Diagnostic Cytopathology Volume 19 Issue 6 1998 [Doi...

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Fine-Needle Aspiration of the Mediastinum: A Clinical, Radiologic, Cytologic, and Histologic Study of 42 Cases Nina S. Shabb, M.D., 1 * Mehieddine Fahl, M.D., 2 Basem Shabb, M.D., 3 Patrecia Haswani, M.D., 1 and Ghazi Zaatari, M.D. 1 Forty-two fine-needle aspirates (FNA) of the mediastinum were reviewed from 1984–1995. The clinical, radiologic, pathologic, and cytologic material was studied. Twenty-five males and 17 females had an age range from 10–72 yr and a mean of 41 yr. Common complaints were chest pain, dyspnea, and cough. Thirty- eight tumors were in the anterior/superior mediastinum. Fifty- seven percent were primary neoplasms (Hodgkin’s lymphoma, 7; non-Hodgkin’s lymphoma, 6; thymoma, 3; germ-cell tumor, 3; thymic carcinoid and angiosarcoma, 1 each; and malignant not otherwise specified, 3). Twenty-four percent were metastatic tu- mors (carcinoma, 9; and sarcoma, 1). Twelve percent were benign conditions (granulomatous disease, 2; multinodular goiter, 1; extramedullary hematopoesis, 1; and one thymic cyst). Seven percent were inconclusive. FNA yielded adequate tissue for diagno- sis in 83% and a correct diagnosis in 86%. There was one false-negative and no false-positive diagnosis. FNA is a useful tool for accurate tissue diagnosis of mediastinal masses. Diagn. Cytopathol. 1998;19:428–436. r 1998 Wiley-Liss, Inc. Key words: aspiration biopsy; mediastinum; lymphoma; thymoma The mediastinum is defined as the space between the pleura laterally and limited by the sternum anteriorly, the vertebral column posteriorly, the sternal notch superiorly, and the diaphragm inferiorly. It is the site of a myriad of nonneoplas- tic and neoplastic conditions both benign and malignant, primary and metastatic, many of which present as mediasti- nal masses. Although the clinical data, the location in the mediastinum, and the radiologic findings all help in narrow- ing the differential diagnosis, a tissue diagnosis is very helpful in proper guidance of management prior to definitive treatment of these varied diseases. The role of fine-needle aspiration (FNA) in the mediastinum has been controversial due to the complexity and difficulty of diagnosing these cases even on surgical biopsy material, and also due to the danger incurred by the proximity of the heart and great vessels. 1–19 We reviewed our experience with FNA of the mediastinum to assess its role in this setting. Materials and Methods All cases of FNA of the mediastinum were retrieved by reviewing the cytology, radiology, and tumor registry files at the American University of Beirut Medical Center from January 1984–October 1996. Patients’ charts were reviewed and the clinical and demographic data were recorded. All available radiologic studies were reviewed. Tumor size and characteristics were recorded. The FNA cytology slides and the surgical pathology slides were reviewed first by one pathologist and then together with a second pathologist in a blind fashion. All the aspirates except two were performed by an interventional radiologist under CT or ultrasound guidance. In 2 patients, the masses were in the superior mediastinum and readily palpable. In these cases, the pathologist performed the aspirate. Three to five passes per lesion were performed. Cytologic material was immediately smeared onto glass slides and air-dried for staining with Diff-Quik (Harleco, Gibbstown, NJ) or fixed in Carnoy’s solution (9:1 70% ethanol:glacial acetic acid) for staining with the Papanicolaou stain. In some cases the needle and syringe were rinsed in saline solution for cell-block prepara- tion. The surgical specimens were formalin-fixed, routinely processed, and stained with hematoxylin-eosin. In a few cases, immunohistochemical stains were performed on the cell blocks or the surgical specimens when indicated. Results We had a total of 42 patients with an age range from 10–72 yr and a mean of 41 yr (Table I). There were 25 males and 17 1 Department of Pathology, American University of Beirut, Beirut, Lebanon 2 Department of Radiology, American University of Beirut, Beirut, Lebanon 3 Department of Surgery, American University of Beirut, Beirut, Lebanon *Correspondence to: Nina S. Shabb, M.D., Department of Pathology, American University of Beirut, 850 Third Avenue, New York, NY 10022. E-mail: [email protected] Received 27 December 1997; Accepted 3 June 1998 428 Diagnostic Cytopathology, Vol 19, No 6 r 1998 WILEY-LISS, INC.

description

Diagnostic Cytopathology Volume 19 Issue 6 1998 [Doi 10.1002_(Sici)1097-0339(199812)19!6!428__aid-Dc5_3.0.Co;2-f] Nina S. Shabb; Mehieddine Fahl; Basem Shabb; Patrecia Haswani; G

Transcript of Diagnostic Cytopathology Volume 19 Issue 6 1998 [Doi...

Page 1: Diagnostic Cytopathology Volume 19 Issue 6 1998 [Doi 10.1002_(Sici)1097-0339(199812)19!6!428__aid-Dc5_3.0.Co;2-f] Nina S. Shabb; Mehieddine Fahl; Basem Shabb; Patrecia Haswani; G

Fine-Needle Aspiration of theMediastinum:A Clinical, Radiologic, Cytologic,and Histologic Study of 42 CasesNina S. Shabb, M.D.,1* Mehieddine Fahl, M.D.,2 Basem Shabb, M.D.,3

Patrecia Haswani, M.D.,1 and Ghazi Zaatari, M.D.1

Forty-two fine-needle aspirates (FNA) of the mediastinum werereviewed from 1984–1995. The clinical, radiologic, pathologic,and cytologic material was studied. Twenty-five males and 17females had an age range from 10–72 yr and a mean of 41 yr.Common complaints were chest pain, dyspnea, and cough. Thirty-eight tumors were in the anterior/superior mediastinum. Fifty-seven percent were primary neoplasms (Hodgkin’s lymphoma, 7;non-Hodgkin’s lymphoma, 6; thymoma, 3; germ-cell tumor, 3;thymic carcinoid and angiosarcoma, 1 each; and malignant nototherwise specified, 3). Twenty-four percent were metastatic tu-mors (carcinoma, 9; and sarcoma, 1). Twelve percent were benignconditions (granulomatous disease, 2; multinodular goiter, 1;extramedullary hematopoesis, 1; and one thymic cyst). Sevenpercent were inconclusive. FNA yielded adequate tissue for diagno-sis in 83% and a correct diagnosis in 86%. There was onefalse-negative and no false-positive diagnosis. FNA is a useful toolfor accurate tissue diagnosis of mediastinal masses.Diagn.Cytopathol. 1998;19:428–436.r 1998 Wiley-Liss, Inc.

Key words:aspiration biopsy; mediastinum; lymphoma; thymoma

The mediastinum is defined as the space between the pleuralaterally and limited by the sternum anteriorly, the vertebralcolumn posteriorly, the sternal notch superiorly, and thediaphragm inferiorly. It is the site of a myriad of nonneoplas-tic and neoplastic conditions both benign and malignant,primary and metastatic, many of which present as mediasti-nal masses. Although the clinical data, the location in themediastinum, and the radiologic findings all help in narrow-ing the differential diagnosis, a tissue diagnosis is veryhelpful in proper guidance of management prior to definitive

treatment of these varied diseases. The role of fine-needleaspiration (FNA) in the mediastinum has been controversialdue to the complexity and difficulty of diagnosing thesecases even on surgical biopsy material, and also due to thedanger incurred by the proximity of the heart and greatvessels.1–19 We reviewed our experience with FNA of themediastinum to assess its role in this setting.

Materials and MethodsAll cases of FNA of the mediastinum were retrieved byreviewing the cytology, radiology, and tumor registry files atthe American University of Beirut Medical Center fromJanuary 1984–October 1996. Patients’ charts were reviewedand the clinical and demographic data were recorded. Allavailable radiologic studies were reviewed. Tumor size andcharacteristics were recorded. The FNA cytology slides andthe surgical pathology slides were reviewed first by onepathologist and then together with a second pathologist in ablind fashion. All the aspirates except two were performedby an interventional radiologist under CT or ultrasoundguidance. In 2 patients, the masses were in the superiormediastinum and readily palpable. In these cases, thepathologist performed the aspirate. Three to five passes perlesion were performed. Cytologic material was immediatelysmeared onto glass slides and air-dried for staining withDiff-Quik (Harleco, Gibbstown, NJ) or fixed in Carnoy’ssolution (9:1 70% ethanol:glacial acetic acid) for stainingwith the Papanicolaou stain. In some cases the needle andsyringe were rinsed in saline solution for cell-block prepara-tion. The surgical specimens were formalin-fixed, routinelyprocessed, and stained with hematoxylin-eosin. In a fewcases, immunohistochemical stains were performed on thecell blocks or the surgical specimens when indicated.

ResultsWe had a total of 42 patients with an age range from 10–72yr and a mean of 41 yr (Table I). There were 25 males and 17

1Department of Pathology, American University of Beirut, Beirut,Lebanon

2Department of Radiology, American University of Beirut, Beirut,Lebanon

3Department of Surgery, American University of Beirut, Beirut, Lebanon*Correspondence to: Nina S. Shabb, M.D., Department of Pathology,

American University of Beirut, 850 Third Avenue, New York, NY 10022.E-mail: [email protected]

Received 27 December 1997; Accepted 3 June 1998

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Table I. Demographic, Clinical, Cytologic, and Pathologic Data: FNA of Mediastinal Lesionsa

Diseasecategories

Ageandsex Symptoms

Location andcharacteristics

of tumorSize(cm)

FNAdiagnosis

Pathologydiagnosis

Surgicalprocedure Comments

LymphomaHodgkin’s

1 22 F Dyspnea andcough

Ant. Solid, well-circumscribed

10 C/W Hodgkin’s Hodgkin’s NS Suprasternalmediastinotomy

2 55 M None, routineCXR

Ant. 8 C/W Hodgkin’s 1. Nondiagnostic2. Hodgkin’s NS

Both: mediasti-notomy

First mediasti-notomy; nondi-agnostic

3 32 F Dyspnea andcough

Ant. Solid,invading chestwall

8 C/W Hodgkin’s Hodgkin’s NS Mediastinotomy

4 27 F Dyspnea andcough

Ant./superior,solid

8 C/W Hodgkin’s Hodgkin’s NS Cervical LNbiopsy

FNA done withoutX-ray guidance

5 16 M Chest pain Ant. Solid,invading chestwall

8 C/W Hodgkin’s Hodgkin’s NS Mediastinotomy

6 38 M Chest pain Ant. Multiple,invading chestwall

4 S/O thymoma 1. Nondiagnostic2. Hodgkin’s NS

Both: mediasti-notomy

FNA misdiag-nosed as S/Othymoma

7 31 F Chest pain Ant. Multiple,invading chestwall

5 Nondiagnostic Hodgkin’s NS Mediastinotomy

Non-Hodgkin’s,LCL

8 56 F Chest mass Ant. Solid,invading chestwall

8 LCL LCL, diffuse Cervical LN bx

9 30 M Dyspnea Ant. Invadingchest wall

6 LCL No bx None Treated on FNAresult; surgeryavoided

10 17 M Shoulder pain Ant. Solid 8 LCL No bx None11 25 F Dyspnea and

coughAnt. Solid Large 1. Malignant NOS

2. Nondiagnostic1. Hodgkin’s NS2. LCL

Both: mediasti-notomy

Non-Hodgkin’s,lympho-blastic

12 13 M Cough Ant. Solid Large Lymphoblasticlymphoma

No bx None Treated on FNAresult; surgeryavoided

13 10 M Cough Ant. Solid 15 Lymphoblasticlymphoma

No bx None Treated on FNAresult; surgeryavoided

Thymoma14 30 M Chest pain Ant. Solid and

cystic7 Thymoma Thymoma, nonin-

vasiveMedianster-

notomySurgical biopsy

avoided15 51 M SVC syndrome

dyplopiaAnt./Superior,

solid7 Thymoma Thymoma, inva-

siveMedianster-

notomySurgical biopsy

avoided16 60 M None, routine

CXRAnt. Solid 2.5 Thymoma Thymoma, non-

invasiveMedianster-

notomySurgical biopsy

avoidedGerm-cell tumor

17 34 M Chest pain Ant. Solid,invading chestwall

5 Undifferentiatedtumor, GCT?

GCT, embryonaland yolk sac

Mediastinotomy Multiple lungnodules

18 24 M Cough Ant. Solid andcystic

Large Undifferentiatedtumor, GCT?

GCT, embryonaland choriocar-cinoma

Mediastinotomy High serummarkers

19 25 M Cough Ant. Solid andcystic

7 C/W GCT No bx None Multiple lungnodules, highserum markers

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Table I. (continued)

Diseasecategories

Ageandsex Symptoms

Location andcharacteristics

of tumorSize(cm)

FNAdiagnosis

Pathologydiagnosis

Surgicalprocedure Comments

Thymic carcinoid20 58 F Chest pain and

dyspneaAnt. Solid and

cystic10 Nondiagnostic,

scantyThymic carcinoid

(atypical)Mediastinotomy

Angiosarcoma21 43 M Dyspnea and

hemoptysisAnt. Solid and

cystic12 Spindle-cell neo-

plasmAngiosarcoma Mediastinotomy Multiple lung

nodulesMalignant neo-

plasmNOS

22 50 F None, routineCXR

Ant. Solid andcystic

Large Malignant NOS Undifferentiatedcarcinoma

Thoracotomy,biopsy

Cytokeratin1,PLAP &HCG2

23 35 M Intercapsularpain

Post. Solid 8 Malignant NOS Malignant NOS Thoracotomy,biopsy

Cytokeratin, LCA,PLAP, HCG2

24 35 M Cough Ant. Solid Large Malignant NOS,favor lym-phoma

Malignant, favorlymphoma

LFU Cytokeratin,PLAP, alphaFP2, LCA1?

Metastatic tumorsOat cell

25 50 M Cough Ant. ? Ca/lymphoma No bx None Revised FNAreading: oat-cell ca

26 65 F Cough Ant. Solid Large Oat cell No bx None27 47 F Not available Ant. ? Ca/lymphoma No bx None Revised FNA

reading: oat-cell ca

Adenocarci-noma

28 57 M Chest pain Ant. Solid 7 Adenocarcinoma No bx None29 32 F None, routine

CXRAnt. Solid 5 Adeno C/W breast No bx None History of breast

ca30 56 M Cough and

hemoptisisAnt. Solid Large Adenocarcinoma No bx None

Poorly differen-tiatednonoat cell

31 56 M Dyspnea andchest pain

Ant. Solid 10 Ca/lymphoma P.D. carcinoma,nonoat cell

Thoracoscopy 2-cm lung mass.Revised FNAreading: PD ca

32 50 M Dysphagia Post. Solid Large Ca/lymphoma Metastatic ca toLN

Mediastinoscopy History of LCL 12yr prior.Revised FNAreading: PD ca

33 51 M Not available Ant. Solid Large P.D. carcinoma,nonsmall cell

No bx None Lung mass

Small round-cell sar-coma

34 21 M Dyspnea Ant./superior,solid

5 Metastatic smallround-cell sar-coma

No bx None History of smallround-cell sar-coma of flank, 9mo prior

Benign conditionsGranulomatous

disease35 20 M Cough, shortness

of breathAnt. Cystic 2.5 Necrosis and a

few giant cellsGranulomas,

tuberculosisMediastinotomy

36 40 F Cough Ant. Cystic Large Granulomas Noncaseatinggranulomas,sarcoid

Mediastinotomy FU c/w sarcoid

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females. The most common symptoms were dyspnea, cough,and chest pain. Six patients were asymptomatic from theirmediastinal lesion and were discovered by routine chestX-rays. Thirty-eight of the aspirated tumors were in theanterior or anterior/superior mediastinum, while only fourwere in the posterior mediastinum. Tumor size ranged from2.5–15 cm, with a mean of 7.5 cm. The majority of thetumors were solid, some were mixed solid and cystic, and afew cases were purely cystic. Seven tumors had invaded thechest wall (mostly lymphomas and one germ-cell tumor).

The majority of cases (57%) were primary neoplasms ofthe mediastinum (Table II). The second largest category wasof metastatic neoplasms (24%), mostly carcinomas. Benignconditions accounted for 12%, while inconclusive casesaccounted for 7%.

Overall Performance of FNAThe fine-needle aspirate yielded adequate tissue for diagno-sis in 35 of 42 cases (83%) (Table III). In 7 cases theaspirates were scanty and hence inadequate for diagnosis.This was related to dense fibrosis in the lesion in 2 cases oflymphoma, and to extensive necrosis in one case of tubercu-losis. In 4 cases the cause of the inadequate specimen wasnot evident but may have been related to poor cooperation ofthe patient, or poor aspirating technique.

Twenty-two patients (52%) had surgical interventioneither in the form of a limited surgical biopsy for diagnosticpurposes or a procedure such as thoracotomy or medianster-notomy for excision of the lesion. When compared to thesurgical pathology results when available, or compared to

the final diagnosis reached by review of the FNA by thepathologists in this study along with the clinical outcome,the fine-needle aspirate was correctly diagnosed in 30 of the35 cases with adequate cytology (86%). One case wasmisdiagnosed: a case of Hodgkin’s lymphoma was calledsuggestive of thymoma on FNA. Four cases were underdiag-nosed: all of these were metastatic carcinomas to themediastinum where the FNAs were read as malignantneoplasm, carcinoma vs. lymphoma.

Table I. (continued)

Diseasecategories

Ageandsex Symptoms

Location andcharacteristics

of tumorSize(cm)

FNAdiagnosis

Pathologydiagnosis

Surgicalprocedure Comments

Multinodulargoiter

37 62 F Dysphagia Post. Solid 3 Multinodulargoiter

No bx None Iodine uptake con-firmed thyroid

originExtramedullary

hemato-poeisis

38 39 F None, routineCXR

Post. Solid 3 Extramedullaryhematopoeisis

No bx None History of con-genital dyser-ythropoeticanemia

Thymic cyst39 58 F None, routine

CXRAnt. Unilocular

cystLarge 50 cc fluid, c/w

thymic cystNo bx None

Inconclusive40 60 F Dyspnea Ant. Solid Large Nondiagnostic LFU None41 72 M Not available Ant. ? Nondiagnostic LFU None42 65 F Not available Ant. ? Nondiagnostic LFU None

aAnt., anterior; bx, biopsy; C/W, consistent with; Ca, cancer; CXR, chest X-ray; GCT, germ-cell tumor; LCL, large-cell lymphoma; LFU, lost to follow-up;LN, lymph node; NOS, not otherwise specified; NS, nodular sclerosis; P.D., poorly differentiated; Post, posterior; S/O, suggestive of; SVC, superior venacava.

Table II. Mediastinal Masses Divided According to Disease Categorya

Disease category No. of cases Percent

Primary neoplasms 24 57Lymphoma 13Thymoma 3GCT 3Thymic carcinoid 1Angiosarcoma 1Malignant NOS 3

Metastatic neoplasms 10 24Carcinomas 9Sarcoma 1

Benign conditions 5 12Granulomas 2MNG 1EMH 1Thymic cyst 1

Inconclusive 3 7Total 42 100

aGCT, germ-cell tumor; NOS, not otherwise specified; MNG, multinodulargoiter; EMH, extramedullary hematopoisis.

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There was one false-negative diagnosis where a Hodgkin’slymphoma was misdiagnosed as a thymoma; there was nofalse-positive diagnosis.

Only one complication was documented in the clinicalcharts, which was a pneumothorax necessitating chest tubeinsertion and a 2-day hospital stay.

The common and interesting lesions will be discussed,while the rare lesions are described in Tables I–III.

Primary NeoplasmsLymphoma

Hodgkin’s lymphoma.There were 7 cases of Hodgkin’slymphoma (HL). The mean age was younger than thatof the group, i.e., 31 yr compared to 41 yr. There were 4females and 3 males. All the tumors were solid, and4 had invaded the anterior chest wall. FNA was consistentwith Hodgkin’s disease in 5 of the 7 cases where Reed-Sternberg cells, a few classic ones but mostly variants,were seen in a background of a mixture of inflammatorycells; mature lymphocytes, a few eosinophils, plasmacells, and histiocytes (Fig. 1). In case 6, the FNA wasmisinterpreted as suggestive of thymoma. Review of theslides showed that in reality the tumor was not sampled,but the aspirate consisted of sheets of mesothelial cells,a few groups of bronchial epithelial cells, and clusters ofhistiocytes, along with scattered lymphocytes. The overallcellularity was moderate to scant. The sheets of meso-thelial cells, along with the clustered histiocytes, weremisinterpreted as the epithelial component of a thymoma(Fig. 2).

A limited surgical biopsy in the form of a mediastinotomywas performed in all 7 cases. In one case where the FNA was

consistent with HD, the first mediastinotomy was nondiag-nostic, yielding only fibrous tissue, fat, and a mixture ofinflammatory cells. The second mediastinotomy yieldeddiagnostic material.

In all 7 cases the surgical biopsies revealed nodularsclerosis HD.

Non-Hodgkin’s lymphoma.There were 6 cases of non-Hodgkin’s lymphoma (NHL), 4 of large-cell lymphoma(LCL), and 2 of lymphoblastic lymphoma (LL). The meanage was younger than that of the group: 25 yr compared to41 yr. The 2 patients with lymphoblastic lymphoma wereage 10 and 13 yr. There were 4 males and 2 females. Alltumors were solid, and two had invaded the anterior chestwall. The FNA was consistent with NHL in 5 of the 6 caseswith proper subclassification. The aspirates were cellular,showing mostly discohesive lymphoid cells with lymphoglan-dular bodies in the background. In the LCL cases the cellswere predominantly large with irregular nuclei, with or

Table III. Overall Performance of FNAa

Disease categoryand no. of cases Adequate Inadequate Correct Incorrect

Primary neoplasmsHodgkin’s, 7 6 1 5 1Non-Hodgkin’s, 6 5 1 5 0Thymoma, 3 3 0 3 0GCT, 3 3 0 3 0Thymic carcinoid, 1 0 1Angiosarcoma, 1 1 0 1 0Malignant NOS 3 0 3 0

Metastatic neoplasmsCarcinoma, 9 9 0 5 4b

Sarcoma, 1 1 0 1 0Benign conditions

Granulomas, 2 1 1 1 0MNG, 1 1 0 1 0EMH, 1 1 0 1 0Thymic cyst, 1 1 0 1 0

Inconclusive, 3 0 3Total, 42 35 7 30 5

aGCT, germ-cell tumor; MNG, multinodular goiter; EMH, extramedullaryhematopoiesis.bThese cases were initially diagnosed as carcinoma vs. lymphoma.

Fig. 1. Hodgkin’s lymphoma. A classic Reed-Sternberg (RS) cell (arrow)seen in a mixed inflammatory background (Papanicolaou stain,3400).Inset: RS variant.

Fig. 2. Sheets of histiocytes intermixed with a few lymphocytes, misinter-preted as thymoma (Papanicolaou stain,3400).

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without nucleoli. In the cases of LL, the cells were interme-diate in size with irregular nuclear contours, and bland,even chromatin without conspicuous nucleoli (Fig. 3).Mitotic figures and tingible body macrophages were alsoseen. Immunophenotyping of these lymphomas was notdone.

Three patients were treated on the bases of the FNAresults. Two patients underwent surgical biopsy, confirmingthe FNA diagnosis in both cases. One patient was lost tofollow-up.

ThymomaThere were 3 cases of thymoma. All were adult males with amean age of 47 yr. One patient had symptoms of myastheniagravis. Two tumors were solid, and one was solid and cystic.The FNAs of all 3 cases were consistent with thymoma. Thesmears were biphasic and composed of epithelial cells andlymphocytes (Fig. 4). The epithelial cells were in large,cohesive, mostly two-dimensional fragments, with somesmaller fragments and rare single cells. The cells hadabundant cytoplasm which was poorly defined. The nucleiwere round to oval, and occasionally spindled, and wereregular and small with bland chromatin. They were evenlyspaced within the fragments and did not overlap. Anaplasiaand mitosis were absent. The number of lymphocytesintermingled with these epithelial fragments varied fromarea to area in the same case and from case to case. Thelymphocytes were abundant and either lay on top of theepithelial fragments or were scattered throughout the slide.The lymphocytes were small and round, and appearedmature. No other elements were seen.

A limited surgical biopsy was avoided in all 3 cases, andthe surgeon went directly to mediansternotomy and excisionof the tumor. In one case, however, the thymoma wasinvasive and deemed inoperable; only a biopsy was taken.

The surgical specimens showed thymoma in all 3 cases (typeI in 2 cases and type II in one case).

Germ-Cell TumorsThere were 3 cases of germ-cell tumors (GCT). All were inadult males with a mean age of 28 yr. Two of the tumorswere mixed solid and cystic, while the other was purelysolid. In addition to the mediastinal masses, 2 patients hadmultiple lung nodules. Serum markers (alpha-fetoproteinand HCG) were elevated in 2 patients. FNA showed ahigh-grade epithelial-type neoplasm in all 3 cases, which inconjunction with the serum markers and the young age of thepatients made the diagnosis of GCT most likely on FNA(Fig. 5). In one case, syncytiotrophoblasts were seen on theFNA slide.

One patient was treated on the basis of the FNA. Twopatients had a limited surgical biopsy. In these cases thebiopsy showed mixed, nonseminomatous GCT.

Fig. 3. Lymphoblastic lymphoma. Discohesive lymphoid cells of interme-diate size with bland, even chromatin and convoluted nuclear contours.Lymphoglandular bodies are evident (arrowhead) (Papanicolaou stain,3400).

Fig. 4. Thymoma. Biphasic lesion composed of round to oval and spindledepithelial cells, intermixed with mature lymphocytes (Papanicolaou stain,3400).

Fig. 5. Germ-cell tumor. High-grade epithelial-type tumor cells (Papanico-laou stain,3400).

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AngiosarcomaThis patient presented with a mixed solid and cystic anteriormediastinum mass with multiple lung nodules. FNA showeda monotonous population of spindle cells. The cells were indensely cellular fragments composed of a single populationof monomorphic hyperchromatic spindle cells which lackedcytologic atypia, pleomorphism, and mitotic figures. Thediagnosis was spindle-cell neoplasm; differential diagnosesincluded spindle-cell thymoma (although a lymphoid compo-nent was lacking) and monomorphic sarcoma. Mediasti-notomy and biopsy revealed an angiosarcoma. The tumorcells were positive for factor VIII.

Malignant Neoplasms, Not Otherwise SpecifiedThere were 3 cases in this category where the FNAs and thesurgical biopsies showed an undifferentiated malignantneoplasm. Two of the patients were young adult males.Immunohistochemical markers for germ-cell tumors werenegative in all three. Cytokeratin was positive in one,favoring a poorly differentiated carcinoma of undeterminedorigin, while LCA was weakly positive in another, favoringa lymphoma. Two patients were lost to follow-up immedi-ately after the biopsies, and the third patient had dissemi-nated malignancy in his abdomen and chest while onchemotherapy and passed away 2 mo after diagnosis.

Metastatic NeoplasmsThere were 9 metastatic carcinomas and one metastaticsarcoma.

Six cases were of lung primary. In these cases themediastinal mass was so large as to obscure the origin fromthe lung, or the mediastinal mass was dominant with a smallmass in the lung. FNA in 3 cases were small-cell undifferen-tiated (oat-cell) carcinoma, 2 were poorly differentiatednonsmall-cell carcinoma, and one was adenocarcinoma.

One metastatic adenocarcinoma was from a breast pri-mary. In 2 cases, the primary lesion was unknown. Theoriginal reading on four of these FNAs was malignantneoplasm, carcinoma vs. lymphoma. Review of these aspi-rates revealed features of carcinoma in all four.

Benign ConditionsGranulomatous DiseaseThere were 2 cases in this category. The first (case 35) was a20-yr-old man who had by radiologic and clinical impres-sion an aggressive invasive lesion in the anterior mediasti-num. FNA yielded necrotic material and a few giant cells. Atsurgical exploration the lesion was found to be poorlycircumscribed, with invasive margins. Frozen section re-vealed caseating granulomas. Tissue culture later grewMycobacterium tuberculosis. The second case (case 36) wasa 40-yr-old woman who had enlarged anterior mediastinallymph nodes. FNAshowed well-formed, noncaseating granu-

lomas with giant cells (Fig. 6). A limited surgical biopsyrevealed noncaseating granulomas. Stains for tuberculosisand fungi were negative. Cultures were also negative. Adiagnosis of sarcoidosis was favored.

Multinodular GoiterThis 62-yr-old woman (case 37) presented with dysphagia.Her past medical history was significant for partial thyroid-ectomy 10 yr prior to her presentation. A CT scan showed awell-defined solid mass in the posterior mediastinum, 3 cmin size. FNA showed many large open sheets of follicularepithelium in honeycombed arrangement, with smaller col-loid-containing follicles, a few histiocytes, and colloidmaterial in the background (Fig. 7). Further radiologicstudies showed a thin band of tissue connecting this mass tothe anterior neck. Iodine uptake studies were positive,proving the true thyroid nature of the lesion.

Fig. 6. Noncaseating granuloma. An aggregate of epithelioid histiocytes(left), a giant cell (arrow), and mature lymphocytes (Papanicolaou stain,3400).

Fig. 7. Multinodular goiter. A sheet of follicular thyroid epithelium in ahoneycombed pattern (Papanicolaou stain,3400).

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Extramedullary HematopoesisThis 39-yr-old woman, already diagnosed with congenitaldyserythropoetic anemia, presented with complaints relatedto severe anemia. In addition to low hematocrit and heartfailure, she had a well-defined, solid, 3-cm mass in theparavertebral area in the posterior mediastinum. FNA re-vealed a mixture of hematopoetic elements, including manymegakaryocytes, granulocytes, and erythrocytes (Fig. 8). Adiagnosis of extramedullary hematopoeisis was made, andthe patient was saved a surgical procedure.

Thymic CystIn this case, the FNA yielded 50 cc of clear fluid. The cystdisappeared after the aspirate. The FNA in this case was bothdiagnostic and therapeutic.

DiscussionAlthough the role of FNA in the mediastinum remainscontroversial,1–4,6,8,9our results have shown that despite thecystic, necrotic, and fibrotic nature of many of these lesions,the tissue adequacy by FNA was remarkably good (83%),and that despite the varied pathologic entities and thedifficulty in reaching a correct diagnosis even in opensurgical biopsies, our diagnostic accuracy by FNA was 86%.

The patient demographics in this study are similar to thosein previously reported series,1,4,14 with a wide age range(10–72 yr) and a male predominance (60%).

In contrast to similar previously reported data,1,4 our studyhad a predominance of primary mediastinal lesions (57%),while metastatic tumors accounted for only 24%. Othersimilar reports have a predominance of metastatic tumors intheir series. This discrepancy is explained by our studydesign. The aim of the study was to assess the dignosticaccuracy of FNA in ‘‘primary’’ mediastinal lesions; hence,

those cases that were obviously metastatic to the mediasti-num were not included.

Many reports in the literature attest to the difficulty indiagnosing and accurately distinguishing between thymo-mas and lymphomas by FNA alone, and recommend the useof core-needle biopsy in these cases.2,4,8,15In our study, thesecases were readily diagnosed by FNA alone. Ten of the 13lymphomas and all 3 of the thymomas were correctlydiagnosed. Hodgkin’s disease of the mediastinum is usuallyof the nodular sclerosis subtype, where dense fibrosis mayinterfere with good cellular yield, and the paucity of classicReed-Sternberg cells may make the diagnosis by FNAdifficult. Despite the above-mentioned difficulties, 5 of the 7cases of Hodgkin’s lymphoma yielded good cellularity, andthe diagnosis was suspected not on finding classic Reed-Sternberg cells, but on finding Reed-Sternberg variants inthe appropriate cellular background of inflammatory cells.As is well-known, a definitive diagnosis of HL should not bemade on FNA alone. Confirmation needs to be obtained bysurgical biopsy. The advantage of FNA in these cases is thatthe surgeon would know that he or she is dealing with alymphoma and can plan for a limited surgical procedure.

Non-Hodgkin’s lymphoma of the mediastinum is mostoften diffuse large-cell or lymphoblastic.19,20 Smears areusually cellular and composed of dispersed single cells withlymphoglandular bodies in the background. The distinctionbetween the two subtypes is made on the cytologic details ofthe cells, taking into account cell size, nuclear contours,shape, and chromatin pattern. Tingible body macrophagesand many mitotic figures are seen more often in high-gradelymphoblastic lymphoma.20

In this study, all cases of thymoma had the classicbiphasic pattern of bland epithelial cells in a background ofmature lymphocytes, and hence did not raise diagnosticdifficulties. This may not always be the case, since spindle-cell thymomas and heavily lymphocytic thymomas mayindeed be problematic by FNA. In this study, one case (aHodgkin’s lymphoma) was incorrectly suspected of being athymoma. The aspirate was scanty and was not representa-tive. Sheets of benign mesothelial cells and aggregates ofhistiocytes were misinterpreted as the epithelial componentof a thymoma, while a few lymphocytes were interpreted asthe lymphocytic component. Similar difficulties have beenreported in the literature.1 The diagnosis of thymoma shouldonly be made when there is adequate cellularity in additionto the typical biphasic pattern.

The distinction between poorly differentiated carcinomaand lymphoma was not made in 4 of our cases. These werecalled malignant neoplasms, lymphoma vs. carcinoma.These cases were from the early part of the study, where thelimited expertise and confidence of the pathologist may haveplayed a role. Review of these cases showed typical cellclustering, nuclear molding, nuclear variability, and hyper-chromasia typical of carcinoma. The absence of lymphoglan-

Fig. 8. Extramedullary hematopoeisis. Two megakaryocytes in a back-ground of erythroid and granulocytic precursors (Papanicolaou stain,3400).

FNA OF THE MEDIASTINUM

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dular bodies was also a helpful feature. In difficult cases theuse of immunohistochemical markers may help in resolvingthe issue. Small-cell carcinoma is distinguished from nons-mall-cell carcinoma by the small size of the cells, minimal toabsent cytoplasm, evenly hyperchromatic nuclei, absence ofprominent nucleoli, and nuclear molding.

When the FNA yields undifferentiated malignant cells,particularly in young adult males, then the diagnosis ofgerm-cell tumor needs to be seriously considered. Materialfor cell-block and immuhistochemical stains should beobtained in addition to serum markers. Elevated serummarkers in conjunction with undifferentiated malignant cellson FNA in this setting may be adequate to diagnosegerm-cell tumor. In some cases, despite surgical biopsy anda battery of immunohistochemical stains, a definite subclas-sification of the neoplasm cannot be achieved.

Although benign conditions are reported to be difficult todiagnose by FNA,14–164 of the 5 cases in this study yieldedgood cellularity and accurate diagnosis. Two of these cases(a nodule of goiter extending to the posterior mediastinumand a mass of extramedullary hematopoeisis also in theposterior medistinum) were accurately diagnosed by FNA,avoiding surgical intervention.

We conclude that FNA is a good diagnostic tool in lesionsof the mediastinum, as a first attempt at tissue diagnosis. Itmay result in a definitive diagnosis avoiding surgicalintervention, such as in some cases of non-Hodgkin’slymphoma, GCTs, or metastatic tumors. If a definitivediagnosis cannot be reached, then a preliminary diagnosiswould help to guide the surgeon in his or her surgicalapproach. Nonsurgical conditions (such as lymphomas andGCTs) could be approached with a mediastinotomy andlimited surgical biopsy, while surgical diseases such asthymomas would be approached with a thoracotomy ormediansternotomy for total surgical removal of the lesion.

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