Embed Size (px)
Citation preview
HEPATIC UNDIFFERENTIATED (EMBRYONAL) SARCOMA: A CASE REPORT WITH FINE NEEDLE ASPIRATION CYTOLOGY AND HISTOLOGY
Fang Fan, MD, PhD, Ossama Tawfik, MD, PhD, and Paramjit Bhatia. M D 0 Center, Kansas City, Kansas , USA
Department o f Pathology and Laboratory Medicine, University of Kansas M e d i c a l
Kyo Rak Lee, MD, Kansas City, Kansas , USA
0 Department o fRadio logy , University o f K a n s a s Medical Center,
Jameson Forster, M D, 0 M e d i c a l Center, Kansas City, Kansas , USA
SurgerylLiver Transplant U n i t , University o f Kansas
Hepatic undzfferentiated (embryonal) sarcoma is an unusual malignant liver tumor with an over- whelming predilection f o r children. Fine needle aspiration (FNA) cytologr of these tumors rarely has been described in the literature. In this report, we described the clinical, radiologic, cytomorphologic, histopathologic, immunohistochemical, and DNA ploidy features of a similar tumor in an 18year-old patient. The FNA smears showed clusters and isolated tumor cells with marked variation in morphology including spindle cells, large bizarre anaplastic cells, and giant tumor cells. T h e histopathologic sections recapitulated the varied morphologic patterns within the tumor cells and also showed characteristic eosinophilic intra- and extracytoplasmic globules. DNA ploidy studies, ly image analysis, demonstrated this tumor as an aneuploid tumor, indicating poor Frognosis. FNA cytologr can be utilized as a sensitive screening tool for these rare tumors.
Keywords embryonal sarcoma, liver, undzfferentiated sarcoma
Hepatic undifferentiated (embryonal) sarcoma (UES) is a rare malignant liver tumor. It was reported initially as a malignant mesenchymoma by Stanley et al. [l] and later as UES by Stocker and Ishak in 1978 based on review of 31 cases [2]. More than 50% of the reported cases occurred in children between 6 and 10 years of age without sexual predilection. The main clinical presentations were abdominal mass and pain; the right lobe of the liver was involved in about 70% of the cases. Since then, limited cases have been reported because of the rarity of this tumor. Cytomorphologic features of these tumors are seldom described in the literature. To our knowledge,
Address correspondence to Ossama Tawfik, MD, PhD, Department of Pathology and Laboratory Medicine, 3901 Rainbow Blvd., Kansas City, Kansas 66160, USA, E-mail : [email protected]
Pediatric Pathology and Molecular Medicine 18: 221-229, 1999 Copyright 0 1999 Taylor & Francis
0190-2148/99 $12.00 + .OO 22 1
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
222 F. Fan et al.
there have only been three cases in which fine needle aspiration (FNA) cyto- logic findings of UES were described [3-51. More case studies are needed to highlight the diagnostic features of this unique neoplasm. We report here a case of undifferentiated (embryonal) sarcoma of liver in an 18-year-old male. The cytomorphologic criteria, histopathologic correlation, immuno- histochemical, and DNA ploidy analysis studies are discussed, with emphasis on diagnostic considerations of such unusual tumors and the potential pitfalls in the diagnosis by FNA cytology.
CASE REPORT
The patient is an 18 year-old white male who was transferred to the University of Kansas Medical Center for further evaluation of abdominal pain and a large liver mass. His illness started 3 to 4 months prior to his admission when he began to have right-sided pleuretic chest pain for which he was treated with two courses of antibiotics. His symptoms persisted and he subsequently developed intermittent nausea, vomiting, and early satiety. He also gradually lost 10 pounds over this time period and started to notice a gradually enlarging abdominal girth with associated tenderness. An outside computed tomography (CT) scan of the abdomen revealed a large heter- ogeneous mass in the ventral segment of the right lobe of the liver with no lymphadenopathy (Figure 1). His past medical history was significant for an allergy to penicillin. O n admission, the patient appeared chronically ill and in apparent distress with sunken eyes. He was afebrile and had neither cervi- cal nor axillary lymphadenopathy. His chest examination showed decreased breath sounds on the right lung base. Examination of his abdomen revealed a large mass in the right upper quadrant, with abdominal guarding. He had no peripheral edema and had no neurologic deficit. Additional radiologic studies included an arteriogram of the liver confirming the neoplastic nature of the lesion and a CT of the chest that revealed a small right pleural effusion without evidence of infiltrate, masses, or adenopathy.
His pertinent laboratory findings were alkaline phosphatase : 402 U/L (normal range: 25-110 U/L); AST: 52 U/L (normal range: 7-40 U/L); albumin: 2.6 (normal range: 3.5-5.0 g/dl); and total bilirubin: 1.2 (normal range: 0.2-1.0 g/dl). Serum AFP was not measured.
A fine needle aspiration under C T guidance revealed a highly necrotic specimen with occasional bizarre cells. A preliminary diagnosis of a malig- nant process was entertained at the time; however, a begnin reactive lesion with extensive necrosis and cavitation such as a liver abscess could not be excluded. The patient was taken to the operating room for exploratory lapa- rotomy on the following day. On opening the abdominal cavity, a well- encapsulated cystic mass nearly occupying the entire right hepatic lobe was noted with a densely adherent overlying omentum. During the initial explo-
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
Hepatic Undzferentiated Sarcoma 223
FIGURE 1. Dynamic CT scan shows a large heterogeneous tumor involving the right lobe of liver. The tumor is well defined and grossly cystic intervened with mesh-type soft tissue components without signifi- cant contrast enhancement (arrows). No calcification, hemorrhage, or fat tissue is present within the tumor. No additional masses or adenopathy are noted in the remaining liver and abdomen.
ration, the lesion was noted to be extremely friable. A fragment of the tumor was submitted for frozen sectioning to confirm its neoplastic nature. The entire tumor was then removed with a rim of normal liver without com- plications. A cholecystectomy and a pericholedochal lymph node biopsy were also performed. Further exploration of the rest of the abdominal cavity was unremarkable.
The patient tolerated the procedure well and his postoperative course was uneventful. Bone scan and bone marrow aspiration and biopsy were per- formed revealing no evidence of metastatic disease. The patient was dis- charged on the 7th postoperative day to be further evaluated by oncologists for outpatient chemotherapy. He was then treated with three courses of che- motherapy including MESNA, Adriamycin, Ifosfamide, and DTIC. The patient was subsequently re-explored 3 months later to rule out recurrence: multiple biopsies were taken from the liver, lymph nodes, and surrounding
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
224 F. Fan et al.
soft tissues with no evidence of disease identified. The patient remained without evidence of disease 12 months after resection of the liver mass.
MATERIALS AND METHODS
Fine Needle Aspiration (FNA)
FNAs of the liver mass were performed with 25-gauge needles under C T guidance. The aspirated material was transferred to glass slides ; some slides were air-dried and stained by a modified Wright stain (Diff-Quick) and the others were immediately fixed in 95% alcohol. A cell block was not obtained.
Tissue Sections and lmmunohistochemistry
Tissue sections from the partial right lobectomy specimen of the liver were fixed in 10% neutral buffered formalin and stained with hematoxylin and eosin and PAS stain. Immunoperoxidase staining was performed using a labeled-strepavidin-biotin peroxidase technique. The following monoclonal antibodies were used in the study: anti-AEl/AE3, vimentin, smooth muscle actin (HHF-35), S-100, and alpha-fetoprotein.
DNA Ploidy Studies
Scraped tumor tissues were stained by the Feulgen method. DNA content was analyzed with an image analyzer (CAS-200, Becton Dickinson Cellular Imaging System, San Jose, CA). The DNA content of 150 tumor cells was determined, and the DNA index was calculated.
RESULTS
Cytopathology
The smears from the FNA biopsy yielded a satisfactory specimen. They were cellular with loosely arranged isolated cells and clusters of cells. The cells showed significant variations in size and shape; some were round and spindle shaped. More strikingly, there were some large, markedly bizarre and even giant cells (Figures 2a and 2b). The nuclei were hyperchromatic and pleomorphic with coarse chromatin and prominent nucleoli. Atypical mitotic figures were seen occasionally. Extensive necrosis and marked acute inflam- mation were present in the background.
Histopathology
The right lobectomy specimen of the liver contained a well-circumscribed largely hemorrhagic, extensively necrotic mass, measuring 22 x 18 x 4.0 cm and weighing 2080 gm (Figure 3). About 60-70% of the tumor was necrotic.
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
Hepatic Undgerentiated Sarcoma 225
FIGURE 2. Aspiration smear of hepatic undifferentiated (embryonal) sarcoma. (a) Cellular aspirate showing loosely arranged isolated cells mixed with cohesive clusters of cells in a background of extensive necrosis and inflammation (Papaniclaou stain, x400). (b) Occasional multinucleated tumor giant cell with small amount of cytoplasm in a hemorrhagic background (Diff-Quick stain, x800).
Nonnecrotic tumor tissue was identified at the periphery of the tumor. The cut surface was variegated, solid, focally cystic, and gelatinous.
Microscopically, this tumor had a heterogeneous appearance with a pre- dominant solid component composed of compact spindle tumor cells (Figure
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
226 F. Fan et al.
FIGURE 3. Resected partial hepatectomy specimen nearly totally replaced by a well-circumscribed, hemorrhagic, extensively necrotic mass. Note the large areas with myxoid and cystic degeneration in the upper middle portion of the tumor.
4a). A more loosely arranged component with stellate cells in a myxomatous background also was present (Figure 4b). Smooth muscle-like fascicles and bundles were seen. The tumor cells showed similar pleomorphic features as in the FNA specimen with a high mitotic rate (averaging 5 per high power field). Numerous eosinophilic, extra- and intracellular globules were present with the tumor cells, which were PAS-positive and diastase resistant. There was no rhabdomyoblastic or lipoblastic differentiation. Entrapped normal hepatocytes and benign appearing dilated bile ducts in the tumor tissue were identified.
Immunohistochemical stains demonstrated that the tumor cells were focally positive for vimentin. They were negative for AEl/AE3, HHF35 (muscle actin), S- 100, and alpha-fetoprotein.
DNA Ploidy Results
DNA content analysis is a prognostic indicator for a wide variety of human neoplasms. Aneuploidy is usually associated with a poor prognosis. The imaging study of DNA content on this tumor demonstrated a DNA index of 2.72, indicating an aneuploid tumor.
DISCUSSION
Hepatic undifferentiated (embryonal) sarcoma is a distinct malignant liver tumor. Its clinical presentation, laboratory findings, and CT scan
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
Hepatic Undiferentiated Sarcoma 227
FIGURE 4. Histologic sections of the hepatic undifferentiated (embryonal) sarcoma showing areas com- posed of compact spindle tumor cells with occasional tumor giant cells (a) (Hematoxylin and eosin stain, x800). (b) Areas with the more loosely arranged component of the tumor in a myxomatous background (Hematoxylin and eosin stain, x200).
images are nonspecific, which may account for the usual late diagnosis of this tumor. Since this tumor is known for its poor prognosis and complete surgical resection is the treatment of choice, it is critical to make an early diagnosis to improve prognosis. The histogenesis of UES is still controversial [6]. Lauwers
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
228 F. Fan et al.
et al. recently proposed that it might arise from a mesenchymal harmatoma [7]. Fine needle aspiration can be very useful in this aspect and may be performed more in the future. However, because of the rarity of this tumor, the cytologic features are not very well described. T o our knowledge, only two papers have been published on fine needle aspiration cytology of this rare neoplasm [4, 51. The cytopathologic features also have been described in peritoneal washing in a case with primary UES [S].
In our fine needle aspiration findings, the cells are arranged loosely in a myxomatous background. The cells are primitive looking with pronounced pleomorphism. There are spindle cells, big bizarre cells, and tumor giant cells. The nuclei are hyperchromatic with coarse chromatin and prominent nucleoli. The histology sections showed the presence of characteristic numer- ous eosinophilic hyaline globules of various sizes, which were not noted in the FNA biopsy. I t is noteworthy to mention that there were extensive necrosis and marked acute inflammation in the background of aspiration smears. Our findings are similar to those described by Sola-Perez et al. [5]. We think these cytologic features have recapitulated the characteristic histologic fea- tures of UES, and FNA could be used in future evaluation of suspected hepatic UES.
The differential diagnoses of this tumor include malignant processes such as hepatoblastoma, hepatoma, hemangioendothelioma, rhabdomyosarcoma, malignant fibrous histiocytoma (MFH) and metastatic tumors and benign lesions including mesenchymal hamartoma and a liver abscess secondary to infections or other inflammatory conditions. The patient’s age, clinical and radiologic presentations, tumor location, cytologic and histopathologic fea- tures, and immunohiostochemical stains should be helpful in making a correct diagnosis. As seen in this case, a cellular cytologic specimen with abundant malignant cells is diagnostic for a malignant process. The lack of cytologic and histopathologic features suggestive of epithelial, smooth muscle, or rhabdomyosarcomatous differentiation and the negativity for alpha-feto- protein and smooth muscle markers are helpful features in excluding hepa- toma, leiomyosarcoma, and rhabdomyosarcoma.
Multinucleated giant cells could be seen in either MFH or UES. O n occasions, it would be almost impossible to distinguish one from the other on cytologic grounds. Several authors have mentioned a close relationship between UES and MFH [6, 81. However, liver MFH is extremely rare in this pediatric age group. Primary UES is mainly cystic intermingled with soft tissue components in CT. The tumor is primarily hypovascular angi- ographically and may show small areas of increased tumor vascularity. Dif- ferentiation between UES and mesenchymal hamartoma, however, could be difficult radiologicaly, as both of them would show identical radiologic find- ings.
In summary, we report a case of hepatic undifferentiated (embryonal)
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
Hepatic Undzfferentiated Sarcoma 229
sarcoma in a n 18-year old male. Cytopathologic features observed in this case and described in other reported cases are distinctive for this tumor. Fine needle aspiration can be used as a reliable screening tool for early diagnosis of this rare tumor.
REFERENCES
1. Stanley RJ, Dehner LP, Hesker AE. Primary malignant tumors (mesenchymoma) of the liver in childhood : an angiographic-pathologic study of three cases. Cancer
2. Stoker JH, Ishak KG. Undiflerentiated (embryonal) sarcoma of the liver: report of 31 cases. Cancer 1978;42:336-348.
3. Allen EA, Clark DP, Ali SZ. Primary hepatic undifferentiated embryonal sarcoma : cytopathologic findings in peritoneal washings. Acta Cytol
4. Pieterse AS, Smith M, Smith L, Smith P. Embryonal (undifferentiated) sarcoma of the liver : fine-needle aspiration cytology and ultrastructural findings. Arch Pathol Lab Med 1985;109:677-680.
5. Sola-Perez J, Perez-Guillermo M, Gimenez-Bascunana A, Garre-Sanchez C. Cytopathology of undifferentiated (embryonal) sarcoma of the liver. Diagn Cyto- pathol 1995;13:44-51.
6. Aoyama C, Hachitanda Y, Sat0 JK, Said JW, Shimada H. Undifferentiated (embryonal) sarcoma of the liver. A tumor of uncertain histogenesis showing divergent differentiation. AmJ Surg Pathol 1991 ;15:615-624.
7. Lauwers GY, Grant LD, Donnelly WH, Meloni AM, Foss RM, Sanberg AA, Langham MR. Hepatic undifferentiated (embryonal) sarcoma arising in a mesen- chymal hamartoma. Am J Surg Pathol 1997;21: 1248-1254.
8. Keating S, Taylor GP. Undifferentiated (embryonal) sarcoma of the liver. Ultra- structural and immunohistochemical similarities with malignant fibrous histiocy- toma. Hum Pathol 1985 ; 16 : 693-699.
1973;32:973-984.
1998;42(2) ~449-451.
Feta
l Ped
iatr
Pat
hol D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y U
nive
rsity
of
Uls
ter
at J
orda
nsto
wn
on 1
1/13
/14
For
pers
onal
use
onl
y.
