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-v HUMAN PATHOLOGY-VOLUME 5, NUMBER S May 1974 is nonobstructive and is considered to be a developmental anomaly. In the case under discussion, infundibular stenosis was limited to the left kidney, which weighed 175 grams. It was slightly enlarged, its surface was smooth, and the cortex was minimally reduced in width. The calyces were uniformly distended and communicated with a normal pelvis via small, round, sharply defined lumtna. Multiple small concretions lay in the lowest calyx. On microscopic examination of the calyces, the most significant finding was an increase in the size and number of the smooth muscle fibers of the lower calvccal sphincters. At this level the muscle bundles of the calyx and ad joining pelvis had a thick, coarsely woven texture (Fig. 1). The kidney parenchyma was well preserved, and in none of the sections was there any evidence of recent or remote infection. The available literature dealing with this restricted form of hydronephrosis caused by obstruction, whether functional or anatomical, is very limited, and in none or the reports has hypertrophy of the lower calyceal sphincters been mentioned. Although hypertrophy of the calyceal ring leading to infundibular steno sis might readily explain the hypertrophy and dilatation of the calyces, the actual mechanism responsible for this overgrowth of smooth muscle remains unanswered. Watkins.1 Moore.1 and Williams and Mininberg4 have suggested achalasia as a possible mechanism, but they were the first to point out that such a sugges tion is pure speculation. References 1. Puwu-n. -V.: L-c Mctfatiilice. J* 1`nd. Nephml. i ixw. 1. & WiifLin*. K. II.: CiMHiif ihc bdiw* ducmlndrtrjIinRii Bril, J, I'rtti., J J W7. IWW. i Momix'. 1.: ||\cInitalk'<Hii. Brit. J, I'rol., 22:.Kl4, IWftO* 4. Willumi*. 1). I.. ami MinmhctR. I). 1.: II wlnKAlnn**: i-pon of ihietr ill ihildmi. Brit. J. 1'iiiL. ItKjH. ESTHESIONEUROBLASTOMA: A LIGHT AND ELECTRON MICROSCOPIC STUDY Llonaku B. Kahn. M.B., B.Ch.. M.Med. (I'ATHOLtXiV)* Abttract The rleitron mmn.eojnr fratines of an olfartiny esthesionrliiohliistinna art1 ilesriihed. Thr laaitir rrlls Senior lecturer, [)c|>.imncjii ol . 364_ .. L'lmursily of (-I|x- 1`own Medical Sclmol. ( a[H* row,. South Africa. hint ur11 dnrlojied ueuritir jirarexset rontaimn lira> otuhnles anil nrumfiln il\. In addition, nrurt srrretory granules, similar la dune seen in adrem ' nrunddaslamas. werr jiresenl in the main cell baa as urll as in llie ueurilir jnoeesses. The netinh uere also well demonstrated try light miemseoft, examination when stained lix the Ptdmgren sills method. The nnjuntaare oj demonstration of thes //rneexses in rstaldislung a firm diagnosis is strexsei Election microscopic demonstration oj neurites an t serretnn granules in a nasal tumor is diagnostic 11 an esthesionenrablastunuL Only one other pa|>er could Ire found in the English literature in which some ultraitruclural features of a nasal neuroblastoma are illustrated.1 CASE REPORT _______ _ Te had no his tory of pain but had noticed a water)' discharge from the nostril and slight proptosis of his left eye. Two years previously he had had an operation on his nose in another country but. no further details are available. On examination a fleshy tumor was found in the superior part of the nasal cavity, it was filling the left choana and extending int i the |x>siiiasal space. hut no other clinical features T note. Tomograms showed a soft tissue mass i t the nasal cavity cut the left side and dcsiructio t of the medial orbital margin and possibly t f the medial wall of the left maxillary antrui t (Fig. I). All llie paranasal sinuses were notice I to be opaque. Tomography of the base of ll : skull showed no bony erosion and a bra1 i scan was unremarkable. A biopsy of the tumor was reported . > showing an undifferentiated carcinoma. A It t Caldwcll-Luc and left sphenoeihmoidecton were |x:i foi-med. The medial wall of the max - luty antrum was bulging into the antral cavil . which was free of tumor. The middle and i - ferior turbinates were removed, and turn lissue was excised piecemeal from the antcrit middle, and |xisterior ethmoidal cells. Ti sphenoidal sinus was found to be free of t - mor. Histologic examination demonstrate 1 tumor in all ihe ethmoidal cells as well as i die midtile turbinate. The tumor was aga > ie|xirted to lie an undifferentiated carcinom Three days later a left froiiiocthnioidecion was |>ei'formed and minor was removed fro I EPL 02290 *1 I MEDICAL INTELUCENCE r immediately transferred to phosphate buffered glutaraldehyde and postfixcd in Palade's solu tion. The tissue was tlien dehydrated in graded alcohols and embedded in Araidile. Uhrathin sections were cut. stained with aqueous uranyl nitrate and lead acetate, and examined with an AEI-OEC 6B electron microscope. Light Microscopic Examination (Fig. 2), whereas in others obvious infiltration of lamellar hone was noted. (Fig. 3). Within this stroma a few ducts and acini of minor salivary gland origin were observed. ......... - J Figure 1. Tomogram showing soft tissue shadow in the left nasal cavity, destruction of the -<icdial orbital margin, and clouding of the paia)aal sinuses. o*4 the frontal sinus. On this occasion a histologic ihagnosis of esthesioneuroblastoma was made. I t August and September the patient was ten a course of radiotherapy to a maximal t mor dosage of 5520 rads. He was then dis. 'arged. In Novemltcr he was found to have a polyp . ached to the right middle meatus. A 1.5 by 1.5 i i. polyp was excised and showed the features i an esthesioneuroblastoma. One week later iglu sphenoeihmoidectomy was performed, i .able tumor was found in the ethmoid and s removed from its attachment to the cribrim plate. The superior and middle turbinates I part of the vomer and rostrum were ex ,d. Three 10 mg. radium tubes were inserted > the region of the roof of the nasal cavity. .roscopic examination confirmed the pres4 1 c of tumor in the ethmoidal and sphenoidal uses. The patient was discharged nine days I t and returned home to Angola. In view 1 the extent of the lesion and failure of re fuse to radiotherapy, the prognosis was 1 iside.ed to he very poor. : tTHOLCKJY ethodt (10 per cent tormalin). 02291 HUMAN PATHOLOGY-VOLUME 5, NUMBER 3 May 1974 gpij 02292 * MEDICAL INTELLIGENCE Figure 5* ,4, Abundant delicate ncurofibrils form a meshwork within islands of tumor cells but are absent ip ''rovascukir septa. (PsilmgrevTs jiher stain. xgoo.) B, Coarse reticulin fibers in fibrovascubtr septa sur* r / islands of tumor cells but jre not present within these islands. ((jordon-Swcct reticulin stain. x20O.) Wli*5*WPt<i(PPwUSIWBBafc(FiK. 5.-0. icse fibrils were not present in the fihro-cular sepia, 1^--M^^MWiWLhe 'WMMHMMMlIPWMMPiVIMMnHMS i in the rnvascular sepia l>ui was completely aliscm ihin the cords and islands of lumor (Fig. 5/0. >e reticulin Risers were coarser than ihe urofibrils and tended to form bundles 'her than a delicate meshwork.* showed focal areas of thickening suggesting specialized surface attachment plates (maculae densae), but true desmosomes were not ob served (Fig, ti). (Figs. 6 to 8). When sectioned longi tudinally. they could he followed for a consid erable distance. They contained numerous fine filaments, which ran parallel to the long axis of the cell process (Figs. 6, 7). In trans verse section they appeared as dots of uniform si/e and rather evenly distributed (Fig. 8). | Figs. 6. 7). When sec tioned longitudinally, they appeared as a double layered membrane, whereas trans verse sectioning showed a ringlike structure (Figs. 6 to 8). Some neurnfilaments and tu bules were also present in the cytoplasm of the main cell Ixxly but in much smaller numliers than in their neuritic extensions.1 ectron Microscopic Examination The minor cells were compactly arranged, d ihe plasma membranes of opposing cells KFigs. 6, 7, Thegranules were round and fairly uniform in 30/ EPL 02293 Figure 6. Electron micrograph showing longitudinally sectioned ncurite w ith neurotubules (short arrows) and ncumfilaments in close proximity to secretory granules. Maculae densae are present between opposing plasma membranes (long arrows). (*32.300.) ) 368_ Figure 7. Electron micrograph showing longitudinally sectioned ncurite containing numerous fine neurt filaments and occasional neurotuhiiles (arrows). Secretory granules are seen in an adjacent cell body. (X70.000 EPL 02294 MEDICAL INTELLIGENCE Figure 8. Obliquely sectioned neurite in which some of the tubules appear as ringlike structures. (X40.0U0.) size, measuring up to 1000 A in greatest diameter. They had a distinct limiting mem brane and an electron dense core. A prom lent electron lucent area was present between ie limiting membrane and the electron dense >re. Within the cytoplasmic .processes the ranulcs were found in close association with ie tubules and filaments (Fig. 6). Cytoplasmic organelles were sparse. There ere moderate numbers of mitochondria and lated profiles of smooth endoplasmic reulum. The mitochondria were slightly entged and showed focal swelling of some of e cristae (Fig. 9). SCL'SSION > and was first 'trilled by Berger ct al.* in 19*24 under the e, "L'esthesioneuroepitheliome olfactif." tis tumor contained well formed rosettes. 19*26 Berger and Coutard* rejiot ted a varit of the abuse tumor and termed it "L'esvsioneurocytotne olfactif." This tuntor lacked rosettes. tomosing trabeculae of rather uniform cells. These mav resemble epithelial cells, as in our case, and be mistaken for an undifferentiated carcinoma, or they may resemble Ivmpht^ reticular cells and the tumor then may be misdiagnosed as malignant lymphoma. When present, rosettes are helpful, although even these may be mistaken for the glandular struc tures of an adenocarcinoma. We agree with Obert ct al/ that in the absence of neurofibrils a nasal tumor cannot be diagnosed as a neurt^ blastoma with certainty. Gerard-Marcham and Micheau* stressed that axons do not show up clearly in the usual routine staining methods, and they considered this to account for the fact that i7 of the 45 cases of csthesioncuroblastoma in the literature that they reviewed had initially been incorrectly diagnosed. The first two biopsies performed on our patient had also been incorrectly diag- 369 EPL 02295 HUMAN PATHOLOGY-VOLUME 5, NUMBER 3 May 1974 figure 9. Numerous membrane bound neurosecretory granule* in the ectoplasm of the tumor cell. Mitochondria are enlarged and show focal swelling of some of the crime. (*70.000.) nosed as undifferentiated carcinoma. Although most cases in the literature mention the pres ence of fibrils or fibrillar material associated with the tumor cells, we have been disturbed by the frequency with which these fibrils have been accepted as neurofibrils on the basis of hematoxylin and eosin staining alone. The Palmgren silver stain for neurofibrils con clusively demonstrated a feltwork of neurofibrils associated with the tumor cells in our case, and contrasted well with the reticulin stain, which demonstrated only connective tissue fibers in the fibrovascular stroma. McC.avran* also stressed the difficulty in recog nizing this neoplasm and suggested that ultrastructural examination, even of formalin fixed tissue, could l>e of considerable help. presence of neuritic processes arising from the tumor cells. These processes are charatterized by the presence of an admixture ol neurofilaments and neurotubules. In additioi . the cytoplasm of the tumor cells contains mod erate numbers of neurosecretory granule . these are also present within the neuritic pro esses. The presence of neurosecretory grai ules and neuritic processes has also been dei onstrated ultrastructurally in adrenal neur blastoma cells and chick embryo and svi pathetic ganglion cells grown in vitro* T! granules in the nasal tumor were about n ' same size as those in the cells from the syntp thclic ganglia and from the neuroblastoma h ' smaller than those noted in pheochromocy tot i cells. In that pa|ier the presence of numer ous cytoplasmic processes and membrane bound neurosecretory granules was demon strated in sections prepared from formalin fixed tissue. The nature of the cytoplasmic processes was not discussed and they were apparently not recognizable as axons. Our 3/0 electron microscopic studies demonstrate the Neuritic processes were noted in the nw . differentiated neuroblastic cells as well as > the mature ganglionic type of cell. Morpholi - ically similar granules have been found i the carotid body and glomusjugulare tumor 1 The membrane bound dense core granu s seen in carcinoid tumors of the alimenta v EPL 02296 MEDICAL INTELLIGENCE i jet are similar bul tend to be larger and more I Icomorphic and are not associated with neuroI laments or neurotubules.11 Our electron i licroscopic findings thus confirm the neurog< lous nature of the tumor and its resemblance | t i the adrenal neuroblastoma. The presence i I' dense core neurosecretory granules suggests l ie possibility that some of these tumors may I I c found to produce catecholamines. 1 Kolze'* found the urinary level of 3nicthoxy-4-hvdroxyniandelic acid to he normal in a patient with an olfactory estheskmeurobfastoma. Unfortunately urinary catecholamine levels were not determined in our patient, but this test should be performed in all pa* ticnis suspected of having this tumor. It would also be interesting to see whether future ultrastructural studies of this tumor confirm the existence of several histologic variants. of Loci of the nervus terminals, a structure composed of sympathetic fibers and ganglion cells in the anterior aspect of the olfactory mucous membrane.1* Origin from the organ i of Jacobson11 and the sphenopalatine gan glion1* would anatomically be inconsistent j - S} that of the majoritv of the tumors. ! mJSSSSSSSSSSSSm a ;d were noted in three of 18 cases reported I Hutter et al.TM In I`.)66 Skolnick et al." | evented an extensive review' of 97 cases. < rvical node metastases occurred in 11 pa< ms and distant metastases in II. The lung v i the most frequent site of distant meiasi es. Schenck and OguraTM noted cervical i te metastases in three of eight patients seen i heir institution over a 22 year period. The effectiveness of therapy is difficult ' issess because of the relatiiely small num1 of cases reported. The extensive review ' skolnick et al.1* demonstrated a 52 per cent I - sear survival rate in 50 patients who had I n followed for five years or more. They > immended surgical resection as the treat1 it of choice with irradiation reserved for I 'istence of tumor. However, the tumor is < med b\ some authors to l>e fairly radio' 'itive so that local excision followed by 1 nation therapy is frequemlv recotni ided.1-1,111 No convincing relationship I Iteen demonstrated Itetwecn the histologic J 'earance and the prognosis. Acknowledgment 1 wish to thank Mr. John Dale, Mr. Tony Visscr, and Mr. Malcolm Emms for technical assistance. Reference* 1. CjJiro. 1-, de la P*va. S.. and Webster. J, H.: Eithni neuroblastoma--a report tf 7 cam. Amer. J. Rocm- gemd.. M l. I9N. 2. McCavran. M. H.; Neurogenous nasal neoptaM. Ann. OtoC 79:347, 1970. 3. Drury. IL A. B- and Wailington. E, A..* Carkua'i Hiuologicai Technique, Ed. 4. New York. Oxford L'niversky Press. 1962. 4. Better. L_ Luc. and Richard: L'esthfsioneimdps- ihcliome nlfactif. BulL Awoc, Franc. Etude Cancer. /5;4IO. 1974. 3. Berger. L, and Coutard, H.: L'euhhnnniniciloiM ojfaciif. Bull Assoc. Franc. Etude Cancer, /5:404. 1930. 6. Fisher. E. R_: Neuroblastomas of ihc nasai fossa. Arch. Path.. 60:433. 1935. 7. Ohcri, 0, j.. Devine, K. D., and McDonald. J. R-i OUk* lorv neuroblastomas. Cancer. 75:203, i960. 8. GerardAfarchani, R.. and Micheau. C.; MicroKopkal dtagmii of olfactory mhesioneuTomas--genrrai review and report of 5 case*. J. SaL Cancer Inauuu*. 75:75, 1963, 9. Kadin. Nl. L, and Bemch. K. G.: Comparison of phe^ chromocytes i(h ganglion cells and neurobiastt grown in vitro--an electron micnwcnpic and hkfr chemical study. Cancer. 27:1148, 1971. ID. Mnugi. K., Mwugi. X., and Newton. W. A.: Fine sanac* turaJ study of neuroblastoma, gangliooeurohlainima and phcochromucytoma. Arch. Path.. #6:160. 1966. M. Balogh. K.. Jr.. Draskoczv, P. R,. and Caulfield, J. B-; Norepinephrine in turnon of the jugular |jonia (abstracted). Amer.J. Path.. 4#;40A, 1966. 12, Black, W. CLi Enierochromaflm cell types and corre- spending carcinoid (umon, Lab. Invest.. 79.473.1966. 15. kolze, V.: Olfactory cstheMoneurobUsioma. Ada Otolarvng.. 65:397. 1968. t4. McndckifT. J.: The olfactory neuroepithelial tumors--* review of the literature and report of 6 additional cases. Cancer. 10:944, 1957. 13. Skutivkk. E, M-. Masaari. F. S., and Toma. L T,: Olfactort' neuroepithelioma -- review of the world literature and presentation of 2 cases. Arch. Otolarvng- #4: 644. 1966. 16. Manin, J. F.. Dargent. M,, and CignouiL M*: Les (umeurs nerveuses dcs fosses nasalo. Ann. Otolaryn (Paris). 66:18. 1949. 17. Scliall. L A., and Uneback. M.: Primarv intraaasal neuroblastoma-- repon of 3 cases. Ann, Oui. 60: 221. 1951. 18. Escat, .. Lr iimpathome spheivwdo-ethmordal n'ayrah pas von point de depart dam le ganglion tpheno (Nilatinr Origine suggenre par 2 observation*. Ann. Otolaryng., 8:828. 1931. 19. Hutter, R. V. P.. Lewis. J. S.. Foote. F- W,, and TuOefsen, H. R-: EsihevoneuroWasioma -- a clinical and patho logical ntudv. Amcr. J- Surg.. 706:748, 1965. 20. Schenck, N. L, and Ojtun. J. H.: Esthcstoneurobla*-*. ioma*-an enigma in diagonals, a dilemma in ireasmem. Arch. Otolarvng,. 96:322. 1972. 21. A*h. J. E.. Beck. M. R.. and Wilkes, j. W.: Tumors of the L'ppcr Respirators1 Tran and Ear. Allas of Tumor PaihoJogv, Washington. D.CL, Armed Forces Institute of Pathology. 1964. Sec. IV. Fates. 12 and 13. 371 l I | i 02297 epl