FROM T H E DEPARTMENT OF PATHOLOGY, T H E FINSEN INSTITUTE AND RADIUM CENTRE, COPEh'HAGEN (DIRECT'OR: J . CLEMMESEN, M.0.)

A CASE OF CARCINOMA ADENOIDES CYSTICUM ARISING IN THE SPHENOID SINUS

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PETER MEYEH I<eceived 6.ii.62

Among tumours originating in salivary-gland tissuc thcrc a rc a few whosc peculiar histology and charactcristic clinical coursc have given risc to numcrous actiological hypotheses, and yct their gcncsis still rcmains obscure. This applies to niixcd tumours as wcll as to adcno- lymphonia and carcinoma adcnoides cysticum. Thcsc tumours occur chiefly in thc largc salivary glands, but may also originatc in other glands of thc upper digcstivc tract and air passagcs. Frequently they arc located in the latcral wall of the nasal cavity, including thc maxil- lary sinus, and in the rhinopharynx, far less commonly in the frontal or sphcnoid sinuscs which norinally hold only a few glands of littlc activity.

Carcinoma adcnoides cysticuin (c. a. c.) is a rare tumour. Its histo- logical architccture is pcculiar, inadc up of islets of small, dcnscly placed, hyperchromatic cells of the basal typc surrounding a cystic cavity with eosinophilic sccretion. Thc islets a re situated in a more or lcss hyalinizcd conncctivc tissue. - The names applicd to this form of tuinour in thc course of time rcflcct the hypothcscs on its gcncsis: Bitfroth (1859) used thc term cylindroma, Krompecher ( 1918) basa- lioma, and othcrs, int. al. Barmwafer (1931) cndothclioma. I t w a s not until 1935 that Ahlbom isolated c. a. c. as a spccial typc of carcinoma, bclicving that i t was dcrived from the cxcretory ducts.

Ringertz (1938) , in a scrim of tuinours arising in thc nosc and nasal sinuscs, found a total of 8 cases of c. a. c. in addition to 4 hcnign cystic basal-cell tumours. From thc litcraturc hc collectcd also 52 eases of c. a. c. arising in the nose, maxillary sinuses, and ethmoid cells. Ac- cording to modern criteria, hc found several of thcsc reported cases to be doubtful, as c. a. c. was not isolatcd as a spccial typc until 1935. - C. a. c. arising in the frontal or sphcnoid sinuses has not becn re- ported. Since, howevcr, tumours arising in the uppcr posterior part of the maxillary sinuses, the posterior ethmoid cells, or in thc sphcnoid sinus a rc indistinguishable from each other in thc advanced stage bc- cause of early bony destruction, some tumour in the niaxillo-cthmoid

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rcgion niay have originated from the sphcnoid sinus. Geschickter (1935) described 15 cases of c. a. c. one of which extcndcd intracrani- ally froni the rhinopharynx. Godtfredsen ( 1944) reportcd 5 cylindro- inas arising in the rhinopharynx, 4 of which showcd intracranial in- vasion. Vald. Poiilsen (1953) described 2 adcnoniatous carcinomas in thc cthnioid sinus, both invading the dura and one of thcm croding the left cavernous sinus.

Thc syinptonis and signs of malignant tumours arising supero-po- steriorly in the lateral wrall of the nosc arc fairly charactcristic, varying but little with the type of tuniour. Swelling of the nose or rhinopharynx is an carly sign. Intracranial extension is rare, but if prescnt it is oftcn pcrincural through the foramen ovale, foramen rotundum, or foramen laceruin. The symptoms from the cranial ncrvcs often occur in a parti- cular scqucnce: The initial symptom will bc neuralgia affccting the 2nd trigcniinal branch which makes thc patient consult the dentist (Ohngrerz 1933). A t an carly stage all thc trigcminal branches and the nervcs of the ocular muscles become involved. Godtfredsen dcscribed as a special, rather uncommon syndrome, siinultancous involvcmcnt of thc trigciiiinal nerve, nerves of the ocular niusclcs, and hypoglossal nerve. C. a. c. is reported to show a fairly markcd tcndcncy to infiltra- tivc growth, oftcn niultifocal, but with late metastasization. Its growth is mainly cxtradural.

The prescnt case of c. a. 6. is of intercst for several reasons: Most probably it arose in the sphenoid sinus, it showcd pronounced invasiw growth with nionstrous changes in the base of the skull and invasion of thc central ncrvous system. The history was short and atypical, giving rise to a numbcr of diagnostic difficulties.

C A S E R E P O R T

Hadium Centre 108016. Path. Dept. 95/61. A housewife, aged 63. In 1952 syphilis was diagnosed and treated, in May 1960

cholecystectomy. Otherwise in good health, in particular she was not very prone to colds or sinusitis.

In June 1959 mild paraesthesiae in the left half of the tongue. One month later paraesthesiae, reduced sensibility and sense of taste i n the right half of the tongue. In August 1960 out-patient X-ray examination revealed a cystic, ill-defined trans- lucency in the left lower jaw, but no other abnormalities of the upper or lower jaw.

In September 1960 neurological examination showed disturbance4 of sensihility in the areas supplied by the 2nd and 3rd branches of the trigeminal nerve as well as paresis and atrophy of the right half of the tongue. The patient was admitted to hospital where right-sided preponderance of deep reflexes and involvement of the right accessory nerve were found. The rhinopharynx and X-rays of the hase of the skull were normal, b u t pneumo-encephalography revealed a left shift of the fourth ventricle. The patient was transferred to a department of neurosurgery, where she was submitted, on Oct. 31st 1960, t o craniotomy with exploration of the right posterior cranial fossa as f a r as the trigeminal nerve and internal acoustic meatus. The dura covering the base of the skull and the trigeminal cave were left intact. N o abnormality was found.

One month later the patient developed acute right-sided facial palsy suggesting a lesion hetween the nucleus and the geniculate ganglion. Acoustic-vestihular findings normal. Heduced corneal sensibility on the right. In the course of the subsequent

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months total paresis of all of the muscles of the right c ~ e developed. The patient was now suffering from right-sided headache, difficulty of walking, and vertigo of a gyratory type.

In July 1961 she mas re-admitted, now with hard, non-tender lymph nodes helow the right mandible and in the right supra-clavicular fossa. X-rays showed advanced destruction of the hasc of the skull, from the orbit to the foramen magnum. A biopsy from the swelling in the right temporal region rcvealcd carcinoma adenoitles cysticum, and the patient was transferrcd to the Radium Centre for X-ray therapy.

With increasing signs of cerebral involvement 5he died on Aug. 29th 1961.

Thus, the disease had run its course in a little over a year, munifcsting itself as successive signs of neurological loss, first involving the 2nd and 3rd trigcminal branches, thc hypoglossal and accessory nerves, thcn thc facial nerve, nerves of thc ocular muscles, and the first trigcminal branch. Signs of elevated iiitracranial pressure and regional metastases did not occur until a t a late stage.

Post-morfem findings: In the right medial and posterior cranial fossae a coarsely lobulatcd tumour, 10 x 8 x 6 cni, inhomogenous on section, in places nccrotic and invading hlood vessels. Pronounced destruction

Fig . 1. 13ase of the skull : Theca removed, hrain and brain stem removed, du ra intact except at the si te of the right posterior fossa. Neoplastic masses on the right, from thc roof of the orbit to the right transverse sinus. Destruction of the right squama temporalis.

Fig. 2. Photomicrograph of the relation o f the tumour to the rhinopharynx: Hyalinizcd conncctive t issue 1,etween t he mucous membrane and the polymorphous tumour

masses.

Fig . 3. Invasion of the molecular layer of the cerebellar cortex.

Ncrvc cells partially necrotic.

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Fig. 4 . Islet of typical tumour cells. In places imitation o f glandular lumina.

F i g . 5. Metastases to the fa t ty t issue surrounding the right carotid sheath.

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of bone. The tuniour was chiefly cxtradural, but in a few places it had invaded the dura and the central nervous system.

Its demarcation was as follows: Anteriorly it had invaded the orbit, the posterior ethnioid cells, and the maxillary sinus which was not, however, quite filled. Medially, the tumour exceeded the midline, de- stroying the entire body of the sphenoid bone and the right half of the basilar par t of the occipital bone. The cavernous sinus was destroyed, the pituitary gland intact, entirely surrounded by tuniour tissue. Later- ally the tuinour extended to the lateral wall of the medial and posterior fossae, destroying the bone and invading the temporal muscle. The medial part of the pyramid was destroyed, while its lateral part with the labyrinth was intact. The petrous and the cavernous portions of the internal carotid artery were entirely surrounded by tumour tissue. Caudally the turnour extended to the parapharyngeal space, destroying the pterygoid process. On the other hand, there was no tumour tissue i n the rhinopharynx whose mucous membrane was intact, also on microscopic examination. Cranially the tumour extended approx. 4 cni past the level of the base of the skull, filling the entire medial fossa, the greater part of the posterior fossa and ensheathing all of the cranial nerves except the first. I t had made a distinct impression into the brain which was shifted far to the left. Posteriorly, a t the site of the inferior surface of the cerebcllum, small ulcerations in the dura with tumour invasion of the pia.

Hard, adherent lymph nodes under the right mandible, in the supra- clavicular fossa, and along the vcsscls of the neck.

In the lungs basal congestion. No metastases to the thoracic or ah- dominal organs or lymph nodes.

Sequelae of cholecystectomy. Microscopic examination: The tumour (fig. 4) consisted of islets and

strands of small, oval to round, epithelial cells with sparse cytoplasm, dark, fairly uniform nuclei, and a number of mitotic figures. While peri- pherally there was little cohesion between the cells, they were more densely placed towards the centre. Centrally in the islets in several places irregularly demarcated cavities containing eosinophilic, finely granular secretion or blood. The islets were seperated by vascular, connective tissue, infiltrated by lymphocytes. - The appearances were highly varied, showing invasion of vessels, bone, muscles, cerebellar tissue (fig. 3 ) , choroid plexus, the membranes around the pituitary gland, and the central nervous system. The pituitary gland and rhino- pharyngeal Inucosa (fig. 2 ) were intact.

The metastases (fig. 5 ) showed a more monotonous and typical ap- pearance, lying in the specimens available in fatty tissue and in a peri- neural situation, not in lymph nodes.

Summing up, the tuniour was the shape of a cone with its top in the sphenoid sinus and its base a t the site of the temporal fossa. It was

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highly dcstructivc, invading vcsscls, but had littlc tcndency to mctasta- s i x . Owing to thc widcsprcad honc destruction, i t is iniyossihlc to locatc thc origin cxactly, but thc scqucncc of thc symptoms and signs, thc in- tact rhinopharyngcal mucosa, and the abscncc of tumour tissuc in thc antcrior part of the maxillary sinus indicate an origin from tlic sphc- noicl sinus. - I t has prcsumahly first sprcad cxtradurally to thc latcral and posterior aspect along the infcrior petrosal sinus to thc jugular foramcn. Latcr, i t has propagatcd on hoth sidcs of thc right pyramid which was not dcstroycd until a latc stage. The marked sprcad i n thc posterior fossa and thc invasion of the dura a t this sitc were possibly due to thc right-sided posterior craniotomy which has partially broken down the dural harricr a t thc sitc of the foratncii magnum.

s u BI ni A H Y

This is a dcscription of a short, atypical history of carcinoma aclc- noidcs cysticum, which prohably arose in thc sphenoid sinus, dcstroy- ing thc hasc of thc skull.

H E FI3 R E N C I ? S

A hlbom, H . E.: Mucous and Salivary Gland Tumours. Thesis, Stockholm, 1935. Acta radiol. suppl. 23.

Barmcuater, K . : Einige FIllc von Endotheliom in den oheren Luft- und Speisewcgen. Acta otolaryng., 16: 1,1931.

Hillroth, T h . : Heobachtungcn iiher Geschwulste der Spcichcldriisen. Arch. f. pathol. Anat. u. Physiologic, 1 7 : 357, 1859.

Geschickter, Ch. F . : Tumors of t he Nasa l and Paranasa l Cavities. Am. J. Canc.. 24, 2: 637,1935.

Godtfretlsen, E . : Ophthalmologic and Neurologic Symptoms of Malignant Naso- pharyngeal Turnours. Thesis, Copenhagen 1944.

Krompecher , E . : Z u r Kentniss der 13asalkrebsc der Nasc, dcr Nehenhiihlen, d e s I<ehl- kopfcs und der Trachea. Arch. Laryng-llhinol., 31: 443,1918.

Poulsen, 17.: Malignant Tumours in Nose and Paranasa l Sinuses. Acta oto-laryng., 43: 474,1953.

Ringertz, N.: Pathology of Malignant Turnours Arising, in the Nasal and Paranasa l Cavities and Maxilla. Thesis. Helsingfors 1938. Acta oto-laryng, suppl. 27.

Ohngren, L. G.: Malignant Tumours of t he Maxillo-cthmoidal Ilegion. Actn oto- laryng. Suppl. 19, 1933.