med 1987;147:443-448. 4. Bagchi AK, Sarkar SK, Chakraborti DP, Roy CK. Melanotic spinal schwannoma. Surg Neurol 1975;3:79-81. 5. Bjorneboe M. Primares Melanosarkom des Gehirns, massenhafte Naevi pigmentosi der Haut, ausgedehnte Neurofibromatose der Hautnerven. Frankfurter Zeitschrift fur Pathologie 1934;47:363373. 6. Dastur DK, Sinh G, Pandya SK. Melanotic tumor of the acoustic nerve. J Neurosurg 1967;27:166-170. 7. Di Gregorio C, Fano RA, Criscuolo M. Melanotic schwannoma: a case report. Appl Pathol 1984,2:110-115. 8. Gregorios JB, Chou SM, Bay J. Melanotic schwannoma of the spinal cord. Neurosurgery 1982; 11:57-60. 9. Kileen RM, Davy CL, Bauserman SC. Melanocytic schwannoma. Cancer 1988;62:174-183. 10. Lowman RM, Livolsi VA. Pigmented (melanotic) schwannomas of the spinal canal. Cancer 1980;46:391-397. 11. McGavran WL III, Sypert GW, Ballinger WE. Melanotic schwannoma. Neurosurgery 1978;2:47-51. 12. Meier RJ, Altermatt HJ, Musy JP, Gebbers JO. Melanotisches Schwannom. Pathologe 1987;8:282-290. 13. Mennenmeyer RP, Hammar SP, Tytus JS, Hallman KO, Raisis JE, Bockus D. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 1979;3:3-10. 14. Parent M, Beyls-Noel I, Lecomte-Houcke M, Fontaine C, Dupont A. Schwannome Melanotique. Arch Anat Cytol Pathol 1987;35: 76-81. 15. Paris F, Cabanes J, Munoz C, Tamarit L. Melanotic spinothoracic schwannoma. Thorax 1979;34:243-246. 16. Shillitoe AJ. Melanotic schwannoma. J Pathol Bacteriol 1965;90: 667-668. 17. Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 1990; 14: 206-222. 18. Luton JP, Mahoudeau JA, Bouchard PH, et al. Treatment of Cushing's disease by o.p'DDD. N Engl J Med 1979;300:459-464.
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The diagnosis of psammomatous melanotic schwannoma is of particular clinical importance as it emerges as one of the components of a syndrome that may result in serious or fatal consequences if not detected early. Fatal consequences, including embolization of cardiac myxoma, have occurred in 25% of reported cases.21 SchweizerCaigianut and associates22 state that familial cardiac myxomata tend to be papillary and friable and are capable of giving rise to multiple infarcts, as occurred in two of their reported cases. A tumor embolus may explain the occurrence of myocardial infarct in this patient at such a young age because cardiac myxomata may be very small24 and go unrecognized on cardiac catheterization. The recognition of the clinical syndrome in our case enabled left ventricular and valvular cardiac myxomata to be identified. Moreover, family screening is being performed and, although additional cases have not yet been discovered, future generations will require careful follow-up. The underlying mechanism of this multicentric disorder is unknown and requires considerable additional investigation. Cytogenetic studies performed on a few individual cases have demonstrated a normal karyotype, as did studies on our patient.' ,2225 This is to be expected because a pattern of autosomal dominant inheritance suggests a single gene defect. Because it has not been detected in another family member in this case, this condition may also result from a spontaneous mutation.
hair follicle because a number of the myxomas have been perifollicular or exhibited trichoblastic proliferations. However, myxomata also have occurred in an intraoral location that this hypothesis cannot explain.21 In conclusion, we have illustrated a remarkable case incorporating virtually all the features that are pathognomonic for Carney's complex. The clinical and pathologic identification of this syndrome permitted the surgical correction of potentially lethal cardiac lesions and emphasized the necessity of careful patient follow-up. Attention must be paid to continued family surveillance for additional cases.
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Psammomatous Melanotic Schwannoma 19. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VLW. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985;64:270-283. 20. Carney JA, Headington JT, Su WPD. Cutaneous myxomas. A major component of the complex of myxomas, spotty pigmentation and endocrine overactivity. Arch Dermatol 1986;122:790-798. 21. Cook CA, Lund BA, Carney JA. Mucocutaneous pigmented spots and oral myxomas: the oral manifestations of the complex of myxomas, spotty pigmentation and endocrine overactivity. Oral Surg Oral Med Oral Pathol 1987;63:175-183. 22. Schweizer-Cagianut M, Salomon F, Hedinger CE. Primary adre-
nocortical nodular dysplasia with Cushing's syndrome and cardiac myxomas. A peculiar familial disease. Virchows Arch [A] 1982;397:183-192. 23. Shennoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing's syndrome. Am J Surg Pathol 1984;8:335-344. 24. Vatterott PJ, Seward JB, Vidaillet JH, Su WPD, Oftedahl GL. Syndrome cardiac myxoma: more than just a sporadic event. Am Heart J 1987;114:886-889. 25. Proppe KH, Scully RE. Large-cell calcifying Sertoli cell tumor of the testis. Am J Clin Pathol 1980;74:607-619.
MARGARET V. RAGNI, M.D., ANDREW DEKKER, M.D., FREDERICK R. D E R U B E R T I S , M.D., CHARLES G. WATSON, M.D., M. LEON SKOLNICK, M.D., SUSAN D. GOOLD, M.D., MICHAEL W. FINIKIOTIS, M.D., SALIL DOSHI, M.D., AND DELYNNE J. MYERS, M.D.
Extrapulmonary Pneumocystis infection has been increasingly reported in patients with acquired immune deficiency syndrome (AIDS), in particular, recently in association with the increasing use of aerosolized pentamidine. This report describes the unusual presentation of extrapulmonary Pneumocystis infection as a thyroid neck mass and clinical hypothyroidism in a 37-year-old man with hemophilia and AIDS. This case differs from the previously reported single case of isolated thyroid pneumocystosis in the presence of a rapidly enlarging neck mass, lack of previous Pneumocystis, and prior prophylaxis with aerosolized pentamidine. The pathologic and electron microscopic description of the
peculiar flocculent necrotic thyroid material is contrasted with typical pulmonary alveolar findings in Pneumocystis pneumonia (PCP), the differential diagnoses of a rapidly expanding neck mass, and diagnostic difficulties of hypothyroidism in patients with AIDS are discussed. Finally, it is emphasized that use of aerosolized pentamidine, although successful for prevention of pulmonary PCP, may be insufficient to prevent extrapulmonary infection. (Key words: Pneumocystis carinii pneumonia |PCPJ; Acquired immune deficiency syndrome (AIDS); Extrapulmonary pneumocystosis; Thyroid mass) Am J Clin Pathol 199I;95: 489-493
Despite advances in treatment and prophylaxis, Pneumocystis carinii pneumonia (PCP) continues to be the most c o m m o n opportunistic infection reported in patients with acquired immune deficiency syndrome (AIDS), with more than 60% of patients with AIDS presenting with PCP and another 20% having PCP as a later diagnosis.1,2 Although PCP is regarded as a primary pulmonary pathogen, there have been increasing reports of extrapulmonary
Pneumocystis infection.3"5 These may relate, in part, to the recent introduction of aerosolized pentamidine, 6 which, with only minimal systemic absorption,7 promotes eradication of pulmonary Pneumocystis while allowing unchecked development of nonpulmonary Pneumocystis. Recently we cared for a patient with hemophilia and AIDS who presented with an acute diffuse goiter, hypothyroidism, and P. carinii of the thyroid.
REPORT OF A CASE From the Departments ofMedicine. Radiology, Surgery, and Pathology, University of Pittsburgh School ofMedicine, and the Hemophilia Center A 37-year-old man with severe hemophilia A (< 0.01 U/mL Factor of Western Pennsylvania, Pittsburgh, Pennsylvania. VIII:C) and AIDS presented in July 1989 with a painful right neck mass and transient dysarthria. There had been no trauma. Ultrasound revealed Received March 8, 1990; received revised manuscript and accepted the mass to be an enlarged right lobe of the thyroid, with echogenic areas for publication April 5, 1990. consistent with calcification and suggestive of hematoma. The left lobe Address reprint requests to Dr. Ragni: Hemophilia Center of Western appeared normal. Treatment with Factor VIII concentrate therapy rePennsylvania, 812 Fifth Avenue, Pittsburgh, Pennsylvania 15219.
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Pneumocystis carinii Infection Presenting as Necrotizing Thyroiditis and Hypothyroidism
ANATOMIC PATHOLOGY Single Case Reports
Psammomatous Melanotic Schwannoma: An Additional Component of Carney's Complex Report of a Case DAVID G. MARTIN-REAY, M.B., B.S., MARCIA C. SHATTUCK, M.D., AND FRANK W. GUTHRIE, JR., M.D.
previous history and pathologic material further supported the diagnosis. The authors conclude that recognition of each component as part of the syndrome is of crucial importance, because it may prevent a fatal outcome. A family screening program should be performed in each case. (Key words: Carney's complex; Psammomatous melanotic schwannoma; Cardiac myxoma; Bilateral primary pigmented, nodular, adrenocortical hyperplasia) Am J Clin Pathol 1991;95:484-489
A constellation of specific pathologic findings with dominant inheritance has been described by Carney and associates.1 This syndrome has been termed "Carney's complex" by others2 who have recognized similar cases. These abnormalities include the following:
reported as isolated lesions on several occasions4"16 and, infrequently, they have possessed calcifications.9"'214 Recently, Carney has shown that psammoma bodies (concentrically laminated calcifications) are a specific pathologic feature in these spindle cell tumors, and as such are strongly associated with the complex that bears his name.17 In this institution, a melanotic schwannoma was recently identified, within which there were several scattered psammoma bodies. Subsequent clinical evaluation of the patient and review of pathologic material were diagnostic of Carney's complex.
1. Bilateral primary pigmented, nodular, adrenocortical hyperplasia, 2. Multiple lentigines, particularly of the head and neck, and blue nevi, 3. Cutaneous myxomata, 4. Large-cell calcifying Sertoli's cell tumors of the testis, 5. Cardiac myxomata, 6. Myxoid fibroadenomas of the breast, and 7. Pituitary tumors
REPORT OF A CASE
The patient was a 32-year-old white man with a previous medical history of bilateral tumors of the testes at age 5, diagnosed as embryonal carcinoma and treated with bilateral orchiectomy, pelvic lymphadenectomy, and radiation therapy. Pathologic material was unavailable for review. At age 17, he was investigated for growth failure and was discovered to have Cushing's syndrome. Endocrine investigations, including iodocholesterol scanning, were consistent with bilateral nodular adrenal From the Departments of Pathology and Medicine, The Evanston hyperplasia, and he was successfully treated for three years with o,p'Hospital, Evanston, Illinois. dichloro-diphenyldichloroethane (o.p'DDD), which is a selective adrenal toxin.18 Serial clinical and biochemical follow-up has not revealed eviReceived March 27, 1990; received revised manuscript and accepted dence of recurrent Cushing's syndrome. At age 27, he had an unexplained for publication September 7, 1990. myocardial infarct. Cardiac catheterization showed normal coronary arAddress reprint requests to Dr. Martin-Reay: Department of Pathology teries. There was no evidence of a cardiac myxoma. Several cutaneous and Laboratory Medicine, The Evanston Hospital, 2650 North Ridge lesions were removed seven years before the most recent admission. Avenue, Evanston, Illinois 60201.
Other authors3 have described a similar dominantly inherited syndrome with the additional finding of a melanotic schwannoma. Melanotic schwannomas have been
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
The authors report a case of Carney's complex (the complex of myxomas, spotty pigmentation, and endocrine overactivity) in a 32-year-old white man. Psammomatous melanotic schwannoma has recently been included as a component of this disorder. The complex was recognized after a psammomatous melanotic schwannoma was resected from the sacral canal. Subsequent echocardiography revealed ventricular cardiac myxomata. Resection of these lesions was successfully performed. Review of
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Psammomatous Melinotic Schwannoma
PATHOLOGIC FINDINGS
The sacral tumor consisted of several portions of irregularly shaped, black soft tissue measuring approximately 3.0 X 2.5 X 1.5 cm in aggregate. Microscopically, the tumor was heavily pigmented. The pigment consisted of numerous aggregates of coarse, brown granules. Scattered throughout were several purple-staining, laminated, round, psammoma bodies (Fig. AA). The tumor itself consisted of spindle cells that were arranged into densely cellular (Antoni A) and loosely cellular (Antoni B) areas. The spindle cells demonstrated significant palisading, forming Verocay bodies. There was considerable necrosis. Mild nuclear atypia was identified, but mitotic figures were not prominent. The pigment granules did not stain with iron stains but bleached with acidified potassium permanganate ("melanin bleach reaction"), thus demonstrating that the pigment was, indeed, melanin (Fig. AB). Staining for S-100 antigen, a marker for Schwann's cells, was positive with the use of standard immunoperoxidase techniques (Biomeda Corporation). Review of the pathologic material removed from the skin seven years previously showed two interesting pathologic entities. Two lesions around the left nipple and one from the left groin had similar features. Both lesions at the nipple were pink-tan, well circumscribed, and lobulated. Each measured less than 1.0 cm in greatest dimension. One contained glistening mucinous material on cut
section. Histologically, both showed dermal and subcutaneous deposition of myxoid material that stained positively for colloidal iron and was digested by hyaluronidase, proving that it was composed of proteoglycans, predominantly hyaluronic acid. Thus, they were diagnostic of cutaneous myxomata. Second, a pigmented lesion located on the right arm was composed of dendritic intradermal melanocytes typical of a blue nevus. The cardiac lesions were composed of myxoid stroma, which was fiscally degenerating and contained scattered stellate and spindle cells characteristic of myxomata. Review of the surgical pathology report of the patient's orchiectomy specimens revealed that the testicular tumors contained numerous calcified nodules. DISCUSSION A series of reports has documented the existence of Carney's complex.'" 31719 '" 23 The components include cardiac, cutaneous, and mammary myxomatous masses; spotty pigmented skin lesions (lentigines and blue nevi); endocrine disorders (primary pigmented, nodular adrenocortical disease and pituitary tumors); and testicular tumors (usually of the large-cell calcifying Sertoli's cell type). The involvement of organs is often multicentric and bilateral and usually occurs in young patients. The possibility that this is a hereditary disorder is suggested by the occurrence of several of these disorders within families. A tentative diagnosis of this "complex" should be made if two of these conditions are present and a definitive diagnosis made if there are three or more. Carney and associates' have concluded that the complex is dominantly inherited, and this has been confirmed by Bain2 with the detection of the condition in both father and son. In the current case report, a definitive diagnosis of Carney's complex can be made because of a history of bilateral calcifying testicular tumors; Cushing's syndrome secondary to bilateral nodular adrenocortical hyperplasia; a blue nevus; spotty pigmentation of the head, neck, and conjunctiva; several cutaneous myxomata; and a pituitary lesion seen on CT scan. The pathologic diagnoses of psammomatous melanotic schwannoma and unusually situated cardiac myxomata add additional support to the diagnosis. Although the association of embryonal carcinoma has not been reported, the pathologic material from the testicular tumors was not available for review and specific histopathologic features cannot be confirmed. However, the described calcifications are highly suggestive of large-cell calcifying Sertoli's cell tumors. Melanotic schwannoma is an uncommon entity that was first described by Bjorneboe in 1934.5 The lesion has an equal sex ratio and a mean patient age at diagnosis of 38 years.9 Initial reports regarding its natural history were
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To date, there is no family history of cutaneous lesions, endocrine abnormalities, or myxomata in siblings or parents. The patient receives testosterone injections. At his last presentation, he complained of sudden onset of left buttock and coccygeal pain made worse by sitting. He had no history of recent trauma. Examination showed a white man of short stature. The skin and mucous membranes revealed focal pigmented lesions distributed over the head and neck; one of these was present on the semilunar fold of the conjunctiva (Fig. M). Additionally, two small, raised skin lesions (thought to be cutaneous myxomata) were observed adjacent to the nipple (Fig. 1 iS). No neurologic deficits were observed. Cytogenetic studies revealed a normal male karyotype (46XY). Computed tomography (CT) scan of the sella turcica disclosed a clinically nonfunctional, abnormally enhanced, 0.4 cm X 0.7 cm lesion. Radioisotopic bone scan, pelvic tomography scan, and magnetic resonance imaging revealed a well-circumscribed large tumor within the sacral canal (Figs. 2/1 and 2B). Sacral laminectomy was performed, revealing a green-black tumor mass, apparently encapsulated, having an intimate association with nerve roots. The tumor measured 3.0 X 3.0 X 2.5 cm. The contents of the tumor capsule were evacuated and the capsule closed. The patient had an uneventful postoperative recovery. Postoperative echocardiogram and cardiac cine CT (Fig. 3A) were highly suggestive of two pedunculated cardiac myxomata originating from under a cusp of the mitral valve and prolapsing into the left ventricular chamber. Subsequent surgery demonstrated two pedunculated myxomata arising from the medial papillary muscles of the left ventricle (2.2 and 2.0 cm) (Fig. 3B). A third myxoma was discovered (0.4 cm) on the atrial surface of the mitral valve. All lesions were resected, and the mitral valve was repaired. The patient had a successful postoperative recovery.
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FIG. 1 (upper). A. Pigmentation of the semilunar fold of the conjunctiva (arrow). B. Well-circumscribed, lobulated, cutaneous myxomata at the areolar margin (arrow). FIG. 2 (lower). MRI scans of the sacrum sagittal (A) and coronal (B) section show a well-demarcated tumor (arrow) within the sacral canal, which prolapses into a sacral foramen.
guarded and suggestive of an aggressive potential. However, Lowman and Livolsi10 described two cases of spinal melanotic schwannoma with long-term freedom from tumor recurrence after resection. A recent study reported a recurrence rate of 24%.9 Several reports have described these tumors in the spinal canal, 4 , 8 1 0 "' 3 1 5 the most frequent location being the spinal nerve roots.9 The melanin present in these neoplasms is known to be a product of the Schwann's cell.13
Danoff and associates3 were the first to describe melanotic schwannomas within a family. These tumors exclusively involved the gastrointestinal tract. The authors do not make reference to psammoma body formation. The psammomatous melanotic schwannoma cases described by Carney17 that are associated with the complex may occur in several locations, including spinal nerve roots, alimentary tract, and bone. The differential diagnosis of melanotic lesions of the
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FIG. 3 (upper). A. Cardiac cine CT scan illustrating two pedunculated cardiac myxomata within the left ventricle (arrows). B. Resected cardiac myxomata from the left ventricle. The tumors have a markedly gelatinous appearance. FIG. 4 (lower). A. Psammomatous melanotic schwannoma showing laminated round calcification; psammoma body (lower center), densely (Antoni A) and loosely (Antoni B) cellular areas with coarse melanin pigment. Hematoxylin and eosin (X200). B. Following treatment with acidified potassium permanganate. The tumor demonstrates zonal nuclear palisading (Verocay bodies) typical of a schwannoma. Hematoxylin and eosin (X400).
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nervous system includes diffuse or focal leptomeningeal melanosis, melanotic meningioma, primary malignant melanoma of the central nervous system, and melanotic schwannoma. Metastatic malignant melanoma is the most common lesion and, therefore, a primary cutaneous, mucosal, or ocular site must be sought. The diagnosis of melanotic schwannoma may be made confidently once the cellular pattern is clarified by removal of heavy melanin pigmentation. The typical histologic pattern generally will then be evident. The diagnosis also may be facilitated by the use of immunoperoxidase techniques and electron microscopic examination.
The cutaneous myxomatous masses seen in this syndrome also have several characteristic features that are similar to those of our case.20 They are multicentric (71% of patients), are usually small (less than 1.0 cm), and have a predilection for certain sites, particularly the nipples, ears, and eyelids. However, they may be widespread. Histologically, they are commonly in the dermis, subcutis, or both and often show circumscription and lobulation by delicate fibrous septae. They are significantly hypocellular and are composed of abundant proteoglycans, particularly hyaluronic acid. The cells within the mucinous matrix resemble fibroblasts. The cell of origin that has been suggested is that of the outer root sheath of the
Acknowledgments. The authors thank Dr. J. A. Carney, M.D., for reviewing some of the pathologic material, Lynda Alterio for typing the manuscript, Pat Redden for the illustrations, and Tess Anton for library services.
REFERENCES 1. Carney JA, Hruska LS, Beauchamp GD, Gordon H. Dominant inheritance of the complex of myxomas, spotty pigmentation, and endocrine overactivity. Mayo Clin Proc 1986;61:165-172. 2. Bain J. "Carney's complex"[Letter]. Mayo Clin Proc 1986;61:508. 3. Danoff A, Jormark S, Lorber D, Fleischer N. Adrenocortical micronodular dysplasia, cardiac myxomas, lentigines, and spindle cell tumors. Arch Intern Med 1987;147:443-448. 4. Bagchi AK, Sarkar SK, Chakraborti DP, Roy CK. Melanotic spinal schwannoma. Surg Neurol 1975;3:79-81. 5. Bjorneboe M. Primares Melanosarkom des Gehirns, massenhafte Naevi pigmentosi der Haut, ausgedehnte Neurofibromatose der Hautnerven. Frankfurter Zeitschrift fur Pathologie 1934;47:363373. 6. Dastur DK, Sinh G, Pandya SK. Melanotic tumor of the acoustic nerve. J Neurosurg 1967;27:166-170. 7. Di Gregorio C, Fano RA, Criscuolo M. Melanotic schwannoma: a case report. Appl Pathol 1984,2:110-115. 8. Gregorios JB, Chou SM, Bay J. Melanotic schwannoma of the spinal cord. Neurosurgery 1982; 11:57-60. 9. Kileen RM, Davy CL, Bauserman SC. Melanocytic schwannoma. Cancer 1988;62:174-183. 10. Lowman RM, Livolsi VA. Pigmented (melanotic) schwannomas of the spinal canal. Cancer 1980;46:391-397. 11. McGavran WL III, Sypert GW, Ballinger WE. Melanotic schwannoma. Neurosurgery 1978;2:47-51. 12. Meier RJ, Altermatt HJ, Musy JP, Gebbers JO. Melanotisches Schwannom. Pathologe 1987;8:282-290. 13. Mennenmeyer RP, Hammar SP, Tytus JS, Hallman KO, Raisis JE, Bockus D. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 1979;3:3-10. 14. Parent M, Beyls-Noel I, Lecomte-Houcke M, Fontaine C, Dupont A. Schwannome Melanotique. Arch Anat Cytol Pathol 1987;35: 76-81. 15. Paris F, Cabanes J, Munoz C, Tamarit L. Melanotic spinothoracic schwannoma. Thorax 1979;34:243-246. 16. Shillitoe AJ. Melanotic schwannoma. J Pathol Bacteriol 1965;90: 667-668. 17. Carney JA. Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 1990; 14: 206-222. 18. Luton JP, Mahoudeau JA, Bouchard PH, et al. Treatment of Cushing's disease by o.p'DDD. N Engl J Med 1979;300:459-464.
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The diagnosis of psammomatous melanotic schwannoma is of particular clinical importance as it emerges as one of the components of a syndrome that may result in serious or fatal consequences if not detected early. Fatal consequences, including embolization of cardiac myxoma, have occurred in 25% of reported cases.21 SchweizerCaigianut and associates22 state that familial cardiac myxomata tend to be papillary and friable and are capable of giving rise to multiple infarcts, as occurred in two of their reported cases. A tumor embolus may explain the occurrence of myocardial infarct in this patient at such a young age because cardiac myxomata may be very small24 and go unrecognized on cardiac catheterization. The recognition of the clinical syndrome in our case enabled left ventricular and valvular cardiac myxomata to be identified. Moreover, family screening is being performed and, although additional cases have not yet been discovered, future generations will require careful follow-up. The underlying mechanism of this multicentric disorder is unknown and requires considerable additional investigation. Cytogenetic studies performed on a few individual cases have demonstrated a normal karyotype, as did studies on our patient.' ,2225 This is to be expected because a pattern of autosomal dominant inheritance suggests a single gene defect. Because it has not been detected in another family member in this case, this condition may also result from a spontaneous mutation.
hair follicle because a number of the myxomas have been perifollicular or exhibited trichoblastic proliferations. However, myxomata also have occurred in an intraoral location that this hypothesis cannot explain.21 In conclusion, we have illustrated a remarkable case incorporating virtually all the features that are pathognomonic for Carney's complex. The clinical and pathologic identification of this syndrome permitted the surgical correction of potentially lethal cardiac lesions and emphasized the necessity of careful patient follow-up. Attention must be paid to continued family surveillance for additional cases.
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Psammomatous Melanotic Schwannoma 19. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VLW. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985;64:270-283. 20. Carney JA, Headington JT, Su WPD. Cutaneous myxomas. A major component of the complex of myxomas, spotty pigmentation and endocrine overactivity. Arch Dermatol 1986;122:790-798. 21. Cook CA, Lund BA, Carney JA. Mucocutaneous pigmented spots and oral myxomas: the oral manifestations of the complex of myxomas, spotty pigmentation and endocrine overactivity. Oral Surg Oral Med Oral Pathol 1987;63:175-183. 22. Schweizer-Cagianut M, Salomon F, Hedinger CE. Primary adre-
nocortical nodular dysplasia with Cushing's syndrome and cardiac myxomas. A peculiar familial disease. Virchows Arch [A] 1982;397:183-192. 23. Shennoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing's syndrome. Am J Surg Pathol 1984;8:335-344. 24. Vatterott PJ, Seward JB, Vidaillet JH, Su WPD, Oftedahl GL. Syndrome cardiac myxoma: more than just a sporadic event. Am Heart J 1987;114:886-889. 25. Proppe KH, Scully RE. Large-cell calcifying Sertoli cell tumor of the testis. Am J Clin Pathol 1980;74:607-619.
MARGARET V. RAGNI, M.D., ANDREW DEKKER, M.D., FREDERICK R. D E R U B E R T I S , M.D., CHARLES G. WATSON, M.D., M. LEON SKOLNICK, M.D., SUSAN D. GOOLD, M.D., MICHAEL W. FINIKIOTIS, M.D., SALIL DOSHI, M.D., AND DELYNNE J. MYERS, M.D.
Extrapulmonary Pneumocystis infection has been increasingly reported in patients with acquired immune deficiency syndrome (AIDS), in particular, recently in association with the increasing use of aerosolized pentamidine. This report describes the unusual presentation of extrapulmonary Pneumocystis infection as a thyroid neck mass and clinical hypothyroidism in a 37-year-old man with hemophilia and AIDS. This case differs from the previously reported single case of isolated thyroid pneumocystosis in the presence of a rapidly enlarging neck mass, lack of previous Pneumocystis, and prior prophylaxis with aerosolized pentamidine. The pathologic and electron microscopic description of the
peculiar flocculent necrotic thyroid material is contrasted with typical pulmonary alveolar findings in Pneumocystis pneumonia (PCP), the differential diagnoses of a rapidly expanding neck mass, and diagnostic difficulties of hypothyroidism in patients with AIDS are discussed. Finally, it is emphasized that use of aerosolized pentamidine, although successful for prevention of pulmonary PCP, may be insufficient to prevent extrapulmonary infection. (Key words: Pneumocystis carinii pneumonia |PCPJ; Acquired immune deficiency syndrome (AIDS); Extrapulmonary pneumocystosis; Thyroid mass) Am J Clin Pathol 199I;95: 489-493
Despite advances in treatment and prophylaxis, Pneumocystis carinii pneumonia (PCP) continues to be the most c o m m o n opportunistic infection reported in patients with acquired immune deficiency syndrome (AIDS), with more than 60% of patients with AIDS presenting with PCP and another 20% having PCP as a later diagnosis.1,2 Although PCP is regarded as a primary pulmonary pathogen, there have been increasing reports of extrapulmonary
Pneumocystis infection.3"5 These may relate, in part, to the recent introduction of aerosolized pentamidine, 6 which, with only minimal systemic absorption,7 promotes eradication of pulmonary Pneumocystis while allowing unchecked development of nonpulmonary Pneumocystis. Recently we cared for a patient with hemophilia and AIDS who presented with an acute diffuse goiter, hypothyroidism, and P. carinii of the thyroid.
REPORT OF A CASE From the Departments ofMedicine. Radiology, Surgery, and Pathology, University of Pittsburgh School ofMedicine, and the Hemophilia Center A 37-year-old man with severe hemophilia A (< 0.01 U/mL Factor of Western Pennsylvania, Pittsburgh, Pennsylvania. VIII:C) and AIDS presented in July 1989 with a painful right neck mass and transient dysarthria. There had been no trauma. Ultrasound revealed Received March 8, 1990; received revised manuscript and accepted the mass to be an enlarged right lobe of the thyroid, with echogenic areas for publication April 5, 1990. consistent with calcification and suggestive of hematoma. The left lobe Address reprint requests to Dr. Ragni: Hemophilia Center of Western appeared normal. Treatment with Factor VIII concentrate therapy rePennsylvania, 812 Fifth Avenue, Pittsburgh, Pennsylvania 15219.
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Pneumocystis carinii Infection Presenting as Necrotizing Thyroiditis and Hypothyroidism
