Iris Metastasis From a Bronchial Carcinoid Tumor Merlyn Rodrigues, MD, Jerry A. Shields,
MD
\s=b\ A 54-year-old man had a fleshy pink vascularized mass in the superonasal quadrant of the right iris. He had a history of an unchanging pulmonary nodule that was followed up for five years with routine chest roentgenograms. Fluorescein angiography demonstrated early filling of numerous fine blood vessels in the mass and diffuse late staining of the lesion. Results of a transcorneal radioactive phosphorus (32P) uptake test were positive. The clinical diagnosis was tapioca melanoma of the iris, with metastatic tumor as a second possibility. The tumor was excised by iridocyclectomy. Light microscopy revealed nests of tumor cells with oval hyperchromatic nuclei. Fontana stains for melanin were negative as were argentaffin and argyrophil stains. Electron microscopy demonstrated light and dark tumor cells containing numerous membrane-bound electrondense neurosecretory granules. The diagnosis was iris metastasis from a probable bronchial carcinoid. The patient is alive and well three years after excision of the iris mass.
probable bronchial carcinoid tumor, the diagnosis of which was confirmed by electron microscopy.1-2 REPORT OF A CASE A 54-year-old man who had no previous systemic or ocular complaints was noted by his family to have a pink iris lesion in the right eye. His medical history was normal except that he had had a lung lesion of possible neoplastic origin noted on a
routine chest roentgenogram five years earlier. Subsequently, yearly roentgenograms had revealed no change in the lesion. On examination in the Oncology Unit, Retina Service, Wills (Philadelphia) Eye Hospital, the patient had no complaints and routine physical examination was
Fig 1.—Prominent blood quadrant.
vessels
(arrow)
(Arch Ophthalmol 96:77-83, 1978) carcinoid tumors to the been eye are rare. There five cases of choroidal metastasis from bronchial carcinoid tumors. We report the first case of solitary iris metastasis from a
have Metastatic only previously reported
for publication April 13, 1977. From the Pathology Department and Oncology Unit, Retina Service, Wills Eye Hospital, Philadelphia. Dr Rodrigues is now with the Laboratory of Vision Research, NEI, Bethesda. Presented at the Pan-American Society of Ophthalmic Pathology, Santiago, Chile, March 18, 1977. Reprint requests to Wills Eye Hospital, 1601 Spring Garden St, Philadelphia, PA 19130 (Dr
Accepted
Shields).
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
are
normal. His uncorrected visual acuity was 6/15 with pinhole. The applanation pres¬ sure was 16 mm Hg in both eyes. Results of a complete ocular examination were normal except for an elevated, amelanotic, fleshy-pink mass occupying the entire superonasal quadrant of the right iris (Fig 1). The pupil was round without ectropion iridis. The lesion was in contact with the peripheral corneal endothelium, and gonioscopy demonstrated that it filled the anterior chamber angle in the supero¬ nasal quadrant (Fig 2). Transillumination revealed a normal pattern with no shadows in the ciliary body region. Fluorescein angiography demonstrated early filling of numerous fine blood vessels within the mass and diffuse late staining of the entire lesion. A radioactive phosphorus (32P) uptake test was performed by the noncut-
present
in
fleshy iris
mass
in
superonasal
Fig 2.—Gonioscopy angle.
demonstrates tumor
chamber
Fig 3.—Chest roentgenogram showing right anterior interspace.
involving
nodule
ting technique3 and revealed an uptake of 208% with the use of a unit that detects ocular tumors and of 232% with the use of a solid-state semiconductor detector.' The clinical diagnosis was "tapioca" melanoma of the iris OD.4 The differential diagnosis included metastatic tumor, sarcoid granuloma, and xanthogranuloma. Results of laboratory studies including
(arrows)
anterior
in third
Fig 4.—Tumor cells are arranged in nests (arrows) separated by (hematoxylin-eosin, original magnification 200).
CBC, urinalysis, fasting blood glucose, BUN, alkaline phosphatase, SCOT, and
lactic dehydrogenase were normal as was the ECG. Chest roentgenograms revealed a nodule (Fig 3) measuring 1.5 to 2.0 cm in the third anterior interspace on the right side, with an enlarged hilar shadow. The patient was examined by several ophthalmic consultants, all of whom fa¬ vored the diagnosis of tapioca melanoma of the iris and suggested that the tumor be excised by iridocyclectomy. Under general anesthesia, a limbal inci¬ sion was performed for 180° superonasally and the anterior chamber was entered. Radial iris incisions were made from the pupillary margin to the iris root on either side of the mass. By gently pulling the freed tumor centrally toward the pupil, it was noted that the lesion extended only to the anterior portion of the pars plicata and it was excised en bloc. There was slight vitreous loss, and a localized vitrectomy was performed. A small hyphema present in the immediate postoperative period had
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
fibrous strands
Fig 5.—Neoplastic cells are composed of oval hyperchromatic nuclei with prominent nucleoli and moderate amount of cyto¬ plasm (hematoxylin-eosin, original magni¬ x500).
fication
Fig 6.—Electron micrograph of light (L) and dark (D) tumor cells with prominent interdigitations ( 5,350).
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Fig 7.—Electron micrograph showing myriad electron-dense neurosecretory granules (arrows) prominent mitochondria (M) in cytoplasm of tumor cells (x 12,850). resolved by the first day. The patient was discharged on the fifth postoperative day with a pinhole visual acuity of 6/30. A 24hour urine specimen showed normal 5-hydroxy-indole acetic acid levels. The patient was referred to a thoracic surgeon for further evaluation of the chest
lesion, but he refused additional evaluation and treatment.
HISTOPATHOLOGICAL FINDINGS The gross specimen consisted of two pieces of tan-colored tissue, the larger measuring 8x5x3 mm and the smaller, 6x4x3 mm. A sample was removed for electron microscopy and was fixed in 2.5% buffered glutaralde-
hyde, dehydrated in ascending con¬ centrations of alcohol, and embedded in an epoxy resin. Thick sections were stained with toluidine blue and thin sections with uranyl acetate and lead citrate and they were examined with the electron microscope. The portion for light microscopy was fixed in 3.7% formaldehyde solu¬ tion and embedded in paraffin. The sections were stained with hematoxy¬ lin-eosin, PAS, Fontana-Masson, diazo argentaffin stain, and the Sevier Munger argyrophil stain. Microscopic examination revealed an iris tumor characterized by neo¬ plastic cells arranged in nests (Fig 4)
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
and
with numerous prominent blood ves¬ sels and scattered areas of hemor¬ rhage. The tumor cells displayed oval hyperchromatic nuclei with prominent nucleoli and a moderate amount of
eosinophilic cytoplasm (Fig 5). Special stains were negative for melanin, argentaffin and argyrophil granules, and for glycogen. At low magnification, electron mi¬ croscopy demonstrated prominent in¬ terdigitations between light and dark tumor cells (Fig 6) with surrounding basal lamellae. The dark cells con¬ tained closely packed microtubules and microfilaments with numerous electron-dense membrane-bound neu-
Fig 8.—Electron micrograph of clear tumor cell showing fewer neurosecretory gran¬ ules (arrows), lipid material (L), and mito¬ chondria. Nucleus is indicated by letter N. Adjacent dark tumor cell is indicated by asterisk (original magnification 16,250).
Fig 9.—Neurosecretory granules (arrows) varying size in tumor cells ( x 60,300).
of
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Fig 10.—Neurosecretory granules (G) are characterized by central electron-dense core adjacent small electron-lucent space surrounded by membrane (original magnifica¬ 68,500).
with tion
rosecretory granules (Fig 7). The clear or paler cells (Fig 8) had more loosely
lucent space. Occasional lipid material was also present (Fig 8).
The tumor cell nuclei were round to oval and contained coarsely clumped chromatin and small prominent nu¬ cleoli. The cytoplasm contained rough and smooth endoplasmic reticulum,
In a study of 227 patients with carcinomas metastatic to the eye and orbit, Ferry and Font'' noted that the breast was the most common primary site and the lung the next in frequen¬ cy. Although bronchogenic carcinomas have a propensity for early metasta¬ sis, often preceding clinical detection of the primary tumor, métastases from bronchial carcinoid neoplasms are usually delayed and the survival is greater than for bronchogenic carci¬
arranged organdíes, less abundant microfilaments, and microtubules.
mitochondria, well-developed golgi bodies, and myriad uniform mem¬ brane-bound electron-dense granules
that varied in size from 230 to 250 n m in diameter (Fig 9 and 10). They were characterized by a central electrondense core that was separated from an outer membrane by a narrow electron-
COMMENT
noma.5
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Carcinoid tumors originate from the Kultschitzky cells of the enterochromaffin system in the intestine and lung. They occur in all age groups from the first to the eighth decades and affect both sexes equally.6 Carcinoid tumors appear grossly as firm, yellowish or gray-white circum¬ scribed lesions. Microscopically, neoplástic cells are round or polygonal and are arranged in nests, strands, or cords that are separated by connective tissue. On fixation in formaldehyde, the cytoplasmic granules may reduce certain silver or chromic salts, demon¬ strating the argentaffin or chromaffin features. Other histochemical reac¬ tions used for the diagnosis of carci¬ noid tumors include the argyrophilic reaction, the reduction of ferric ferricyanide, and the azo-coupling reac¬ tion. However, these histochemical properties cannot be demonstrated in all carcinoid tumors and are rarely positive in pulmonary carcinoids.7 They may be negative in carcinoids of the appendix8 and colon." This is consistent with the negative argen¬ taffin stains in our case. Serotonin-containing tumors have been shown to exhibit golden yellow fluorescence in frozen sections fixed with formaldehyde.'" However, Gloor and associates" demonstrated that mastocytes in bronchial carcinoids exhibit autofluorescence by this meth¬ od as well as silver-reducing proper¬ ties, and should be differentiated from the true carcinoid tumor cells. Electron microscopy is useful in demonstrating the light and dark cells and the typical membrane-bound neu¬ rosecretory granules,12'115 as illus¬ trated in our case. Métastases to the anterior segment of the eye are much less common than métastases to the choroid,16 and an isolated iris metastasis, as in our patient, is even more unusual. The presenting ocular symptoms and signs in carcinoma metastatic to the ante¬ rior segment of the eye include decreased vision, presence of a mass,
redness, pain, iridocyclitis, glaucoma, and hyphema.1" In our case there was no glaucoma or epibulbar congestion, although these features were present in approximately 50% of the 26 patients reported by Ferry and Font.16
The latter also noted that the metastases involved the nasal or temporal meridian more frequently than the superior or inferior quadrant. In our case, the pinkish tumor was located superonasally and displayed consid¬ erable vascularity. Fluorescein angiography demon¬ strated early filling of numerous tumor blood vessels and diffuse late staining of the entire mass. These features are identical to what one sees with amelanotic iris melanomas, which are often highly vascularized. We routinely perform fluorescein an¬ giography on all suspicious growths of the iris although it may not always be of diagnostic value. In our case, it demonstrated the extensive vasculari¬ ty of the mass but was not of diag¬ nostic significance. In the present case, the elevated radioactive '-'P uptake test value was consistent with values observed in metastatic tumors as well as malignant melanoma.3 In three previous reports of bron¬ chial carcinoid with choroidal metas¬ tasis, li2·17 the age range of the patients was 12 to 29 years. Our patient was in his fifth decade before the iris tumor was noted. Electron microscopy of two previously reported cases of choroidal metastasis from bronchial carcinoid'2 tumors and an optic nerve metastasis from a mediastinal carcinoid'" re¬ vealed characteristics of neurosecre-
tory granules similar to those noted in our
patient.
The incidence of metastasis in bron¬ chial carcinoid tumors ranges from 10% to 15%.19 The regional lymph nodes are the most common site of metastasis, and less frequently the tumor metastasizes to skin, liver, and bone.2" Our patient did not manifest evidence of the carcinoid syndrome. However, very few carcinoid tumors are associated with systemic features of the syndrome.6 The five-year survival rate of carci¬ noid tumors ranges from 57% to 95%.21 Patients with métastases have sur¬ vived for five to 15 years. Microscop¬ ically, no distinction is possible be¬ tween the apparently benign carci¬ noid tumor, metastatic tumor, and neoplasms associated with the carci¬ noid syndrome." However, it is known that cylindromas metastasize three times as frequently as carcinoids. The histopathological differential diagnosis includes tapioca melanoma,4 nonchromaffin paraganglioma,22-23 and chemodectoma.24 Electron micros¬ copy of our case showed no evidence of immature or mature melanosomes in the cytoplasm of tumor cells, sugges¬ tive of a tapioca melanoma. Nonchro¬ maffin paraganglioma and chemodec¬ toma usually involve the orbit rather than the eye and can be differentiated from carcinoid tumors by histochem-
ical staining reactions and catecholamine fluorescence. The treatment of choice for carci¬ noid tumors in general is wide resec¬ tion of the primary lesion with exci¬ sion of regional lymph nodes and any accessible métastases. In our case, the patient refused excision of the pulmo¬ nary nodule and the nature of the tumor became evident by electron microscopy of the iris metastasis. Chemotherapy is usually required for patients with widespread métastases or with the carcinoid syndrome.2" Most carcinoid tumors seem to be radioresistant.2 The recommended treatment for metastatic tumors to the eye is irra¬ diation and chemotherapy. Perhaps an exception to this is the solitary metas¬ tasis from carcinoid tumors.2 In our case, the tumor showed fairly rapid growth and would probably have produced glaucoma and other compli¬ cations. Since carcinoid tumors are often radioresistant,2 local excision may be justified in such instances. Our patient is alive and well with no evidence of other metastasis three years after excision of the iris lesion. This study was supported in part by grants from the Pennsylvania Lions Eye Research Foundation, the Pennsylvania Odd Fellows Visual Research Foundation, and the Retina Research and Development Foundation, Phil¬
adelphia.
References 1. Fu Y, McWilliams NB, Stratford TP, et al: Bronchial carcinoid with choroidal metastasis in an adolescent. Cancer 33:707-715, 1974. 2. Bell RM, Bullock JD, Albert DM: Solitary choroidal metastasis from bronchial carcinoid. Br J Ophthalmol 59:155-163, 1975. 3. Shields JA, Carmichael PL, Leonard BC, et al: The radioactive phosphorus uptake test in the diagnosis of ocular tumors, in Croll MN, Brady LW, Carmichael PL, et al (eds): Nuclear Ophthalmology New York, John Wiley & Sons, Inc, 1976, pp 79-88. 4. Reese AB, Mund ML, Owamoto T: Tapioca melanoma of the iris: Part I. Clinical and light microscopy studies. Am J Ophthalmol 74:840-861, 1972. 5. Ferry AP, Font RL: Carcinoma metastatic to the eye and orbit: I. A clinicopathologic study of 227 cases. Arch Ophthalmol 92:276-286, 1974. 6. Simpson AJ: The carcinoid tumor, syndrome and spectrum. NC Med J 30:399-414, 1970. 7. Weiss L, Ingram M: Adenomatoid bronchial tumors: A consideration of the carcinoid tumors and the salivary tumors of the bronchial tree. Cancer 14:161-178, 1961. 8. Rosai J, Rodriguez HA: Application of electron microscopy to the differential diagnosis of tumors. Am J Clin Pathol 50:555-562, 1968.
9. Hernandez
FJ, Fernandez BB: Mucus-
secreting colonic carcinoid tumors: Light electron microscopic study of three cases. Colon Rectum 17:387-396, 1974. 10. Barter
and Dis
R, Pearse AGE: Detection of
5-hydroxytryptamine in
mammalian enterochromaffin cells. Nature 172:810-816, 1953. 11. Gloor E, Campiche M, Bauman RP: Mastocytes, autofluorescent and silver reducing elements in bronchial carcinoids. Virchows Arch [Pathol Anat] 357:19-28, 1972. 12. Bensch KG, Gordon GB, Miller LR: Electron microscopic and biochemical studies on the bronchial carcinoid tumor. Cancer 18:592-602, 1965. 13. Patchefsky AS, Gordon G, Harrer WV, et al: Carcinoid tumor of the pancreas: Ultrastructural observations of a lymph node metastasis and comparison with bronchial carcinoid. Cancer 33:1349-1354, 1974. 14. Weichert RF, Rothe LM, Harkin JC: Carcinoid-islet cell tumor of the duodenum and associated multiple carcinoid tumors of the ileum. Cancer 27:910-918, 1971. 15. Soga J, Tazawa K, Ifo H: Ultrastructural demonstration of specific secretory granules of Mastomys gastric carcinoids. Acta Med Biol 17:119-124, 1969.
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
16.
Ferry AP,
Font RL: Carcinoma metastatic
clinicopathological study of 26 patients with carcinoma metastatic to the anterior segment of the eye. Arch Ophthalto the eye and orbit: II. A
mol 93:472-482, 1975. 17. Rosenbluth J, Laval J, Weil JV: Metastasis of bronchial adenoma to the eye. Arch Ophthalmol 63:47-50, 1960. 18. Fishman ML, Rosenthal S: Optic nerve metastasis from a mediastinal carcinoid tumor. Br J Ophthalmol 60:583-588, 1976. 19. Toker C, Fry WA, Head L, et al: Bronchial adenoma (carcinoid type). Cancer 19:1943-1948, 1966. 20. Hajdu SI, Winawer SJ, Myers WPL: Carcinoid tumors: A study of 204 cases. Am J Clin Pathol 61:521-528, 1974. 21. O'Grady WP, McDivitt RW, Holman GW, et al: Bronchial adenoma. Arch Surg 101:558-561, 1970. 22. Deutsch AR, Duckworth JK: Nonchromaffin paraganglioma of the orbit. Am J Ophthalmol 68:659-663, 1969. 23. Litricin O: Orbital nonchromaffin paraganglioma. Ann Oculist 203:585-592, 1970. 24. Zawirska B, Drozdowska S: Recurrent chemodectoma of the orbit. Ann Oculist 203:361\x=req-\ 370, 1970.
MD
\s=b\ A 54-year-old man had a fleshy pink vascularized mass in the superonasal quadrant of the right iris. He had a history of an unchanging pulmonary nodule that was followed up for five years with routine chest roentgenograms. Fluorescein angiography demonstrated early filling of numerous fine blood vessels in the mass and diffuse late staining of the lesion. Results of a transcorneal radioactive phosphorus (32P) uptake test were positive. The clinical diagnosis was tapioca melanoma of the iris, with metastatic tumor as a second possibility. The tumor was excised by iridocyclectomy. Light microscopy revealed nests of tumor cells with oval hyperchromatic nuclei. Fontana stains for melanin were negative as were argentaffin and argyrophil stains. Electron microscopy demonstrated light and dark tumor cells containing numerous membrane-bound electrondense neurosecretory granules. The diagnosis was iris metastasis from a probable bronchial carcinoid. The patient is alive and well three years after excision of the iris mass.
probable bronchial carcinoid tumor, the diagnosis of which was confirmed by electron microscopy.1-2 REPORT OF A CASE A 54-year-old man who had no previous systemic or ocular complaints was noted by his family to have a pink iris lesion in the right eye. His medical history was normal except that he had had a lung lesion of possible neoplastic origin noted on a
routine chest roentgenogram five years earlier. Subsequently, yearly roentgenograms had revealed no change in the lesion. On examination in the Oncology Unit, Retina Service, Wills (Philadelphia) Eye Hospital, the patient had no complaints and routine physical examination was
Fig 1.—Prominent blood quadrant.
vessels
(arrow)
(Arch Ophthalmol 96:77-83, 1978) carcinoid tumors to the been eye are rare. There five cases of choroidal metastasis from bronchial carcinoid tumors. We report the first case of solitary iris metastasis from a
have Metastatic only previously reported
for publication April 13, 1977. From the Pathology Department and Oncology Unit, Retina Service, Wills Eye Hospital, Philadelphia. Dr Rodrigues is now with the Laboratory of Vision Research, NEI, Bethesda. Presented at the Pan-American Society of Ophthalmic Pathology, Santiago, Chile, March 18, 1977. Reprint requests to Wills Eye Hospital, 1601 Spring Garden St, Philadelphia, PA 19130 (Dr
Accepted
Shields).
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
are
normal. His uncorrected visual acuity was 6/15 with pinhole. The applanation pres¬ sure was 16 mm Hg in both eyes. Results of a complete ocular examination were normal except for an elevated, amelanotic, fleshy-pink mass occupying the entire superonasal quadrant of the right iris (Fig 1). The pupil was round without ectropion iridis. The lesion was in contact with the peripheral corneal endothelium, and gonioscopy demonstrated that it filled the anterior chamber angle in the supero¬ nasal quadrant (Fig 2). Transillumination revealed a normal pattern with no shadows in the ciliary body region. Fluorescein angiography demonstrated early filling of numerous fine blood vessels within the mass and diffuse late staining of the entire lesion. A radioactive phosphorus (32P) uptake test was performed by the noncut-
present
in
fleshy iris
mass
in
superonasal
Fig 2.—Gonioscopy angle.
demonstrates tumor
chamber
Fig 3.—Chest roentgenogram showing right anterior interspace.
involving
nodule
ting technique3 and revealed an uptake of 208% with the use of a unit that detects ocular tumors and of 232% with the use of a solid-state semiconductor detector.' The clinical diagnosis was "tapioca" melanoma of the iris OD.4 The differential diagnosis included metastatic tumor, sarcoid granuloma, and xanthogranuloma. Results of laboratory studies including
(arrows)
anterior
in third
Fig 4.—Tumor cells are arranged in nests (arrows) separated by (hematoxylin-eosin, original magnification 200).
CBC, urinalysis, fasting blood glucose, BUN, alkaline phosphatase, SCOT, and
lactic dehydrogenase were normal as was the ECG. Chest roentgenograms revealed a nodule (Fig 3) measuring 1.5 to 2.0 cm in the third anterior interspace on the right side, with an enlarged hilar shadow. The patient was examined by several ophthalmic consultants, all of whom fa¬ vored the diagnosis of tapioca melanoma of the iris and suggested that the tumor be excised by iridocyclectomy. Under general anesthesia, a limbal inci¬ sion was performed for 180° superonasally and the anterior chamber was entered. Radial iris incisions were made from the pupillary margin to the iris root on either side of the mass. By gently pulling the freed tumor centrally toward the pupil, it was noted that the lesion extended only to the anterior portion of the pars plicata and it was excised en bloc. There was slight vitreous loss, and a localized vitrectomy was performed. A small hyphema present in the immediate postoperative period had
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
fibrous strands
Fig 5.—Neoplastic cells are composed of oval hyperchromatic nuclei with prominent nucleoli and moderate amount of cyto¬ plasm (hematoxylin-eosin, original magni¬ x500).
fication
Fig 6.—Electron micrograph of light (L) and dark (D) tumor cells with prominent interdigitations ( 5,350).
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Fig 7.—Electron micrograph showing myriad electron-dense neurosecretory granules (arrows) prominent mitochondria (M) in cytoplasm of tumor cells (x 12,850). resolved by the first day. The patient was discharged on the fifth postoperative day with a pinhole visual acuity of 6/30. A 24hour urine specimen showed normal 5-hydroxy-indole acetic acid levels. The patient was referred to a thoracic surgeon for further evaluation of the chest
lesion, but he refused additional evaluation and treatment.
HISTOPATHOLOGICAL FINDINGS The gross specimen consisted of two pieces of tan-colored tissue, the larger measuring 8x5x3 mm and the smaller, 6x4x3 mm. A sample was removed for electron microscopy and was fixed in 2.5% buffered glutaralde-
hyde, dehydrated in ascending con¬ centrations of alcohol, and embedded in an epoxy resin. Thick sections were stained with toluidine blue and thin sections with uranyl acetate and lead citrate and they were examined with the electron microscope. The portion for light microscopy was fixed in 3.7% formaldehyde solu¬ tion and embedded in paraffin. The sections were stained with hematoxy¬ lin-eosin, PAS, Fontana-Masson, diazo argentaffin stain, and the Sevier Munger argyrophil stain. Microscopic examination revealed an iris tumor characterized by neo¬ plastic cells arranged in nests (Fig 4)
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
and
with numerous prominent blood ves¬ sels and scattered areas of hemor¬ rhage. The tumor cells displayed oval hyperchromatic nuclei with prominent nucleoli and a moderate amount of
eosinophilic cytoplasm (Fig 5). Special stains were negative for melanin, argentaffin and argyrophil granules, and for glycogen. At low magnification, electron mi¬ croscopy demonstrated prominent in¬ terdigitations between light and dark tumor cells (Fig 6) with surrounding basal lamellae. The dark cells con¬ tained closely packed microtubules and microfilaments with numerous electron-dense membrane-bound neu-
Fig 8.—Electron micrograph of clear tumor cell showing fewer neurosecretory gran¬ ules (arrows), lipid material (L), and mito¬ chondria. Nucleus is indicated by letter N. Adjacent dark tumor cell is indicated by asterisk (original magnification 16,250).
Fig 9.—Neurosecretory granules (arrows) varying size in tumor cells ( x 60,300).
of
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Fig 10.—Neurosecretory granules (G) are characterized by central electron-dense core adjacent small electron-lucent space surrounded by membrane (original magnifica¬ 68,500).
with tion
rosecretory granules (Fig 7). The clear or paler cells (Fig 8) had more loosely
lucent space. Occasional lipid material was also present (Fig 8).
The tumor cell nuclei were round to oval and contained coarsely clumped chromatin and small prominent nu¬ cleoli. The cytoplasm contained rough and smooth endoplasmic reticulum,
In a study of 227 patients with carcinomas metastatic to the eye and orbit, Ferry and Font'' noted that the breast was the most common primary site and the lung the next in frequen¬ cy. Although bronchogenic carcinomas have a propensity for early metasta¬ sis, often preceding clinical detection of the primary tumor, métastases from bronchial carcinoid neoplasms are usually delayed and the survival is greater than for bronchogenic carci¬
arranged organdíes, less abundant microfilaments, and microtubules.
mitochondria, well-developed golgi bodies, and myriad uniform mem¬ brane-bound electron-dense granules
that varied in size from 230 to 250 n m in diameter (Fig 9 and 10). They were characterized by a central electrondense core that was separated from an outer membrane by a narrow electron-
COMMENT
noma.5
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/02/2015
Carcinoid tumors originate from the Kultschitzky cells of the enterochromaffin system in the intestine and lung. They occur in all age groups from the first to the eighth decades and affect both sexes equally.6 Carcinoid tumors appear grossly as firm, yellowish or gray-white circum¬ scribed lesions. Microscopically, neoplástic cells are round or polygonal and are arranged in nests, strands, or cords that are separated by connective tissue. On fixation in formaldehyde, the cytoplasmic granules may reduce certain silver or chromic salts, demon¬ strating the argentaffin or chromaffin features. Other histochemical reac¬ tions used for the diagnosis of carci¬ noid tumors include the argyrophilic reaction, the reduction of ferric ferricyanide, and the azo-coupling reac¬ tion. However, these histochemical properties cannot be demonstrated in all carcinoid tumors and are rarely positive in pulmonary carcinoids.7 They may be negative in carcinoids of the appendix8 and colon." This is consistent with the negative argen¬ taffin stains in our case. Serotonin-containing tumors have been shown to exhibit golden yellow fluorescence in frozen sections fixed with formaldehyde.'" However, Gloor and associates" demonstrated that mastocytes in bronchial carcinoids exhibit autofluorescence by this meth¬ od as well as silver-reducing proper¬ ties, and should be differentiated from the true carcinoid tumor cells. Electron microscopy is useful in demonstrating the light and dark cells and the typical membrane-bound neu¬ rosecretory granules,12'115 as illus¬ trated in our case. Métastases to the anterior segment of the eye are much less common than métastases to the choroid,16 and an isolated iris metastasis, as in our patient, is even more unusual. The presenting ocular symptoms and signs in carcinoma metastatic to the ante¬ rior segment of the eye include decreased vision, presence of a mass,
redness, pain, iridocyclitis, glaucoma, and hyphema.1" In our case there was no glaucoma or epibulbar congestion, although these features were present in approximately 50% of the 26 patients reported by Ferry and Font.16
The latter also noted that the metastases involved the nasal or temporal meridian more frequently than the superior or inferior quadrant. In our case, the pinkish tumor was located superonasally and displayed consid¬ erable vascularity. Fluorescein angiography demon¬ strated early filling of numerous tumor blood vessels and diffuse late staining of the entire mass. These features are identical to what one sees with amelanotic iris melanomas, which are often highly vascularized. We routinely perform fluorescein an¬ giography on all suspicious growths of the iris although it may not always be of diagnostic value. In our case, it demonstrated the extensive vasculari¬ ty of the mass but was not of diag¬ nostic significance. In the present case, the elevated radioactive '-'P uptake test value was consistent with values observed in metastatic tumors as well as malignant melanoma.3 In three previous reports of bron¬ chial carcinoid with choroidal metas¬ tasis, li2·17 the age range of the patients was 12 to 29 years. Our patient was in his fifth decade before the iris tumor was noted. Electron microscopy of two previously reported cases of choroidal metastasis from bronchial carcinoid'2 tumors and an optic nerve metastasis from a mediastinal carcinoid'" re¬ vealed characteristics of neurosecre-
tory granules similar to those noted in our
patient.
The incidence of metastasis in bron¬ chial carcinoid tumors ranges from 10% to 15%.19 The regional lymph nodes are the most common site of metastasis, and less frequently the tumor metastasizes to skin, liver, and bone.2" Our patient did not manifest evidence of the carcinoid syndrome. However, very few carcinoid tumors are associated with systemic features of the syndrome.6 The five-year survival rate of carci¬ noid tumors ranges from 57% to 95%.21 Patients with métastases have sur¬ vived for five to 15 years. Microscop¬ ically, no distinction is possible be¬ tween the apparently benign carci¬ noid tumor, metastatic tumor, and neoplasms associated with the carci¬ noid syndrome." However, it is known that cylindromas metastasize three times as frequently as carcinoids. The histopathological differential diagnosis includes tapioca melanoma,4 nonchromaffin paraganglioma,22-23 and chemodectoma.24 Electron micros¬ copy of our case showed no evidence of immature or mature melanosomes in the cytoplasm of tumor cells, sugges¬ tive of a tapioca melanoma. Nonchro¬ maffin paraganglioma and chemodec¬ toma usually involve the orbit rather than the eye and can be differentiated from carcinoid tumors by histochem-
ical staining reactions and catecholamine fluorescence. The treatment of choice for carci¬ noid tumors in general is wide resec¬ tion of the primary lesion with exci¬ sion of regional lymph nodes and any accessible métastases. In our case, the patient refused excision of the pulmo¬ nary nodule and the nature of the tumor became evident by electron microscopy of the iris metastasis. Chemotherapy is usually required for patients with widespread métastases or with the carcinoid syndrome.2" Most carcinoid tumors seem to be radioresistant.2 The recommended treatment for metastatic tumors to the eye is irra¬ diation and chemotherapy. Perhaps an exception to this is the solitary metas¬ tasis from carcinoid tumors.2 In our case, the tumor showed fairly rapid growth and would probably have produced glaucoma and other compli¬ cations. Since carcinoid tumors are often radioresistant,2 local excision may be justified in such instances. Our patient is alive and well with no evidence of other metastasis three years after excision of the iris lesion. This study was supported in part by grants from the Pennsylvania Lions Eye Research Foundation, the Pennsylvania Odd Fellows Visual Research Foundation, and the Retina Research and Development Foundation, Phil¬
adelphia.
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