Salivary Gland Radiology

salivary glands radiology

Definition of Salivary Gland DiseaseDental diagnosticians have responsibility for detecting disorders of the salivary glands A familiarity with salivary gland disorders and applicable current imaging techniques is an essential element of the clinician s armamentarium .

Salivary gland diseaseClinical Signs and SymptomsDiseases of the major salivary glands may have single or multiple clinical features.Pain and altered salivary flow may be present. The periodicity and longevity of these symptoms are important in the differential diagnosis, a review of the medical history and physical condition of the patient may provide important information.Differential Diagnosis Parotid Gland Area- of Salivary EnlargementsDifferential Diagnosis Submandibular Area- of Salivary EnlargementsApplied Diagnostic Imagingof the Salivary GlandsDiagnostic imaging of salivary gland disease may be undertaken to differentiate inflammatory processes from neoplastic disease .diffuse disease from focal suppurative disease, identify and localize sialoliths, and demonstrate ductal morphology anddetermine the anatomic location of a tumor, in addition , differentiate benign from malignant tumor . PLAIN FILM RADIOGRAPHYPlain film radiography is a fundamental part of the examination of the salivary glands and may provide sufficient information to preclude the use of more sophisticated and expensive imaging techniques .It has the potential to identify unrelated pathoses in the areas of the salivary glands that may be mistakenly identified as salivary gland disease, such as resorptive or osteoblastic changes in adjacent bone .

PLAIN FILM RADIOGRAPHYPanoramic and conventional posteroanterior (PA) skull radiographs may demonstrate bony lesions, thus eliminating salivary pathosis from the differential diagnosis.

Unilateral or bilateral functional or congenital hypertrophy of the masseter muscle may clinically mimic a salivary tumor. A plain film extraoral radiograph may demonstrate a deep antegonial notch, overdeveloped mandibular angle, and exostosis on the outer surface of the angle in cases of masseter hypertrophy.

Plain film radiographs are useful when the clinical impression, supported by a compatible history, suggests the presence of sialoliths (stones or calculi).INTRAORAL RADIOGRAPHYSialoliths in the anterior two thirds of the submandibular duct are typically imaged with a cross-sectional mandibular occlusal projectionThe posterior part of the duct is demonstrated with an over-the-shoulder occlusal projection view, where the directing cone is placed on the shoulder and central ray directed in an anterior direction through the angle of the mandible, with the patient s head tilted to the unaffected side and rotated back .Parotid sialoliths are more difficult to demonstrate than the submandibular variety as a result of the tortuous course of Stensen duct around the anterior border of the masseter and through the buccinator muscle. As a rule, only sialoliths anterior to the masseter muscle can be imaged on an intraoral film. Underexposed mandibular occlusal radiograph demonstrating radiopaque sialolith inWharton duct. Note the classic laminated appearance.

Periapical radiographs of the same case. Theradiopaque calculus can be localized lingual to the teeth by applying appropriate object localizationrules

An axial bone algorithm CT image showing a sialolith in the submandibular duct (arrow).

EXTRAORAL RADIOGRAPHYA panoramic projection frequently demonstrates sialoliths in the posterior duct or reveals intraglandular sialoliths in the submandibular gland.The image of most parotid sialoliths is superimposed over the ramus and body of the mandible .To demonstrate sialoliths in the submandibular gland, the lateral projection is modified by opening the mouth, extending the chin, and depressing the tongue with the index finger.EXTRAORAL RADIOGRAPHYSialoliths in the distal portion of Stensen duct or in the parotid gland are difficult to demonstrate by intraoral or lateral extraoral views. However, a PA skull projection with the cheeks puffed out may move the image of the sialolith free of the bone .Stereoscopic panoramic plain filmprojection.

Over-theshoulderocclusal projection revealing a sialolith.

Anteroposterior skull view with cheek blownout to provide air contrast to reveal a parotidsialolith (arrow).

CONVENTIONAL SIALOGRAPHYFirst performed in 1902, sialography is a radiographic technique where a radiopaque contrast agent is infused into the ductal system of a salivary gland before imaging with plain films, fluoroscopy, panoramic radiography, conventional tomography, or CT. Sialography remains the most detailed way to image the ductal system . The parotid and submandibular glands are more readily studied with this technique.A survey or scout film is usually made before the infusion of the contrast solution into the ductal system . With this technique, Lipid-soluble (e.g., Ethiodol) or non Lipid-soluble (e.g., Sinografi n) contrast solution is then slowly infused until the patient feels discomfort (usually between 0.2 and 1.5 ml).CONVENTIONAL SIALOGRAPHYThese iodine-containing agents render the ductal system radiopaque, The image of the ductal system appears as tree limbs, with no area of the gland devoid of ducts. With acinar filling, the tree comes into bloom, which is the typical appearance of the parenchymal opacification phase .

Non lipid-soluble contrast agents are preferred because of reports of inflammatory reactions subsequent to inadvertent extravasation of lipid-soluble agents .

Sialography is indicated for the evaluation of chronic inflammatory diseases and ductal pathoses. Contraindications include acute infection, known sensitivity to iodine-containing compounds, and immediately anticipated thyroid function tests.SialographyA, Lateral projection of the parotid demonstrating opacification all the way to the terminal ducts and acini. B, Anteroposterior projection of the same gland demonstrating parenchymal blushing from acinar opacifi cation.

Sialogram of Normal Submandibular Gland. This lateralview demonstrates parenchymal blushing. Normal fine branching isvisible. Lack of parenchymal blushing at the anteroinferior margin iscaused by radiographic burnout.

COMPUTED TOMOGRAPHYCT is useful in evaluating structures in and adjacent to salivary glands; it displays both soft and hard tissues and minute differences in soft tissue densities .CT is useful in assessing acute inflammatory processes and abscesses as well as cysts, mucoceles, and neoplasia. Calcifications such as sialoliths are also well depicted with CT.CT Images with Soft Tissue Algorithm. A, Axial viewdemonstrating bilateral enlargement of the parotid glands (arrowheads).B, Coronal view of the same patient. The clinical/histopathologicdiagnosis was autoimmune parotitis.

MAGNETIC RESONANCE IMAGINGMRI for soft tissue mass details and localization Differanciates :St vs. HtNormal vs. abnormal tissue Identifies facial nerve ( parotid )Containdications:-pacemaker-cochlear implant .These magnetic resonance images reveal a lymphoepithelial cyst involving the rightparotid gland. This axial T1-weighted image reveals a well-defined circular lesion involving the rightparotid gland with an internal signal isointense to muscle, and the matching T2-weighted image

reveals that the lesion has a high internal signal because of the fluid content

SCINTIGRAPHY (NUCLEAR MEDICINE, POSITRONEMISSION COMPUTED TOMOGRAPHY)Selective up take of techntiumAssesees silvary gland function (not anatomy)Expel technetium after stimulations

Scintigraphy. A, 99m Tc-pertechnetatescan of the salivary glands (right and left anterioroblique views) demonstrates increased uptake ofradioisotope in the right parotid gland (blackarrowhead). B, Scintigram taken after administrationof a sialogog (lemon juice) demonstratesretention of isotope in right parotid gland (whitearrowheads). This is a typical presentation of salivarystasis, Warthin tumor, or oncocytoma.

ULTRASONOGRAPHYFor superficial , soft tissue swillingDifferentioates cystic vs. solidUs-guide FNA

Ultrasonography (US) Image of Right Parotid Gland. Awell-delineated solid mass is suggested by echo returns within thelesion (arrows). US appearance is typical of a benign salivary tumor

Salivary gland disorders

Obstructive and inflammatory disordersSialolithiasisBacterial sialadenitisSialodochitisAutoimmune sialadenitis

sialolithiasis** calculus and salivary stones** Formation of calcified obstruction within salivary gland duct** Clinical features : Chronic retrograde infection Swelling and pain with eatingMajor or minor S.GUsually one S.G involvedSubmandibular S.G >> 83% of the cases

**Raiographic features :Radiopaque : * Vary from cigar to oval or round shape * Homogeneous radiopaque internal structureRadiolucent : ductal filling defect ** sialography is helpful when obstruction is undetectable on plain RG . ** CT may also detect minimally calcified sialoliths not visible on plain films.

A, This partial image of a standard mandibularocclusal fi lm reveals the presence of a sialolith(arrow). B, Sialograph of the same patient demonstratingfl ow of contrast past the stone (short arrows) anda negative fi lling defect (long arrow) from a smallerradiolucent sialolith. The proximal secondary ductswithin the gland show abnormal irregular wideningindicating sialodochitis.

36

Sialography should not be performed if a radiopaque stone has been shown by plain radiography to be in the distal portion of the duct More than 90% of stones larger than 2 mm are detected as echo-dense spots in US images D/D: phleboliths dystrophic calcification of LN palatine tonnsiliths

Tx: sialogogs to stimulate saliva secretion.Sialography may also stimulate discharge .Surgical removal of the sialolithRemoval of the whole involved S.G

40

41

42

FIG. 31-2 A, Stereoscopic panoramic plain fi lmprojection. Note the laminated appearance ofthis sialolith in the submandibular gland. Theimage of the sialolith is magnifi ed because of itsrelatively lingual placement in the image layer.Taken from slightly different horizontal angles, athree-dimensional appearance can be obtainedwhen viewed with stereobinoculars. B, Over-theshoulderocclusal projection revealing a sialolith.C, Anteroposterior skull view with cheek blownout to provide air contrast to reveal a parotidsialolith (arrow).43Bacterial sialadentisParotitis and sabmandibulitis

Acute or chronic bacterial infection of terminal acini or parenchyma of S.G Acute bacterial infections most commonly affect the parotid glandMost cases are unilateralmay occur at any ageClinical features : swelling redness Tenderness Malaise Enlarged regional lymph nodes suppuration may also be noted Untreated acute suppurative infections typically form abscesses.

Chronic bacterial infection : can affect any of major S.G causing extensive swelling and culminating in fibrosis may be a consequence of un-Tx acute sialadenitis or some types of obstruction . intermittent swelling, pain when eating, and superimposed infection resulting from salivary stasisRG features :Sialography is contraindicated in acute infectionsEpithelial flattening may lead to mildly dilated terminal ducts and saclike acini, which is demonstrable with sialography.even distribution throughout the gland is seen in recurrent parotitis and autoimmune disordersUS may distinguish between diffuse inflammation and suppurationMRI is an appropriate alternativeexamination in cases which sialography is contraindicatedTreatmentattention to oral hygiene local massageincreased fluid intake oral sialogogs (sour citrus fruit wedges or salivary stimulants).antibiotic regimen may also be indicated.surgical remedies ranging from partial to total excision of the gland

SialodochitisDuctal sialadenitisinflammation of the ductal system of the salivary glands.Clinical features : ** sialectasia or dilation of ductal system ** sausage-string appearance of the main duct and its major branchesTx : as tx of sialadenitis

Lateral view of a sialogram of a parotid gland demonstratinga negative fill defect (arrow) representing a noncalcified sialolithand prominent intermittent stricture and dilation of the main and secondaryducts, which is typical of advanced sialodochitis.Sausage string appearance of sialodochitis

Autoimmune SialadenitisMyoepithelial sialadenitis, Sjgren syndrome, benign lymphoepithelial Lesion Mikulicz disease , sicca syndrome, dacryosialoadenopathia atrophicans, and autoimmune sialosisgroup of disorders that affect the salivary glands and share an autosensitivityClinical features : ** range from recurrent painless swelling of the salivary glands (usually the parotid gland) to a stage that includes enlargement of the lacrimal glands ** xerostomia and xerophthalmiadiagnosis can be made on the basis of any two of the following three features: Dry mouth, dry eyes, and rheumatoid disease.most common in adults (40- 60 year-old )

90% to 95% female prevalence.

44 times greater risk for development of non-Hodgkin lymphoma

RG features :early stages : ** punctate and globular spheric collection of contrast agent throughout the G >>>> sialectases **main duct may appear normal, but the intraglandular ducts may be narrowed or not even evidentAs the disease progresses : ** the collections of contrast agent increase in size and are irregular in shape >> cavitary sialectases ** larger cavities of contrast agent and dilation of the main ductal system may also be present **Cavitation and glandular fibrosis are the result of recurrent inflammationAt the end point of this disorder, complete destruction of the gland occursD/D : chronic bacterial OR granulomatous infections multiple parotid cysts associated with (HIV) infection.Conventional Sialography of Left Parotid.Lateral projection demonstrates punctate sialectases distribute throughout the gland, which is suggestive of autoimmune sialadenitis. Clinical/histopathologic diagnosis was Sjgren syndrome

Anteroposterior projection ofthe same gland.Sialography of the Left Parotid.Punctate (small spheric), globular (larger spheric), and cavitary (larger, irregular) sialectases with some dilation of the main duct are suggestive of advanced autoimmune disease with parenchymal destruction with retrograde infection in lateral (A) and anteroposterior (B) projections. Clinical/histopathologic diagnosis was Sjgren syndrome

Tx :Relief of symptoms.Underlying systemic rheumatoid conditions are typically treated with anti-inflammatory agents, corticosteroids, and immunosuppressive therapeutic agents .Salivary stimulantsincreased fluid intakeartificial saliva and tearssurgically by local ortotal excision of the symptomatic gland.Non-inflammatory disorders 1- Sialadenosis 2- Cystic Lesions 3- Benign tumers : Benign Mixed Tumor Warthin Tumor Hemangioma 4- malignant tumers : Mucoepidermoid Carcinoma Malignant Mixed Tumor SialadenosisSialosisnonneoplastic, noninflammatory enlargement of primarily the parotid salivary glandsusually related to metabolic and secretory disorders of the parenchyma associated with diseases of nearly all the endocrine glands , protein deficiencies, malnutrition in alcoholics , vitamin deficiencies, and neurologic disordersEnlarged affected glands RG features : sialography>> may show enlarged (splayed duct) or normal S.G CT and MRI>> provide a more straightforward depiction of the glands but are nonspecific and require correlation with the clinical findings and history.Tx : identifying the cause of the metabolic or secretory disorderConservative tx : local massage increased fluid intake oral sialogogsSialadenosis34-year-old female with hypothyroidism. (a) Digital sialogram right parotid gland shows attenuated main duct and the intraparenchymal branches. (b) AxialT2weighted image demonstrates symmetrically enlarged parotid glands without any focal lesion

Cystic lesion:

cysts of the salivary gland are rare (less than 5% of all salivary gland mass)-most commonly occure unilaterally in parotid gland-they may be congenital(branchial),lymphoepithelial,dermoid or acqurid including mucous retention cysts-may be intraglandular or extraglandular

Cystic neoplasm-

Mucous extravationpseudo cysts : lack epithelial lining and result from ductal ruptureRanulas: are retention cysts usully occure as result of obstruction sublingual duct Benign lymphoepithelial cysts: sequelae of cystic degeneration of salivary inclusion within lymph nodesMulticentric parotid cysts associated with HIV

Radiographic features:

cystic lesion typically appear as well-circumscribed ,nonenhancing(with contrast)low density areas when examined on CTappear as well-circumscribed,high-signal areas on 2T-weighted MRI

Contwhen imaged with us,cysts are sharply marginated and echo free as dark area treatment : typically surgical , involving local or total excision of the gland

benign tumors

-relatively uncommon -occur in less than 0.003% of the population-3% of all tumors-80% of salivary tumors arise in the parotid -5% in the submandibular-1% sublingual-10%-15% minor salivary gland -most are bengine or low-grade malignancies-high-grade malignancies are uncommon

Contthe chance of neoplasm of major salivary glands being directly with the size of the gland

Radiographic features:-Benign tumors and low-grade malignancies may have a similar appearance-well-defined margins, which are most apparent on CT or MRI examinations-tumor to appear more radiopaque because the vascularity of the tumor is greater than that of the adjacent salivary gland tissue

cont-benign masses are typically less echogenic than parenchyma, sharply defined, and of essentially homogeneous echo strength and density-Sialography may suggest a space occupying mass when the ducts are compressed or smoothly displaced around the lesion (the ball-in-hand appearance)

Treatment typically surgicalthe parotid gland may be either partially or totally excisedsubmandibular and sublingual glands are in variably totally excised

Benign mixed tumor Pleomorphic adenomaa neoplasm arising from the ductal epithelium of major and minor salivary glands exhibiting epithelial and mesenchymal components.The benign mixed tumor accounts for 75% of all salivary gland tumorstypically occurs in the fifth decade of life as a slow-growing, unilateral, encapsulated, asymptomatic massA slight female predilection existsRecurrence occurs in 50% of cases after excisionMalignant transformation is reported in up to 15% of untreated cases

Radiographic feature:

sharply circumscribed in frequently lobulated and essentially round homogeneous lesion that has a higher density than the adjacent glandular tissueCalcifications within the tumor are commonly seen and are well depicted on CTThis tumor has various tissue signals in different MRI techniquesFoci of low signal intensity (dark areas) usually represent areas of fibrosis or dystrophic calcificationsIf a calcification is present (signal void) the diagnosis favors a benign mixed tumor

75CT and MRI Images of a( Pleomorphic Adenoma)In the T2-weighted image, note the increased signal of the tumor, which is now hyperintense to muscle.

contIn the axial MRI T1-weighted image, the tissue signal of the tumor is isointense with muscle

contIn the axial CT soft tissue algorithm image, note the well-defined periphery (black arrows). the internal density that is less than surrounding muscles. The remaining parotid gland (white arrow) is displaced laterally

Warthin tumor:

Papillary cystadenoma lymphomatosum, adenolymphoma, and lymphomatous adenomabenign tumor arising from proliferating salivary ducts trapped in lymph nodes during embryogenesis of the salivary gland79Clinical featuresthe second most common benign neoplasm of the salivary glandsaccounting for 2% to 6% of the parotid tumorslow-growing, painless, round-to-ovoid massIn 20% of cases the tumors are multipleTypically afflicts males older than 40 years and may be unilateral or bilateral Radiographic features:

CT and MRI are the preferred techniquesnot specific and istypical of benign salivary tumorsOn CT, this tumor may be of either soft tissue or cystic densityOn MRI, it is heterogeneous and may demonstrate hemorrhagic focicharacteristically intensely hot on 99m Tcpertechnetate scansThe US presentation of Warthin tumor is that of a solid mass (anechoic), if the massis not cystic

CONTAn axial soft tissue algorithm CT image of a case of bilateralWarthin tumor, a large tumor involving the left parotid (white arrow) and a much smaller tumor on the right side (black arrow)

Hemangioma:

Vascular nevusa benign neoplasm of proliferating endothelial cells (congenital hemangioma) and vascular malformations, including lesions resulting from abnormal vessel morphogenesis

Clinical features:

the most frequently occurring nonepithelial salivary neoplasm, accounting for 50% of the cases85% arise in the parotid glandthe most common salivary gland tumor during infancy and childhoodThe average age at diagnosis is 10 years.occurring in the first two decades of life 65%They are frequently unilateral and asymptomaticA 2:1 female-to-male predilection existsTreatment:

by local excision for those who do not undergo spontaneous remission

radiographic features:

Phleboliths are commonThey appear as discrete soft tissue calcifications with a radiolucent centerbest identified on plain films and CTThe CT presentation of hemangioma is a soft tissue mass that is well distinguished from surrounding tissueOn MRI the tumor has a signal similar to that of adjacent muscle onT1-weighted images and a very high signal on T2-weighted imagesUS usually demonstrates well-defined margins in the hemangiomaPhleboliths image as multiple hyperechoic areas within the body of the gland itself

Malignant tumor:

About 20% of tumors in the parotid are malignant50% to 60% of submandibular tumors90% of sublingual tumors60% to 75% of minor salivary gland tumors

Radiographic features:

variable and is related to the grade, aggressiveness, location, and type of tumorill-defined margins, invasion of adjacent soft tissues (such as fats paces), and destruction of adjacent osseous structures are considered to be typical indicators of malignancy

Treatment:

typically surgicalLow-grade malignant tumors of the parotid gland may be either partially or totally excisedSubmandibular and sublingual glands are invariably totally excisedHigh-grade tumors may require radical neck dissectionCombinations of surgery, the rapeutic radiation, and chemotherapy may also be used

Mucoepidermoid Carcinoma:

a malignant tumor composed of a variable admixture of epidermoid and mucous cells arising from the ductal epithelium of the salivary glands

90Clinical features :

the most common malignant salivary gland tumor (35%) most commonly the parotid gland.the rest are found in the minor glands, with the palatebeing the most frequent locationA wide age range exists, with the highest prevalence in the fifth decade of lifeA slight predilection for females existsThe low-grade variety rarely metastasizesmovable, slowly growing, painless noduleIt is usually only 1 to 4 cm in diameterThe prognosis is good; the 5-year survival rate is greater than 95%

CONT.high-grade tumors often cause facial pain and paralysis, have ill-defined margins and are relatively immobileMetastasis by blood and lymph are common with recurrence in half the patients after excisionThe prognosis is poor and varies with the histologic grade; the 5-year survival rate may be as low as 25%

Radiographic features:

low-grade mucoepidermoid carcinoma may present a lobulated or irregularly sharply circumscribed appearance on contrast enhanced CT or MRICystic are a may present and, rarely, calcifications may be seenhigh-grade mucoepidermoid carcinom atypically relies on the appearance of irregular margins and ill-defined form when the mass is examined with CT or MRIIn CT images, the tumor as an irregular homogeneous mass, slightly denser than the gland parenchyma

CONT ..high-grade mucoepidermoid carcinoma has homogeneous low signal intensity (dark) on T1-weighted images, but T2-weighted images are more heterogeneous and intense(brighter) than T1-weighted images but still slightly darker (low signal) relative to the surrounding tissuesCavitary sialectasia and ductal displacement may be noted on sialographic images of this tumor

Malignant Mixed Tumor:

Carcinoma ex mixed tumor, carcinoma ex pleomorphic adenoma and malignant pleomorphic adenomacomposed of three distinct types of tumorsThe most common is carcinoma ex mixed tumor which arises from the epithelial components of a preexisting benign mixed tumor

CONT .The other two, which are extremely rare :1-true malignant mixed tumor (from both epithelial and mesenchymal components of a mixed tumor)2-the metastasizing mixed tumor, which appears histologically benign but behaves in a malignant fashion

These four axial CT and magnetic resonance images depict an adenoid cystic carcinoma of the right submandibular gland. Notethe well-defined periphery, making it difficult to differentiate from a benign tumor The internal density of the tumor in this soft tissue algorithmCT image is almost equal to the remaining gland

CONT..The tissue signal in this T1-weighted magnetic resonance image is very slightly less than the remaining gland

a T2-weighted magnetic resonance image, the high signal of the tumor contrasts with the remaining gland

a T1-weighted postgadolinium, fat-saturation image, the tumor has a higher signal than in the remaining gland

CONT.

Clinical features:

typically begins as a slowly growing mass that suddenly undergoes rapid proliferationoften accompanied by pain and facial paralysisMetastasis is early and the prognosis is unfavorable

Radiographic features:

The presentation of this tumor is similar to that of the high-grade mucoepidermoid carcinomaMRI is usually superior to CT for tumor definitionOTHER MALIGNANT AND METASTATIC TUMORSAlthough the incidence of other malignant tumors of the major salivary glands is low, a significant variety exists in their histogenesisOf all malignant salivary gland tumors, 23% are adenoid cystic carcinomasthe majority of these neoplasms develop in the minor salivary glandsAdenocarcinoma accounts for 6.4% of all salivary gland malignancieswith acinic cell carcinoma, primary lymphoma, and squamous cell carcinoma occurring with even less frequency

CONT.cell carcinoma occurring with even less frequencyPain, paresthesia and even paralysis may be present, especially in high-grade tumorsTumor spread may be by direct invasion or metastasisMetastasis of tumors of the salivary glands is not unusualMetastatic lesions in the parotid gland are more commonMost metastatic lesions of the parotid gland occur through the lymphatic system and include squamous cell carcinoma, lymphoma, and melanomametastasis from the lung, breast, kidney, and gastrointestinal tract has been reported Radiographic features:

nonspecific and similar to that of the high-grade mucoepidermoid carcinomaUS may demonstrate echo-free cystic areas in adenoid cystic carcinomas.

CONT .This axial soft tissue algorithm CT image reveals an adenocarcinoma of the left parotid gland.

Almost all the gland has been replaced by this ill-defined tumor that has some peripheral enhancement .

and lower density internal structure, likely representing necrotic regions

CONT.Ultrasonography. The mass in the submandibular gland(arrows) demonstrates a heterogeneous hypoechoic pattern compared with the adjacent tissue. The histopathologic diagnosis was adenoid cystic carcinoma

CONT.Contrast-enhanced axial soft tissue algorithm CT imagedemonstrating a mass in right parotid gland with a poorly marginated.heterogeneous, slightly lobulated appearance (white arrows).Poorly defined margins suggest a low-grade malignancy rather than benign tumor , although the CT appearance of both is similar . Histopathologic diagnosis was low-grade mucoepidermoid carcinoma

CONT.