1494 • Rarely parathyroid adenomas present as a palpable mass. • Radiology: m Several imaging methods have been used for localization of hyperfunctioning parathyroid tissue, including retrograde phlebotomy for determination of serum parathormone levels, CT scanning, ultrasonography, magnetic resonance imaging (MRI), thallium subtraction scanning, and technetium-99m sestamibi imaging. m Technetium-99m sestamibi imaging appears to be the most useful, with localization of more than 90% of adenomas, and has been most widely used in patients with anatomic distortion due to previous surgery and in patient who are high surgical risks; however, more routine utilization has gained support. m Multidimensional CT (referred to as 4D-CT) emerging technique used in detection when a lesion is not identified by more conventional tech- niques (e.g., ultrasonography, sestamibi imaging) • May be associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT): m Autosomal-dominant disorder with germline mutation in HRPT-2 gene on chromosome 1q25-31 m Characterized by: – Parathyroid adenoma or carcinoma – Fibro-osseous lesions of the jaw (e.g., ossifying fibroma of mandible or maxilla): 30% of cases – Renal cyst, hamartoma, carcinoma: 20% of cases m Approximately 80% of patients develop hyperparathyroidism: – Usually presents late in adolescence – Hypercalcemia tends to be severe. m Higher incidence of parathyroid carcinoma in comparison with patients with MEN-1 and MEN-2A m Renal lesions may include: – Renal cysts, polycystic renal disease, renal hamartoma – Papillary renal cell carcinoma, renal cortical adenomas, Wilms tumor • 90% of adenomas are found in parathyroid glands in their usual locations: m Lower glands are more commonly involved. Chapter Neoplasms of the Parathyroid Glands CLASSIFICATION OF NEOPLASMS OF THE PARATHYROID GLANDS (Box 33-1) 33 BOX 33-1 Neoplasms of the Parathyroid Glands • Parathyroid adenoma • Parathyroid carcinoma • Secondary neoplasms PARATHYROID ADENOMA (Figs. 33-1 through 33-22, Table 33-1) Definition: Benign neoplasm of the parathyroid paren- chymal cells, including chief cells and/or oncocytic cells. Clinical • More common in females (F : M = 3 to 4:1); occur over a broad age range but are most frequently dis- covered in the fourth and fifth decades. • Represents the major cause of primary hyperparathyroidism • Clinical findings are essentially the same as those associated with primary hyperparathyroidism due to hyperplasia (see Chapter 32). • As in primary hyperparathyroidism due to hyperpla- sia, the symptomatology in patients with parathy- roid adenomas is changing as a result of routine biochemical screening and early detection: m Hypercalcemia may be incidentally discovered in asymptomatic patients, and many patients com- plain only of fatigue, weakness, or depression. m Nephrolithiasis is documented in 69% of men and in 36% of women with adenomas overall, but the incidence has been decreasing in recent years to between 5% and 20%. m Severe bone disease, once a common complica- tion, is now rare; however, osteopenia is often present, and joint disease similar to that found in patients with parathyroid hyperplasia occurs. • Serum calcium levels are generally higher than in patients with primary chief cell hyperplasia but not usually as high as in parathyroid carcinoma. • Hypophosphatemia, hyperphosphaturia, and ele- vated serum parathormone levels are found. ISBN: 978-1-4557-3382-8; PII: B978-1-4557-3382-8.00034-7; Author: Wenig; 00034 ISBN: 978-1-4557-3382-8; PII: B978-1-4557-3382-8.00034-7; Author: Wenig; 00034 b0010 p0015 u0015 u0020 c00034 s0010 p0010 s0015 p0035 s0025 p0040 u0030 u0035 u0040 u0045 u0050 u0055 u0060 u0065 u0070 u0075 u0080 u0085 u0090 u0095 u0100 u0105 u0110 u0115 u0120 u0125 u0130 u0135 u0140 u0145 u0150 u0155 u0160 u0165 Wenig_Chapter 33_main.indd 1494 4/29/2015 5:28:36 PM To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter Toppan Best-set. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication.
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• Radiology:m Several imaging methods have been used for
localization of hyperfunctioning parathyroidtissue, including retrograde phlebotomy fordeterminationofserumparathormonelevels,CTscanning, ultrasonography, magnetic resonanceimaging (MRI), thallium subtraction scanning,andtechnetium-99msestamibiimaging.
m Technetium-99msestamibiimagingappearstobethemost useful,with localizationofmore than90% of adenomas, and has been most widelyusedinpatientswithanatomicdistortionduetoprevious surgery and in patient who are highsurgical risks;however,more routineutilizationhasgainedsupport.
m Multidimensional CT (referred to as 4D-CT)emerging technique used in detection when alesionisnotidentifiedbymoreconventionaltech-niques(e.g.,ultrasonography,sestamibiimaging)
• May be associated with hyperparathyroidism-jawtumorsyndrome(HPT-JT):m Autosomal-dominant disorder with germline
mutation in HRPT-2 gene on chromosome1q25-31
m Characterizedby:– Parathyroidadenomaorcarcinoma– Fibro-osseouslesionsofthejaw(e.g.,ossifying
fibromaofmandibleormaxilla):30%ofcases– Renal cyst, hamartoma, carcinoma: 20% of
• Represents the major cause of primaryhyperparathyroidism
• Clinical findings are essentially the same as thoseassociatedwithprimaryhyperparathyroidismduetohyperplasia(seeChapter32).
• Asinprimaryhyperparathyroidismduetohyperpla-sia, the symptomatology in patients with parathy-roid adenomas is changing as a result of routinebiochemicalscreeningandearlydetection:m Hypercalcemiamaybeincidentallydiscoveredin
m Nephrolithiasis is documented in 69% of menand in 36% of women with adenomas overall,but the incidence has been decreasing in recentyearstobetween5%and20%.
m Severe bone disease, once a common complica-tion, is now rare; however, osteopenia is oftenpresent,andjointdiseasesimilartothatfoundinpatientswithparathyroidhyperplasiaoccurs.
• Serum calcium levels are generally higher than inpatientswithprimarychiefcellhyperplasiabutnotusuallyashighasinparathyroidcarcinoma.
• Hypophosphatemia, hyperphosphaturia, and ele-vatedserumparathormonelevelsarefound.
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1495
Fig. 33-1.Classic parathyroid adenoma identified on ultrasonography.
A,Sagittalultrasonographicimageshowsahypoechoic,well-definedmass(A)justbelowtheinferiorpoleoftherightthyroidgland(*).B,TransverseultrasonographicimagewithcolorflowDopplershowstheincreasedperipheralarchofvascularityofthemassfrequentlyseenwithadenomas(A).(From Som PM, Curtin HD: Head and neck imaging, ed 5, Philadelphia, 2011, Elsevier, Fig. 41-95, p 2663.)
m Ectopicadenomas,especiallyintrathyroidalones,maybemissedbyclinicalevaluationand/orsurgi-calexploration:– Intrathyroidal parathyroid adenomas may be
misinterpreted by pathologic evaluation as athyroid follicular lesion or medullary thyroidcarcinoma.
m Reportsofadenomasoccurringinsupernumeraryglands include tumors arising in the vagusnerve, pericardium, or other soft tissue sites intheneck.
PathologyCytology• Occasionally enlarged parathyroid glands, either
hyperplastic or, more commonly, adenomatous,have been serendipitously subjected to fine-needleaspirationasaclinicallysuspected“solitarythyroidnodule”;reportsofultrasonicallyguidedfine-needleaspirationforlocalizationandconfirmationofpara-thyroidproliferativediseasehaveappeared.
• Anawarenessofthetypicalcytologicappearanceofparathyroidtissuecanbehelpfulduringintraopera-tiveexaminationofbiopsiesduringaneckexplora-tion for hyperparathyroidism, as examination oftouchpreparationsprovidesa rapidmeansofcon-firmingthepresenceofparathyroidtissue.
• Aspirates of parathyroid tissue typically containnumerous naked nuclei, as well as small sheets ofcells, sometimes forming acinar or follicular struc-tures;smallaggregatesofdensecolloid-likematerialmaybeseenbutarenotnumerous.
• The cells are generally small, with predominantlyround nuclei; anisonucleosis in scattered cells andoccasionallarge,atypical,nakednucleiarecommon.
• Thecytoplasmisgranularandmayexhibitscatteredlarge metachromatic granules with a May-Grünwald-Giemsa or Romanowsky stain;Papanicolaou-stainedcellshavecleartofinelygranu-larcytoplasm.
• The distinction from follicular epithelium of thethyroidmaybedifficult,althoughthecellsareusuallysmallerthanthoseofthethyroid:m Immunohistochemical staining for PTH, parafi-
• A remnant of uninvolved parathyroid tissue at theperipheryofthetumormaybevisible.
• Cystic change may be present, and when markedmaymasktheneoplasticnatureoftheproliferation;markedcysticdegeneration is frequentlyassociatedwithscarringandcalcification.
• There is significant variation in weight, with mostbetween0.3and1.0g.
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1496 SECTION 9 ParathyroidGlands
Fig. 33-2.Parathyroid adenoma.
Parathyroidadenomadetectedby201Tl/99mTc-pertechnetatesubtractionimaging(AtoC)andby99mTc-sestamibisubtractionimagingwith123I(D).A,99mTc-pertechnetateconcentratedwithinthethyroidgland.B,201Tlconcentratedwithinthyroidandparathyroidglands.C,Computertechniquesallowtechnetiumconcentratedinthethyroidglandtobesubtractedfromthalliumthataccumulateswithinthyroidandparathyroidtissue.Afterthyroidsubtraction,aparathyroidadenomaisnotedasafocusofincreasedthalliumuptake(arrows).D,99mTc-sestamibisubtractionimagingwith123Ishowsanadenomabelowtheinferiorpoleoftheleftlobeofthethyroidgland.(From Som PM, Curtin HD: Head and neck imaging, ed 5, Philadelphia, 2011, Elsevier, Fig. 41-103, p 2669.)
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1497
B
*
A
C
D
Fig. 33-3.4D-CT in the detection of a small adenoma.
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F,Coronalmaximumintensityprojectionimageinanteriorprojectionshowstheadenoma(arrow).G,Coronalmaximumintensityprojectionimageintheposteriorprojectionshowstheadenoma(*)posteriortothecommoncarotidartery.(Cases courtesy of Dr. Lawrence Ginsberg. From Som PM, Curtin HD: Head and neck imaging, ed 5, Philadelphia, 2011, Elsevier, Fig. 41-101, p 2667.)
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1499
m Nuclei of residual normal or atrophic parathy-roidglandtypicallysmallerthanthenucleioftheadenoma.
• Growthpatternsincludesolid(diffuse)sheets,cords,nests,acini,follicles,andmicrocysts:m Follicle formation may contain eosinophilic
basal location within the cell and have incon-spicuous nucleoli; usually lack significantpleomorphism:– Cells with hyperchromatic enlarged nuclei as
well as multinucleated cells are common andcanbe found scattered throughout the tumoror may be clustered in small foci; these scat-tered atypical nuclei are not an indicator ofmalignancy in the absence of other evidenceof a malignancy (see section on parathyroidcarcinoma).
m Cytoplasmvaries,includingslightlyeosinophilic,amphophilic,clear,oroxyphilic.
m Chiefcellsofanadenomafrequentlylargerthanthe non-neoplastic chief cells in the uninvolvedrimofparathyroidtissue,ifoneispresent
m Oncocyticcellsmaybeseeninvariablenumbers,focally admixed with chief cells or as nodularaggregates.
• Mitotic figures are identifiable in many adenomas,butusuallynumberfewerthan1per10high-powerfields;mitoticratesashighas4mitosesper10high-powerfieldshavebeendescribedinoccasionalcases.
• Delicate vascular network composed of thin fibro-vascularstroma,sinusoid-likebloodvesselsorcapil-lariestraversetheneoplasm.
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thandothecellsintheuninvolved(orsuppressed)parathyroidtissue,eitherinotherglandsorinarim of non-neoplastic parathyroid tissue in anadenomatousgland.
• Cells with markedly enlarged and hyperchromaticpleomorphic or bizarre-appearing nuclei may bepresentandwhenpresent:m Appearadmixedwithbland-appearingnuclei.m Tendtobefocallyandnotdiffuselyidentified.m Occurintheabsenceofincreasedmitoticactivity
• Reactiveanddegenerativechangesmaybepresent,including cyst formation, edema, fibrosis, hemor-rhage (freshor in the formofhemosiderindeposi-tion),orinfarction:m Mayoccurspontaneouslyormayoccurfollowing
a traumatic event such as prior surgery to theneckorfine-needleaspirationbiopsy
m Presence of reactive and degenerative changes,especiallyfibrosis,maycauseadherencetoadja-centstructures,suggestinginvasivegrowthandapossiblediagnosisofparathyroidcarcinoma.
m Infarctedtumormayretainantigenicityforpara-thyroidhormone.
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m Fat stains, when used with adequate clinicalinformation, intraoperative findings, and histo-logicexamination,areuseful if their limitationsarekeptinmind.
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1504 SECTION 9 ParathyroidGlands
m Distinction between hyperplasia and adenomamay be extremely difficult and requires thepathologic examination of more than a singlegland.
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Fig. 33-20.Parathyroid adenoma associated with osteitis fibrosa cystica.
Left panel,Theadenomaistypicalwithadistinctcapsuleandarimofnormalparathyroidparenchymaincludingmaturefat(lower);right panel,thetumoriscomposedofchiefcells.Thepatienthadapathologicfractureofthehumerusaswellasgeneralizedosteopeniawithmultiplelyticskeletallesions.Atthetimeofpresentationhehadhypercalcemia.Theinitialclinicalimpressionwasmetastaticcarcinomawithsecondaryhypercalcemia.
Histologic Variants of Parathyroid Adenoma• Oncocytic(oxyphilic)adenoma(seeFig.33-18):
m Exclusively composed of oncocytic cells withprominenteosinophilicgranularcytoplasm
m Demographicfeaturesaresimilartothoseofthemorecommonadenomascomposedofchiefcells
m Thoughttobenonfunctional;usuallyassociatedwith lesser degree of hypercalcemia; however,several reports document an association withprimaryhyperparathyroidism
m Composed of large cells with abundant eosino-philic granular cytoplasm and hyperchromaticnuclei:– Scattered large atypical nuclei or multinucle-
atedcellsmaybeseen.– Cytoplasm is stuffed with mitochondria on
m Intrathyroidallocalizationmaysuggestadiagno-sis of an oncocytic thyroid follicular (so-calledHürthlecell)neoplasm:– Parathyroid oncocytic adenomas have more
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1506 SECTION 9 ParathyroidGlands
m Circumscriptionand/orencapsulationaswellaslarge size (1 to 15cm) support adenomatousnature:– May be associated with a compressed rim of
“normal”glandm May be difficult to recognize as “abnormal”
parathyroid tissue in small biopsies, when theyareeasilymistakenfornormalparathyroidtissuebecauseoftheabundanceofstromalfat
m Stromal fat often contains areas of fibrosis ormyxoidalteration.
m Mostareassociatedwithhyperparathyroidism.• Otherrarevariantsofparathyroidadenomainclude:
m Papillary variant characterized by prominentpapillaryarchitecture:– May not be a “true” variant but papillary
architecture, especially in association withfibrosis and hemorrhage (recent and remote),likelyisareactive/degenerativephenomenon
m Follicular variant characterized by prominentfollicular(acinar)architecture
m Water-clearvariantcharacterizedbypresenceofpolygonalcellswithclearcytoplasmanddistinctcellmembranes.
• Atypicalparathyroidadenoma:m Definition: parathyroid tumor showing features
worrisomeforparathyroidcarcinomabutlackingabsolute diagnostic features for parathyroidcarcinoma
m Synonymsincludeatypicalparathyroidneoplasm,parathyroidneoplasmof uncertain biologic sig-nificance, or parathyroid neoplasm inconclusiveformalignancy
m Atypicalhistologicfeaturessuggestingcarcinomabutfallingshortforthisdiagnosismayinclude:– Capsular irregularities or invasion without
infiltrationintoadjacentsofttissues– Increased mitotic activity (>5 per 10 high-
powerfields)– Intralesional fibrosis characterized by broad
fibrousbandscoursingthroughthelesion– Coagulativenecrosis– Diffusecellularatypia– Diffuse sheet-like growth of monotonous
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1507
TABLE 33-1 Comparative Features of Parathyroid Proliferative Diseases
Hyperplasia Adenoma Carcinoma
Gender; age Slight female predilection; most common in 5th-6th decades
More common in women; most common in 4th decade
Equal gender predilection; wide age range
Clinical Asymptomatic or complaints of lethargy, weakness, polyuria, polydipsia, arthralgia, constipation, and depression
Similar to hyperplasia Similar to hyperparathyroidism of benign cause but more severe due to the higher serum calcium levels; higher proportion of renal disease (nephrolithiasis) and bone disease; peptic ulcer disease; palpable neck mass more common than in adenoma
Serum calcium 11.7 mg/dl (average) 12.5-13.5 mg/dl Often >14 mg/dl
Intraoperative findings
2 or more glands enlarged, easily dissected; enlargement may be very asymmetric
1 gland enlarged; easily dissected; more frequent in lower glands or ectopic sites
1 gland enlarged; often adherent to surrounding tissues
Weight Total gland weight usually <1 g, but may be up to 5 g
0.3-1.0 g commonly, but may weigh several grams in patients with bone disease
>1.5 g (often much larger)
Capsule Circumscribed by capsule of parathyroid gland, may be incomplete. No compressed rim of atrophic or normal parathyroid tissue
Thin tumor capsule, often surrounded by rim of uninvolved parathyroid, which may appear atrophic
Thickened capsule; rim of normal parathyroid rarely seen
Gross appearance Gray-brown, soft. Cut surface may be homogeneous or nodular. Lacks fibrous bands
Red-brown, firm. Usually homogeneous, lacks fibrous bands
Gray-white, firm, often lobulated or irregular. Fibrous bands often produce coarse nodularity
Histologic pattern Diffuse or nodular, sometimes pseudofollicular or acinar
Diffuse or nodular, frequently pseudofollicular or acinar
Diffuse, nodular, pseudofollicular, or acinar; often trabecular pattern with distinctive nuclear palisading predominates
Cytologic features Chief cells predominate; transitional and oncocytic cells often present
Chief cells predominate, but mixture of chief, transitional, and oncocytic cells may be seen; rarely, purely oncocytic
Cells usually resemble chief cells, but variable cytoplasmic oncocytic change may be seen; cell borders often indistinct
Intracytoplasmic lipid
Decreased Decreased in tumor; abundant in atrophic rim of parathyroid
Usually absent
Stromal fat cells Scanty to absent Usually absent in tumor; present rim of atrophic parathyroid
Absent
Nuclear morphology Normal to slightly increased N-to-C ratio; usually without nuclear pleomorphism
Nuclei enlarged, with variability in size; scattered groups of large pleomorphic, hyperchromatic nuclei, or multinucleated cells
Increased N-to-C ratio; enlarged atypical nuclei; often with monotonous (bland appearing) nuclei
Nucleoli Inconspicuous to small Inconspicuous to small Frequently prominent and enlarged
Mitoses Common (60% of cases; most with <1 mitotic figure/10 HPF)
Common (70% of cases; most with <1 mitotic figure/10 HPF)
Common (80% of cases), may include atypical mitoses; may be numerous
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1508 SECTION 9 ParathyroidGlands
Hyperplasia Adenoma Carcinoma
Capsular and vascular invasion
Absent Absent; entrapment of tumor cells may occur in capsule if degenerative changes present
Capsular invasion present in two thirds; may involve only capsule or extend into adjacent tissues
Vascular invasion present in up to 15%; usually in capsular vessels
Remainder of gland Entire gland is abnormal Normal or atrophic Normal
Degenerative changes
May be seen in very large glands
Includes hemorrhage, areas of fibrosis, and cystic change
Common, especially in larger adenomas; includes hemorrhage, fibrosis, and cystic change, sometimes calcification
Tumor cell necrosis; calcification and cystic changes may be present
Treatment Subtotal parathyroidectomy with surgical removal of three glands, leaving a remnant of the 4th or total parathyroidectomy* with autotransplantation of parathyroid tissue in forearm
Surgical removal of the enlarged gland
En bloc resection, including ipsilateral thyroid lobe and adjacent soft tissues
Prognosis Excellent Excellent Up to 50% of patients are cured by en bloc resection; considered an indolent malignancy even in presence of recurrence or metastasis with long survival even after recognition of tumor recurrence; morbidity and mortality correlate to complications of severe hypercalcemia
Recurrence and metastasis
Recurrence in approximately 16% of cases due to inadequate neck exploration and may not be evident for years
Absent Recurrence in two thirds of patients usually within 3 years of the first surgery; metastasis is 35%, is a late event usually preceded by local recurrence; most commonly to lung, cervical lymph nodes, and liver
Familial and/or MEN association
Yes, in approximately 20% of cases
Uncommon Rare
TABLE 33-1 Comparative Features of Parathyroid Proliferative Diseases—cont’d
g, Grams; HPF, high power fields; MEN, multiple endocrine neoplasia syndrome; N-to-C, nuclear-to-cytoplasmic.*Particularly in cases of familial hyperparathyroidism.
m Mostatypicalparathyroidadenomasprovetobebenigninlong-termfollow-up,butowingtotheuncertainty in their malignant potential, theyhavebeentermedatypical.
m Treatment is similar to a typical parathyroidadenoma, but patients should be followed forpotential recurrent hyperparathyroidism, localrecurrence of tumor, and/or evidence of aggres-sivebehavior(e.g.,metastasis).
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1509
• Some favor a full bilateral neck exploration withsubtotal parathyroidectomy and have reported alower incidence of recurrent hypercalcemia thatrequiredreoperation:m There isanincreasedincidenceofpostoperative
hypoparathyroidismwiththisprocedure.• Recurrence rates vary significantly and may reflect
problems in classification, particularly in cases ofhyperplasiawithnodules,whichmayerroneouslybedesignatedasadenomas.
• Although generalized osteopenia is now morecommon, osteitis fibrosa cystica, also known asbrowntumorofhyperparathyroidismisoccasionallyseen(seeFigs.33-20to33-22):m Mayoccurinhyperparathyroidismofanycause
but is related to degree and duration of serumcalciumelevation
m Lesionsarecharacterizedbyresorptionofbone,whichisreplacedbyfibroustissue,probablyasareparativeresponsetomicrofractures
m Hemorrhagewithinthefibroustissueleadstotheaccumulationofhemosiderinandaproliferationof multinucleated giant cells in addition to theosteoclasts
m With timedegenerative changes lead to the for-mationofcysticspaces
m Osteitis fibrosa cystica cannot be distinguishedhistologically from the giant cell (reparative)granuloma of the jaw; clinical information isessential.
• Recurrent hyperparathyroidism following surgeryfor an adenoma may also result from incompleteexcision,ruptureofthetumorcapsulewithspillageinto the operative field, or from hyperfunction ofautografted parathyroid tissue following subtotalparathyroidectomy.
PARATHYROID CARCINOMA (Figs. 33-23 through 33-38, see Table 33-1)
secretion and are similar to those in patients withhyperparathyroidismofbenigncausebuttendtobemoresevereduetothehigherserumcalciumlevels:m Presenting symptoms include polyuria, polydip-
sia,fatigueandweakness,depression,bonepainand fracture (high incidence in earlier series),renalcolicandnephrolithiasis(uptotwothirdsofpatientsinearlierstudies,butprobablydecreas-ingwithroutinebiochemicalscreeningandearlierdetection), peptic ulcer disease, and recurrentpancreatitis.
genemayplayanimportantroleinthedevelop-mentofparathyroidcarcinoma,and itsabsencemay be helpful in distinguishing parathyroidadenomafromcarcinoma.
m Some cases occur in hyperparathyroidism-jawtumor syndrome, MEN, or familial isolatedhyperparathyroidism.
m Externalbeamirradiationtotheneckmaybeapossibleriskfactor.
m Rare cases occur in patients with secondaryhyperparathyroidism,possiblylinkingthedevel-opmentofparathyroidcarcinomafromparathy-roidadenomaorhyperplasia.
• May be associated with hyperparathyroidism-jawtumorsyndrome(HPT-JT):m Autosomal-dominant disorder with germline
mutation in HRPT-2 gene on chromosome1q25-31
m Characterizedby:– Parathyroidadenomaorcarcinoma– Fibro-osseouslesionsofthejaw(e.g.,ossifying
fibromaofmandibleormaxilla):30%ofcases
BOX 33-2 Clinical Features Associated with Malignancy in Parathyroid Neoplasms
• Serum calcium level >14 mg/dl• Serum parathormone levels 2 to 3 times normal• Severe metabolic manifestations: nephrolithiasis, bone
disease, etc.• Palpable neck mass• Difficulty in surgical dissection owing to adherence to
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1510 SECTION 9 ParathyroidGlands
Fig. 33-23.Parathyroid carcinoma in a patient with severe hyperparathyroidism.
A,AxialT2-weightedMRimageshowsademarcated2.5-cmmediastinalmass(*)thatrepresentsaparathyroidcarcinoma.B,AxialT2-weightedMRimageofanotherpatientwithhypercalcemiashowsanonhomogeneousmassintherighttracheoesophagealgroove.Themarginsareslightlyunsharp.Thisisaparathyroidcarcinoma.C,AxialT2-weightedMRimageshowsalargemassintherighttracheoesophagealgrooveinthispatientwithseverehypercalcemia.Atsurgery,thiswasaparathyroidcarcinoma.(From Som PM, Curtin HD: Head and neck imaging, ed 5, Philadelphia, 2011, Elsevier, Fig. 41-110, p 2674.)
A
*
B
C
– Renal cyst, hamartoma, carcinoma: 20% ofcases
– Approximately 80% of patients develophyperparathyroidism.
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Parathyroidcarcinomaappearingasanirregular,infiltrative,indurated,whiteneoplasmadherenttotheadjacentthyroidlobe(on the left).Difficultiesindissectionaparathyroidlesionfromadjacentstructuresissuggestive,althoughnotdefinitivelydiagnostic,forcarcinoma.Histologicconfirmationisalwaysrequiredforadiagnosisofparathyroidcarcinoma.
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1514 SECTION 9 ParathyroidGlands
• Nuclearpleomorphismislesscommonthaninade-nomas, which often contain scattered foci withenlargedatypicalnuclei:m Monotonyofnuclearsizeandshapeisfrequently
presentincarcinomas.m Pleomorphism, when present, is usually more
diffusethaninadenomas.• Mitotic activity is identified in most, but not all,
the presence of mitotic activity exceeding 1 per10high-powerfieldsinaminorityofparathyroidadenomasandinparathyroidhyperplasiamaybeseen.
m Overlap inmitoticactivitybetweenallparathy-roidproliferativediseases (i.e.,adenoma,hyper-plasia, and carcinoma) makes mitotic activity ausefulfindingonlywhencoupledwithotherfea-turesofmalignancy.
• Capsularinvasionmaybeobviousinsomecases,ormay be represented only by irregular tongues orislands of parathyroid tissue protruding into thecapsule;invasionbeyondthecapsuleisindicativeofmalignancy:m Entrapped islands of parathyroid parenchymal
cells in benign disease should be distinguishedfrom these invasive foci by their rounded con-toursandlackofdesmoplasticreaction.
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CHAPTER 33 NeoplasmsoftheParathyroidGlands 1515
• Fibrous bands extending from a thickened capsulefrequentlydividethetumorintoirregularcompart-mentsand/ornodules.
• Angioinvasion is diagnostic of carcinoma but ispresentinaminorityofcases:m Usually foundwithinvessels in the thick tumor
capsulem Artifactually displaced clumpsof tumor cells in
vascularspacesshouldbedistinguishedfromtrueinvasionbytheirfrequentlydegeneratedappear-ance and by their lack of attachment to thevesselwall.
ofparathyroidcarcinoma– Loss of immunoreactivity for Rb protein
reported in 20% to 100% of parathyroidcarcinomas
– Absencemaybehelpfulindistinguishingpara-thyroid adenomas from carcinomas but notconsidered sufficiently reliable in differentiat-ingadenomafromcarcinoma
m SomaticmutationinMEN-1gene:– Foundin13%ofcarcinomas– Suggests a role in the development of
carcinomam Alleliclossofthep53m Reduced expression of cyclin-dependent kinase
inhibitorproteinp27commonlyidentified:– In contrast, adenomas show higher labeling
m Represents microscopic foci of hyperplasticparathyroid tissue in the soft tissues of theneck in association with primary chief cellhyperplasia
m May be the cause of recurrent disease after anapparently complete resection of the grosslyevidenthyperplasticglands
m Should not be mistaken for invasion as seen inparathyroid carcinoma; differentiating featuresmayinclude:– Absence of associated fibroblastic reaction or
infiltrativecontour– Absence of an intravascular location of these
nests– Absence of other histologic features of carci-
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1516 SECTION 9 ParathyroidGlands
m StageI:invasionofsurroundingsofttissues;90%disease-freesurvival
m Stage II: vascular invasion; 46% disease-freesurvival
m Stage III: invasion of vital organs or regionallymphnodemetastasis;50%disease-freesurvival
m Stage IV: distant metastases; no disease-freesurvival
SECONDARY NEOPLASMS (Fig. 33-39)
Definition: Contiguous involvement from tumors inadjacentstructuresormetastaticneoplasmsfromdistantsitesinvolvingtheparathyroidgland.
Clinical• Usually asymptomatic; may present with a neck
• May result from direct extension, especially fromthyroid or laryngeal tumors, or from metastaticspread
• Metastasis to parathyroid glands is rare; amongthe more common primary malignancies that maymetastasizetotheparathyroidglandsinclude:m Breastcarcinoma(mostcommon)m Hematologicmalignancies
Treatment and Prognosis• Surgeryistheprimarytreatmentmodalitywithrec-
ommendedtreatmentincludingenblocresection,toinclude the ipsilateral thyroid lobe, strap muscles,recurrent laryngeal nerve, trachea, or esophagus ifinvolved:m Offersthebestchanceforcurem Up to 50% of patients are cured by en bloc
resection.• Prophylactic lymphadenectomy not recommended
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