t~ayo pathology alumni ~i.a. · produce a serious infarct, it might be wise to wrap the lesion in a...

8
PATHOLOGY ALUMNI SUDE SEMINAR NOV EMBER 22, 1980 Di scussion: Meis sne r, l.B. Woolne r, £nzinger, and E.H . Soule CASE 1 : CASE 2: . CASE 3: CASE 4: CASE 5: A man, ag e 19, noticed an il l -defined s11el1 i ng of h is rig ht neck for five months. At this time a lymph node was biopsied and reported as nodular hyperplasia. The swellin9 slowly increased over the next months . A surgical explo rati on revealed a lar9e soft tan colored invasive tumor in the right paraspinal muscle s. T he re was bone i n vo 1 vemen t. A man, age 70, had noticed an asymptomatic mass in his axilla for one year. Four mon ths a9o it began to enlarge and he de vel oped clinical evi dence of brachia l plexus involvement. Du ring th is period he had tempe rature elevation up to 102 degrees Fahrenheit. His 14.B.C. was 8,400 with 13.5% eosinophils. A 6 x 5 x 4 em invasive tumor was excised . A man, age 63, had experienced episodes of pain and of his right foot for 15 years. A diagnosis of gout had been but not established by his home physician. Hhen examined at the Clinic there was a firm mass on t he lateral aspect of his foot. An through the mi d- leg was done . A man, age 53, was found to have a mass on his right shoulder when he presented himself for a routine examinati on. The le sion was asymptoma ti c, has been present for 3-4 years but ha d enlarged during the past three month s. A circumscribed tumor 5 x 5 x 4 em exci sed from the subcutaneous tissue. A woman, age 51, was s een because of an enlarging mass deep in the left buttock. In 1969 a chor doma had been excised from her sacrum. The chordoma recurred in 1971 and it treated by surgical excision and radiation (5250 rads). In June of 1975 the patient was seen at the Mayo Cli nic because of a 1 a rge recurrence of the sacra 1 mass and pul monary nodules. The patient was given chemotherapy (vincristine, Cytoxan, dactinomy cin, Cis-Platinum). By January 1976 there comp lete remission of the sacral and pulmonary masses. In October of 1979 a mass in the left buttock was found and exc ised. The slides are froM this tumor.

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t~AYO PATHOLOGY ALUMNI

SUDE SEMINAR

NOV EMBER 22, 1980

Di scussion: ~I.A. Meissner, l.B. Woolner , F.~l. £nzinger, and E.H . Soule

CASE 1 :

CASE 2:

. CASE 3:

CASE 4:

CASE 5:

A man, age 19, noticed an il l -defined s11el1 i ng of his right neck for five months. At this time a lymph node was biopsied and reported as nodular hyperplasia. The swellin9 slowly increased over the next tl~o months . A surgical exploration revealed a lar9e soft tan colored invasive tumor in the right paraspinal muscles . There was bone i nvo 1 vement.

A man, age 70, had noticed an asymptomatic mass in his ri~ht axilla for one year. Four months a9o it began to enlarge and he devel oped clinical evidence of brachia l plexus involvement. During th i s period he had temperature elevation up to 102 degrees Fahrenheit. His 14.B.C. was 8,400 with 13.5% eosinophils. A 6 x 5 x 4 em invasive tumor was excised .

A man, age 63, had experienced episodes of pain and S~1ellin9 of his right foot for 15 years. A diagnosis of gout had been suspecte~ but not established by his home physician. Hhen examined at the ~~ayo Clinic there was a firm mass on t he lateral aspect of his foot. An a~putation through the mi d- leg was done .

A man, age 53, was found to have a mass on his right shoulder when he presented himself for a routine examination. The lesion was asymptomatic, has been present for 3-4 years but ha d enlarged during the past three months. A circumscribed tumor 5 x 5 x 4 em ~1as exci sed from the subcutaneous tissue.

A woman, age 51, was seen because of an enlarging mass deep in the left buttock. In 1969 a chordoma had been excised from her sacrum. The chordoma recurred in 1971 and it ~1as treated by surgical excision and radiation (5250 rads). In June of 1975 the patient was seen at the Mayo Cli nic because of a 1 a rge recurrence of the sacra 1 mass and t1~o pulmonary nodules. The patient was given chemotherapy (vincristine , Cytoxan, dactinomycin, Cis-Platinum). By January 1976 there 1~as complete remission of the sacral and pulmonary masses. In October of 1979 a mass in the left buttock was found and exc ised. The slides are froM this tumor.

CASE 6:

CASE 7:

CASE 8:

(~~>)

CASE 8: (B)

CASE 9:

CASE 10:

This 66-year-old ~10man noted a sudden throbbin9 pain in the anterior neck associated with a f eeling of obstruction in her throat. Her physician noted a mass in the left lobe of the thyroid. R.i,IR v1as reported as +2 and the P.B.I. 5 ug%. At the time of thyroi~ suroery, a 2 em circumscri bed nodule 1~as noted in the 1 eft 1 obe, represented by this section.

This 54-year-old asymptomatic .v10man durin(l duri n(l a routine examinati on was noted to have an enlarged thyroid gland and a firm noclul e in the left lobe, 2 em in diameter. Secti ons are from the nodule.

Mal e, 55, developed asymptomatic l ump in right mid neck lY, to 2 year s prior to admission. The mass ~?rew very slowly durino this perioci of time . Two 1·1eeks prior to admission, ri f!ht cervical lymph node was removed and the patient referred to the ~1ayo Clinic ~lith a rlia~nosis of metastatic carcinoma. There were no symptoms referabl e to chest or urinary tract. Admission chest x-ray: Pathologic process in right base, probably bronchiectasis . Examination: Mass in right neck 1·1hich does not move with swallowi n9. Thyroid primary versus metastatic cancer to neck. Surgery: Total right thyroid lobectomy with removal of isthmus . Sections are of right thyroid mass.

~1a 1 e, 70, came to the Mayo Clinic in ()ctober, 19.54, because of a l ump in the 1 eft side of the neck said to have been present for ~0 year s. Patient other1~i se asymptomatic. Surgery: Tota 1 r i 9ht thyroid 1 obectorny 1qith remova 1 of isthmus. Sections are of left thyroid mass.

Female, age 69, admitted on April 3, 1957, v1ith l ong history of ren111 calculi, mu l tiple fractures, tumor of ulna and mass in neck. Prior surgery: 1936 - Right total lobect omy of thyroi d; 1954 - Resection proximal thi·rd of ulna. Physical examination: Large nodular mass, left neck, extendinp beneath sternum. Tumorous enlargement of ri~ht lov1er ribs. Laboratory data: Serum calcium, 12.G mgms; phosphorus, 3 . ~ mprns per lOOcc serum; alkaline phosphorus, 2~7 units. Surgery: February 25, 1957: subtotal resection of the l eft lobe of the thyroid (right lobe resected prior). Hu~h cystic mass on the left displacing trachea markedly to the ri9ht extending beneath sternum. r·,lass resected ~1eighed 132 grams. Sections are from mass adjacent to thyroid.

Female , age 24, presented with asymptomatic nodule in thyroirl oland. Sections are from thyroid nodule.

DIAGNOSES

CASE 1: Extra-osseous Ewing's sarcoma.

CASE 2: Angioblastic lymphoid hyper plasia ~lith bl ood eosinophilia (Kimura's disease).

CASE 3: Synovial sarcoma.

CASE 4: Pleomorphic l ipoma.

CASE 5: Malignant fibrous histiocytoma, inflammatory variant .

CASE 6: Nedullary carcinoma ,,•ith ca1:cinoid syndrome. Reported by Hoertel , et al, New England Journal of Medicine, 273:244, 1965 .

CASE 7 : ?Hedullary carcinoma vs. spindled trabecular adenoma . Patient is 13 years postoperative '"ith no recurrence.

CASE 8: Clear cell tollicular carcinoma: primary in thyroid. (a)

CASE 8: Hetastatic renal cell carcinoma (hypernephroma) . (b)

CASE 9: P.rimary ~<aterclear hyperplasia of parat hyroid glands.

CASElO : Chemodectoma (cellular with mitoses) in thyroid gland . 4 years later.

Patient is '~ell

'

THE NEW E~GL-\.l'ID JOUR.I.~AL OF ~1 EDICIXE_ Jul>· 29, 1965 .

wo!!ld not be devastati."lg; this proved to be correct. .\!though the "blowout" on the artery suggested th a : the subacute infection remained confined to a stnaller area of the wall inspection of these aneu­rysms show~d that the necks had a broad origin from at least half the circumference. A clip or ligature would surely have occluded the vesseL

applied only to aneurysms on major vessels and should be based on the improbability of safe sur­gical treatment <1;t an earlier stage. In cases in which ligation or .excision is not possible, or would produce a serious infarct, it might be wise to wrap the lesion in a plastic jacket and relr on :1nti. biotics to destroy the infe.ction within.

St:..-~L\fARY .\."'<"D CoNCLUSIONS

The urgency of craniotomy depends on the site of the aneurysm and whether a significant clot is pres­ent In 3 cases a large intracerebral clot prompted i:nmedia te operation. These p atients fared poorly; Rupture of a cerebra l aneurysm caused by mycotic Case 2 died, and Cases I and 3 were left with pet=-- organisms i:; a rare cause of spontaneous intracranial manent severe deficits. It is unfortunate that the bleeding. Of 191 cases 5 (2.6 per cent) were oi in­r.ature o£ the first aneurysm in Case 3 was notl fectious origin ( 1 patient had 2 such aneurysms) . recognized, for treatme~ght have prevented the ' These cerebral aneurysms should be suspected i[

se,:ere hemorrhage fro e second three months· there is an ob\-ious infec tion, murmur, splenomegaly, later. • petechiae, microscopical hematuria, fe\·er o:- elc:v:ued

In the absence of significant clot or repeated sedimentation rate, an aneurysm in a peculiar si:e hemorrhages the location of the aneurysm will de- or a second aneurysm. termine the priority of medical or surgical treat- -_ Each aneurysm was treated surgically. T wo pa­ment. The more peripheral aneurysms should be ex- tients are well; 1 is dead, and 2 h::t\·e serious neuro­cised or obliterated promptly since the ensuing logic deficit. :'\one have clinically significant he:lrt neurologic deficit is likely to be negligible. If the disease. aneurysm arises from a major vessel a delay of oper- Peripheral aneurysms should be excised or lig:ued ation must be considered. :\Iassive appropriate anti- immediately. Aneurysms im·oh·ing major ves;e!~

biotic therapy should destroy the organism and allow · should probably be treated with antibiotics initi:t:iy wme reparative fibrosis to take place in the wall of unless a significant clot is present. Although tlill the aneUiysm and parent artery. A dip or ligature delay carries the J;sk of recurrent bleeding, the re...<o­

can then more safely be applied, and the unfortu- lution of the arterial infection should ma!.;e the nate consequences of an operation on a fragile, an eurysm less fragile for surgical treatment. acutely inflamed aneurysm, as in Case 2, thus avoid-ed. Such a delay is undoubtedly dangerous because of the possibility of repeated bleeding. In addition the aneurysm may enlarge, as shown angiographical­

REFERE!'OCES

I. O sler, W. Guluonian lectures on m;ilignu t endoc;,rtliis. L:-.nt I :415-418, 459-46-1 a nd 503·508, L885.

ly in Case 4 during the four-·week period of anti- z. biotic treatment. T he decision for delay should be 3.

McDonald, C. .-\. , nnd Korb, ~(. Introer:tnial >••euqsclS. -~ttl. N eurol. & Psychittt. 42:298-328, 1939. Barker, W. F. ~)·corie :.neurysms. A nn. S urz . 1 39 :~-89. 1~-

"MALIGNAl'J'T CARCINOID SYNDROME" ASSOCIATED WITH NONCARCINOID WMORS*

CHARLES G. MOERTEL, M.D.,t OLIVER H. BEAHRS, M.D.,:j: L E \VIS B. \VOOLNER, }.f.D.,§ ANO

G ERTRUDE M. TYeE, PH.D.1f

ROCHESTER, l\ll NNESOTA

DURING the past decade the "malignant carci-noid syndrome" has been a fa ,·ored subject in

the medical literatu re because of the dramatic na­ture of its acute and chronic clinical manifestations and of its as yet unresolved challenges to the physiol-

• Frorn the -ections of ~fedicine, Su<3cry. Su rgie:.l Pathology and Bio-ch<:!>:itry, ~fa~o Clinic a nd :\!;,yo Found3tion.

+)[ember, Sec-:ion of ~lcdicin~, ).f;.yo Clinic and 1\fayo Foundation. ! :'-!e mbe r, Section of Surgery. :\layo Clinic :1nd llh~·o Found:>tion. i~Je:n?er, See tiun of Surgie3.1 P:1thology, ~fayo Clinic 31\d ~byo

f ound:tt:on. • :.!ember, Section d Biochemi•tcy, M:1yo Clini.: and 1>-hyo Foundation.

ogist and thera pist. Still more fascinating are recent reports that the syndrome has been produced b~· noncarcinoid t umors. T o date, 7 such unusl:::d c:1>t!S

have been adequately documen~ed and recordectt·r: in 3, the primary carcinoma had .its origin in the! pancreas1•3 ; in 3, the primary lesion was an oat-cc:U carcinoma of the lung; and in 1, it was a highly anaplastic carcinoma with the site of origin unde­teJminecV T he pertirient data in these case5 ~ summ.arized in T able I. This report adds an eighili case to this elite circle - a "malignant carcinoid

273 Xo. 5 :-L-\LIGX.-'L'\T CARCTXOID S't-:-.'"DRO:-H: - ~10ERTEL ET AL. 245

,_!!!LT. J. Summar)' of R tported Cases of "Malignan: Ccrc:Z·:'lid S>·ndromc" Cc-existent u:ith Jo:oncarcinoid J.falignant Neo­pla!m.!.

Mullen & H anson' Carcinorn:~. in p an­creas

Carcinoma in pan· creas

Islet-cell carcinoma in pancreas

Oat-<ell Pj carci­noma m ung

~ & Azzopardi' Oat-cell carcinoma in lung

•tnlock et aJ.• Oat-cell carcinolDJ\ in lung

p et al. 1 Anaplastic carci-noma of u n­known origin

~ydroxyindoleaatic acid. :11: i\.i.rdro:cyt:r)-pto.miue. fbl-droJ<Ttryptophan.

CuxtC\L ~1.-..."""tt"l.~· TAT!O~S

.3-HL~-\.•

rng./dcy .

F lushing; asthnt:l. ustrongh· positive.,

Flushing 460~90

Flushing; diarrhea; asthma.

53-88

Flu!hing : diarrhea; "Greater (?) asthma. than nor-

mal" F!usbing; diarrhea. 55#..1

( ?) F!uslllng; diar-r hea.

130-230

Flushiog 113-160

drome" coexistent with and presumably produced primary solid thyroid carcinoma " ; th metas-

CASE REPoRT

! 66-year-old woman was first admitred to the Mayo ~k on April 13, 1962, because of a mass in the neck that had noted accidentally 2 rnomhs pre,·iously. She had no s.ignifi~t symptoms, a11d physical examination re­

,ttJ only a solitary, firm, 2-cm. nodule in the left lobe of thrroid gland. Results of basic laboratory studies a nd

~mlent of thyroid fu nction were with in nonnal Umits. April 20 a total lobectomy on the left and subtotal ~omy on the right, ,,-jth remo,·al of the thyroid istht:lu.s, 1 perfonned. At operation the left inferior parathyroid d ,,·as noted to be enlarged and " ·as also excised, as

• the tracheoesophageal lymph nodes. Adenopathy was ooted atong the jugular vein. Pathological examination ~ed a circumscribed, infiluati,·e carcinoma, 2 em. in ptter, in the left lobe of the thyToid gland. I n acdition, ::1 was a single H iirthle-cell adenoma, 1.5 em. in diam­r, within the loue. The right lobe sho,,·ed normal thyroid ~ch:-ma, "ith slight focal fibrosis. ptologically, the carcinon1a was moderately acri,·e ( Grade ):cording to Broders' s classification) and had a solid pat­

(fig. 1 a ) . Some · central hyaline fibrosis ,,·as present. .ough solid ( nonglandular), the tumor appeared some­<1 more active than the subtype of thyroid carcinoma tha t l:tsently referred to as "solid (medullary) carcinoma with

tid stroma." :Mitotic acti\; t). seemed somewhat less that seen in the anaplastic fonn of thyroid cancer. ossl)•, the parathyroid adenoma was 8 mm. in diameter •'cighed 350 mg. Microscopically, it consisted of mixed

!II. o>.:yphil and transitional water-clear cells. · ~use of the parathyroid adenoma the serum calcium rletermined at the time of operacion and " ·as found to 13.3 mg. per 100 ml. (nonnal, 8.9 to JO.l mg. ) . Twent)·­hours after operation the value "·as 8. 7 tng.; at 6 days,

8.9 mg., and on the lith postoperative day, it had to 9.6 mg. Although data were incomplete, it was 25·

that this patient had had prima ry hyperparath~·roidism. Februarr, 1963, she noted enlarged lymph nodes in the

tde of the neck. She rerumed to the Clinic on :\Ia'· 3. a radical neck d issection was performed . Pathological nation shO\,·ed metastatic, Grade 3, solid carcinoma · g multiple lymph nodes of the lfliddle· and the lower jugular regions. The histologic architecture was iden­•ith tl1at of the tumor in the corresponding lobe pre-

'1l resected l fig. lb) .

t:';;.rs..a .... q,·, '£.~"':::"-r..:.-riOX Tt:>-lOR Coxn:---r

5·=+ j.HTr! HlST .. ·UrT!'ol"'E 5-Jtr+ 5·HTT':

mg./dey n-:;z./day mg./day microgn ./ miCTotm./ g m. gm.

0.330-0.49.5 4

:"onnal ::-.-onn.al None

20

12-21 12·1i 0.022-1 .260 < 0.04 <0.05

4000.0

The patient remained asymptomatic during 1963 and early 196-4. She returned again on .-\ugust 25, 1964, ,,·hen she stated that ior 6 months she had had recurrent attacks of intense flushing invoh-ing the face and chest. The attacks occasionally c=e on after the ingestion of a large meal but were in,-ar'.ably precipita ted by the use of alcohol. YeT)~ small quantities of alcohol were required to precipitate an attack. and she became flushed after taking a sip of her nu.s3and·s beer or a single teaspoonful of eliw oi terpin hydrate and codeine, " ·hich she took for a cold. T"·o and a half months before this a dmission, she had noted the sudden orl.set of diarrhea, which had pe~isted. She had from 15 to 20 ,,·atery stools daily, 5 or 6 of them awakening her from sleep at night. Because profuse diarrhea occurred after meais, she ,,·as afraid to eat, "ith a resultant 13.6-kg. i 30-pound j loss in weight. She had had no respiratory S)-mptoms or skin rash. For the pre,; ous 5 months she had no<ed a progressively enlarging nodule in the skin of the left-temple area. Physical examination re,·ealed a hard node, deep in the left side of the neck, and a raised, tender cutaneous le5io:I of the left temple, 1 by 1.2 em. She had no hea!"t ml.!ImUIS. A t)-pical carcinoid flush wo.s reproduced by the ingestion of a lcohol. Normal results were obtained from routine henl2;tologic studies and tests of blood sugar a~d urea, seru:n electrolytes, serum carotene, liver function, in~:luding alkaline phosphatase, proth rombin ~e a nd brom­sulfalein r etention. and from tests of thyroid function, in­c!uonlr basal me1:2bolism a nd protein-bound iodine. Chemi­ca! analyses of fecal fat sho,,·td that daily excretion ,,·as 3.2 gm. and that fat constituted 16 per cent of the total fecal solids. A u.ri::alysis for catechol amines ''o.s negath·e. A Ji,·er scan ,..;th !"''-labeled rose bengal ,,·as ,,-jthin normal limits. A proctoscopic e."':amination showed sacculation of the sig­moid and se,·era! di,·er.icula. A roentgenogram of the colon demonstrateC. d.h·enic-uJosis; roentgenograms of the stomach and small btMei were normal. X-ray study of the chest dis­closed fibrosis ar.d calcification in both apexes that had been present a:;d unchanged for at least 1 i yea.'>, ,,·h.ich was consistent with a pre,·iously known ruberculous infec­tion in 1920. Srudies pertinent to the patient's carcinoid syndrome are !ist.ec :n Table 2. On September 9, 1964, the skin ies.ion ,..:z.s excised, and h istologic sections r7(.ealed metastatic, Grade 3, solid carcinoma identical in structure ,,;:h the th)Toid tumor (Fig. lc ). Se,·en days late1 abdom­inal exploration re,·ealed multip le metastatic nodules, mt.a­suring up to I em. in diameter, in the right andlleft lobes of the Ji,·er. Tnere ,,-as a superficial, solitary 2-Cm. nodule in the oody of the pancreas. Both liver (Fig. ld) and pancreatic nodules ,,·ere similar in histologic stnfcture to chat seen in the thyToid gla:1d. A careful search/of the entire g-c..Strointestinal t:racet ga,·e no evidence of o/cinoid tumor,

I

246 rr..E ~EW E~GLA1'ID JOL"Rl~AL OF ~L~DTC~E July 29, 196

FtCt!RE I. Thyroid Carcinoma with Metastatic Spread (Hematoxylin and Eosin Stain X155) . a = the thyroid carcinoma. Note the regular nests of cells in a solid pattern. b = a metastatic deposit of similar tumor

in regional lymph nodu. c = a metastasis to the skin u/ the face. d = a metastatic deposit i11 the liuer.

and there was no involvement of the mesenteric lymph nodes. The appendix had been removed for acute appendi­citis in 1925. The concentrations of 5-hydroxytrypt::tmine (serotonin, 5-HT) in the metastatic lesions of the skin and liver are gi,·en in Table 2. Sero tonin was not detected in a specimen of nor.nal skin. After operation, the diarrhea and flushing continut.d, and the patient com;>la.ined of pain

in the right hip, A roentgenogram of the pelvis showed a metastatic lytic lesion involving the righ t innominate bone.

D rscussiO:-i

The '·malignant carcinoid syndrome" m this pa-

Xo. 5 }.fALIG!\:\.'\T C.·\RCJXOID S1"")."'DROME - ~10ERTEL ET AL. 24i

Am:)'s of 5-HydroxyindoZ.es and Histamine in G

"MG!ignant Carcinoid Syndrome" Associated u.:ith Noncarcir.vid Tumors.

per 24 hr.

j3.2, 41._; 42 .7, '">.7 ms. (nor­mal, <9 mg.)

:\one detect­able

:\ouc d<tect­able

10 Ulicrogm. (norrna.l, <<lO mi­crogm.)

Sot:acr.

BLOODt Ct."'TA..""1!.· OUS M.ttAS-

TASlSt

p~r mi. per gm.

0.6, 0.4 miao- 31.1 mi-gm. (nor- crogm. mal, <0.3 microgm.)

0.013 IWc:ro­gm. (nor­mal, <0.03 IDicrogm.)

Rt..P,TIC ~:;!':I!'-

Y.rl"AS• ''OL\-""0 TASJS! sru_...,._:

ptr fm.

63.3 mi- :\ O<>e crogm.. d!:-=­abl.e

5-HlAA measured by m elltod of Macfarlane et al.•; paper phic uudics of 5-bydrox)i.ndoles in ur~~ accor1iing to Smi1b,• revealed presenc.o or absence of 5-.H.J & 3-HTP. =>tioo of 5-HT in -.·hole blood ma.sured by melhod of Udto­t" t-.tion of 5-HT in lis$ue bom~enates determined ~ter pre­o! prutein.s as described b)· \\ ~h2ch et al. u foUo"'Cd br ietioo.u

definitely established. The attacks of arid the diarrhea ~,·ere both typical. Lab­results were like" -ise diagnostic, "ith con­high levels of 5-hydrox)-i.ndoleacetic aciC:

A.) in the urine and high Je,·eis of blood The onset of ·the carcinoid syndrome

to have been delayed until there were ex­hepatic metastases. ce· that this syndrome was not produced · ary carcinoid tumor is also strong, for observations, including abdominal explora­onstrated no such tumor. The most con-

ncling, however, was the very high serotonin of tumor regions that, histologically, ,,·ere e carcinoid type.

xact pathological classification of the tumor cult. Intestinal or bronchial carcinoid was

because the cells were con..c;jderably hu-ger tic figures were more numerous than would ted in a carcinoid. The time sequence in-

la prin1ary thyroidal neoplasm, with metas­regional lymph nodes one year later and spread to the lh·er, pancreas, skin of the d bone, sixteert months after the original :n. As a primary . th)TOidal lesion, the rumor resembled the subtype designated as "solid

:na with amyloid su·oma." Although zones of fibrosis were present, . classic amyloid char..ge king, and the degree of mitotic acti,-ity was at greater than in the usual carcinoma of !, but the histologic changes and the delayed netastasis did not favor a cliagnosis of ana­carcinoma of the thyroid gland. Metastasis hyroid gland from a small primary lesion in creas m ust be considered a· strong alterna-

tiYe possibility, espec:ally in ':ew of the fact that 2 of the other pre, ·iou:;l:- cited ca.<.es had a primary pancreatic adenocarcinoma. In our opinion, hO\,·­e,·er, the histology, the time Sb:!:.:ence and the pat­tern of metastatic ~pread tip?ed t.~c ~ca !es in fa,·or of a primary lesion in the thyroid g!and.

Some common denominator among the cases of noncarcinoid. tumors associated with the "malignant carcinoid syndrome" may be pre&nt. All the cases reported with known primary sources ha\·e origi­nated in ~sues deri,·ed from the entoderm of pouches of the primitive foregut - that is: pancreas, lung and th}Toid gland. T he possibility of a stem cell common to all these tumors, therefore, can be con­sidered.

Of inte...rest is the faet that 3 of the 8 patients had had other e' -idence of endocriJle hyperfunction. The p<!tient of Harrison and his associates~ had Cushing's :;:ndrorne, apparently related to an oat­cell carcinoma of the lung since the adrenal glands were normal at autopsy; the S2.Ille tumor presumably was responsible for the patient's '·malignant car­cinoid syndrome." The patient of '\-an der Veer and his co-workers! had an insulin-producing, malignant islet-cell twnor and had well documented hypogly­cemic attacks, the sa.rne rumor seemingly producing a carcinoid :;:-ndrome. The patient described abO'\·e had a parath~TOid adenoma "-ith hypercalcemia and was assumed to ha,·e hyperparath~Toidism. Al­though the possibility of coincidence cannot be de­nied, the odds against 3 such examples of endocrine hyperfunction oc~.ng by chance among 8 patients chosen at nmdom seem tO be a_~onomically high. Furthermore, a similar association of hyperfunction­ing end~rine tumors has been noted " itb bron­chial carcinoid rumors, 13 also derived from the prim­itive foregut.

As more cases of this kind are s:udied, these prob­lems mar be clarified.

A case im·oh-ing a metastatic 50lid carcinoma that was assumed to ha,-e its origin in the th)TOid gland and was associated ,,;th high rumor serotonin con­tent, hyperserotonemia and a "malignant carcinoid syndrome" is reported. In this ca.....;e a parath~Toid adenoma and byperparathyroidis::n were also noted.

Of the 8 cases (including the present case) of ·'malignant carcinoid syndrome" associated "ith noncarcinoid tumors no"· reported, 7 in ,,·hich the , pr.mary rumor " ·as kno,,-n rook origin in tissues/ ¥>-ith a common embn·ologic anlage. Three of these 8 patients also had ~ther condicioru of endocrin~ hyperfunction. ; '

R:r:rr:ru:..~cES

I. Mdfuilen.' F. F., Jr . . :wd H.aruoo, a H. Excessi-"t uru.J 5-h~dro.~·-3-iodoJt! a~tic acid i:l a.bseoce <i_ me-wtatic carcino:cl

c;,...,.... " '"""'· ''"'· I .

2-i-8

2 Dencer, H. Ar:o;>;.6~ Ca--cinoidsrndrom mir v~!!nn -~.,._ schetdung von 5-H!C:-ox-;ioeoles!i!!S"\!tt bei P=l._~inom. K lrn. W ch lt.Ich r. 37 :12-+5-12.;3, !959.

3. \~ Ce-r V~r-.. f. 5 . . "!t a!. ~le!:1SusisinJ ~lct-<e-11 ruroour c-i p3ttcre::u a.ssoci:ued •-.-ith h~~ and c:::Lrcinoid ~"Tldro~- 1A1tc1t I : H i"-1+19. !9';+.

4. Fbrri.«>n. ~- T ., ~Ionqomay, D. :\. D., R:>..ll:lky, A. S . . Robert­son , J. H .. and \ ' e!b-OOLrn . iL B. Cu~h.in!<"s S)-ndrome -.,; u, carci­noma. of brooci:n!$: and wit:b ieal'll.N!S suggesting carcinoid tumour. l..cnu t 1:23-25, 1357. -

5. ,,~illi3ms. .E. D~ and .-\z:zooudi. J. G. Tumours of l=g and car­cinoid sy:xlrome. T lwr= IS :3:l-36, 1960.

6. Qo,.·enlock.. A. H., Platt. D. 5 .. CunpOdl, -~- C. P .. and Worms!~. K . G . O:u<eD c::>.rO>oma of bronchus S«nting 5-l>;d;oX')'tl'"fptc>­plwl.. Lmtut 1 :3M-Sf..6, 1~-

7. S mit!>. A. ~ •• a al. Further obseJ-,..,.cioJ:IS 0 11 endoa'..ne ~ of argu t:lffinom:;o.. S=t:Wt: M . ]. 2 :2+--33, ~i.

July 29, 196)

3. ~be_£7!an.e. P - S., er al. E nd_ocn ne ~ o_l ~ntaffinoma • 'P~i"' =rr.:::~ce <() us.. of . ~na..ry >-ny~o~_ndolt<lcetic •cid -:;t "'-"!'oM .:1 c t:.gnostS. Scotttsn .\f. / . I : , -13- IJJ , 1956.

9. Smtth. I. C Ju ,Jmtttotraphic t:!'l d lltt!Mphf,die T , cJ111iquu Vtl,. 1.. 51i }'? - ~~w \_'~rk: lnterscit nce. 1~_.. • ·

10. {;d<nlnend, :> •• II etssbach. H., and BI"'<!tc. B. B. Assay of ...-.,. n in 3nd : tl.:ttetl metabolic.,;. enl}'"l'nc> and dnn<S. In Glici, Ll .\fttirods oi Biochemical d nalyris. Vol. 6 . "•w York · Inte~ 1953. P. 95. - •

I I. Weissba0. H., W~alkes. T. r: .. an~ vdeofnend. S. SimpliSo.! rot·t ht:-d tor .mf'3Su.nn$ set:o torHn 1n. t"s$$Ud: Simultaneous a.ss.t• d both serotom:o and h<S!o.rnmc. ] •. Brol_. Cht m. 230 :805-871 , 1954.

! ~ . Bogd•n>ki. D. F., Pler.scher, :\ .. Broclie. B. B., and l,;denfriend, S. fdtntifia;:'on and as;"Y of ~erotonin in brain. ] . Pltar-ol. ;,' E.xper. Tur~p- 117:8- -88. !9J6. •

13. WiUb.ms. E. D., and Cd ostin, L. R. Association o£ bronC;.; c:>rc-i!loid = d plurig'.andul:tr adenoma1osiJ. Thotaz 17 :1~127.. 1962.

V ASCUIAR LESIONS CAUSING HYPERTENSION IN NEUROFIBROMATOSIS*

MoRDECAI R .u.PERN, -~LD.,t Al'o""D Gumo CuRRARINO, M.D.t

NEW YORK CITY

NE'l'"ROFIBRO~B.TOSIS is a congenital and heredita-ry cfuorder involving ectodermal, neu­

roectodermal and mesodermal ti.s:.--ue. Cafe-au-lait spots, cutaneous neurofibromas, tumors of the cen­tral and peripheral ner\"ous systems, skeletal cilanges of scoliosis, orbital-h·all defects, pseudarthrosis and gigantism are ~well known manifestations.

The occurrence of vascular lesions is less well known but has been described by a number of authors.~-+ These va_-<.eular changes are said to pre­dominate in the kidne~-s, endocrine glands, heart and gastrointestinal rrac:, and ma~- lead to arterial stenosis or obliteration of the ar.erial lumen. Wh en these "·ascular lesions oi neurofibromatosis involve the abdominal aor ..a or the renal arteries systemic arterial hy;:>ertelliion rna~- result.

Two recent cases of neurofi bromatosis, hyperten­sion and renal-artery srenosis ba,·e been studied a t the Xew York H o:.--pital. We have also obtained additional information by re'l.i e,ying the case report­ed from thi5 w.stirurion by Gl.enn et a J.S in 1932. We ha,·e been able to find only 7 similar cases in the literature, the details of which are gi'l.·en in Table 1.

C -\.SE REPoRTS

C ... SE; 1.~ A 19-year-old woma n presented ger:eralized neurofibroma tosis maniiested by caie-au-!ait spoLS, m ulcipl!' neurofibromas a nd m ocerat.e scoliosis. ~!u lriple facial he­mangiomas present a t bir.b !a ter coalesced to crea te dis­figuration requiring~ r epe:it:r:e !acial surgery. Se,·ere sys temic hrpertension i.'1 the ra:-:ge oi 230/120 in th e upper ex­tremi ties and 150/ 120 in ±e !o" ·er extremirie;; had been recognized for 10 yea:-;;. I mra·.·enous and rerro~ace aortog­raphy re,·ealed a fu.; iiorm narro,,-ing oi the lowe!' moracir a nd pro:--.. imal a bcion ina l :u:.:-;a ir.·:ohing L~e ceEac ?-xi->, ,,; th extension do,,·:l o:o ~e re::~l a.."teries. .-\ large a.TJeurysm <l f the proxlica! portion of t::e right renal artery ,_..;.~ p re;em.

Operation co mi..,-.:ed of a ~:--pass of the coarcted segment

•From the Departmen t of RX:o!ogy, " • "· York Ho,7it21--Cornell ~fccii...a.l C<m er. ~c!•d by a ~t irom the ' ' rut•ha!l Fou.ndatioo.

t .\l$ocl.'1te p:o[d>C,r oi n>diology, Cornell l:ni,·ersk~- ~!e-dical Coll•ge. !P....eviously rr~on-e-d by Glenn rot ar.s

of the aorta utilizing the splenic artery. A tuft of den.sd. adherent fibroric tissue surrounded a nd constricted the aom at the le•·el oi the 11 th and 12th thoracic segment5. IE. tologically, thi.s was composed of fibrous and nerve tissur diagnosed as neurofibroma. Xo a ttempt was made to li.J> preach the renal-artery a neurysm. After operarion the blood pressure '~as recorded as H0/ 90 in th~ arms a nd 1+0/ 100 in the legs. O ne year later the patient died of cardiac arrest after plastic surgery for: a facial neurofibroma.

CASE 2 . .-\n 18-year-old boy has had 19 admissioru ro the Xe"· York H ospital for con·eccion of disfiguring fl::i.lll neurofibromas. Facial "hemangiomas·· present at birth tn­larged and coalesced during infancy. and biopsy at -! )"CW

of age revealed ·a plexiform nturom.:l.. Xumerous cafe-w­lait ;pots were present over the bod:·. T he patient's mother also had neurofibromatosi; . Hypertension was first notrti a< the age of 3 Yz years, and in recent }"ears the Olvod pressure had ranged from H S/ 56 to 193/ 130. T he systc:nUc arterial hypertension had been rel:nh·eiy unaffected oy anli­hn>ertensi,-e therapy during the last 5 yea rs.

Pertinent studies performed during the repeated hospiol admissioDS re,·ealed no1mal excretory urograms at the <1!"< of -! and at the age of 12. Fractional intravenous and ~m> grade pyelosrrams a t 13 a nd H years of age were normal .-\t that ~e a radioisotope renogram ,,·as interpreted lla

gi,·ing no e..-idence of unilatt ral reno,·ascular dysfu."lctoc:. Differential renal-function studies "·~re normal at LI-te ~ga of 1-! and ! 8. .-\.11 biochemical and bbrorarory studies, iD­cluding an a ngiotensin assay. were within nonnal limiD:

O n percu:aneous tramfemoral renal aortography iDtl selecti,·e renal arteriography performed in 1963 (Fig. l l the proximal half of the r ight main renal artery was ~ sent. R enal o!ood flow on this side ,,as provided br ~ lateral char.nels from the 12th intercostal artery, the m­temal spermatic artery and the retroperitoneal renal arte~ plexus. Stenosis of the left maio rena l artery, witil ! aneurysms distal to rhe stenotic segment. was ob;e!\tli Operat ion "a; contraindicated by rr.e complexity of U:< rer.al arterial lesions.

c .... s::: 3. :\. 3~ -year-o !d girl \\"l'.S admitted to the ;-;.-. York Hospi:al in 196+, when systemic arter ial h~·peneniia:> { IJ!ood prem ue of !50/ 11 0 ) ,,·as detected during the coun< of rout in~ ioJ.:-_.-.,·-up observation of a kuo" n srstol ic munu111

of no defi:U;e significance. Birth and ce,·ebpmeut haJ !:«-> nor:na l. Caic-au-iait spots were pr.-sent o\·er the trunk ;u;G

extremirie~, ·,,·irhout as3ociated skin ::odulcs. .-\ comp:c~r radio;: raphic s~eleta ! exai'T'inat ion rc\ ealed mild sc."\Uup~ of the ante:ic·r margins of rhc -!:.b through 9th th.J~ segments. Tn~ patient's father a !3o showed caie-au-b>: spots but no other m anifestation oi neurofibromatOsis.

Routine !?.hora tory swdie$, blood chemical findings ~...! c:ucchol amine de termina tions " ·ere ,,·1thin nonnal li!tu~ Fractional intravenous pyelography showed normal anc