Epithelioid Hemangioendothelioma
Anna-Luise Katzenstein
SUNY Upstate Medical Center
Syracuse, NY
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Clinical History:
This 46 year old woman complained of intermittent chest pain, cough, and a 10 pound
weight loss over two months. She was thought to have a right upper lobe pneumonia, and she was treated
with antibiotics. There was no response after 10 days, and a subsequent chest CT showed a large, 8 cm
mass in the right upper lobe. Additionally, there were several smaller, 5-6 cm nodular masses in the
left upper, right upper and right lower lobes. Core biopsy of the large mass showed a poorly
differentiated squamous cell carcinoma. A core biopsy was also taken from a separate 5mm nodule in the
right lower lobe, and the slide presented is from that lesion.
Case 3 - Figure 1 Low magnification view showing partial replacement of a portion of lung parenchyma by a well- demarcated process containing extensive central hyalinization. The adjacent lung is normal.
Case 3 - Figure 2 Higher magnification shows the collagenous appearance of the central portion of the lesion while highlighting the cellular peripheral portion. Although the lung architecture is effaced in the central areas, the lesion fills alveolar spaces at the periphery leaving adjacent alveolar septa intact.
Case 3 - Figure 3 High magnification of the central portion of the lesion showing deposition of amorphous, eosinophilic material containing almost no cells.
Case 3 - Figure 4 High magnification of the cellular peripheral areas showing the characteristic spindle to epithelioid cells with moderate eosinophilic cytoplasm embedded in myxochondroid and collagenous stroma.
Case 3 - Figure 5 Pancytokeratin stain showing positive staining in alveolar pneumocytes surrounding the tumor, but the tumor is negative.
Case 3 - Figure 8 High magnification of the tumor cells showing epithelioid to spindle cell configeration and prominent eosinophilic cytoplasm.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
This biopsy shows
partial replacement of lung parenchyma by a relatively bland appearing, predominantly collagenous
process. The center of the lesion is nearly acellular, composed of dense collagen deposition, with rare
cells, mainly fibroblasts, and minimal residual recognizable lung parenchyma. The process is more
cellular peripherally where it abuts adjacent uninvolved lung. In this area a mixture of spindle to
epithelioid cells is present within chondromyxoid stroma. The process in this area is partially
surrounded by intact alveolar septa thus indicating growth within alveolar spaces. The component cells
have bland nuclei and a moderate amount of eosinophilic cytoplasm. Mitotic figures are not seen.
Immunohistochemical stains for cytokeratin outline pneumocytes lining the surrounding alveolar septa, but
are negative in the tumor cells. Stains for CD31 and CD34 are strongly positive in the tumor cells.
Differential Diagnoses:
On routine H and E stained slides a number of neoplasms as well as
non-neoplastic processes enter the differential diagnosis. Among the neoplasms, chondrosarcoma,
melanoma, mesothelioma, and various other primary and metastatic carcinomas and sarcomas are
considerations. Among the non- neoplastic lesions organizing infarcts, organizing pneumonia, hyalinized
granulomas, and amyloid nodules may enter the differential diagnosis.
Final Diagnosis:
Epithelioid hemangioendothelioma
Case Discussion:
With the increasing use of core needle biopsies for diagnosing nodular lung
lesions [1], pathologists need to be familiar with a wide range of unusual neoplastic and
non-neoplastic lesions that may be encountered. In some cases, like the current one, the biopsy may be
taken to stage a known primary carcinoma, and the results will be important determining prognosis and
choosing treatment. In other situations the biopsy may be taken to diagnose single or multiple nodular
densities, some of which may be quite small, often identified incidentally on chest computed tomography
(CT) exams.
In the current case, the small nodular lesions were suspected clinically to represent metastases from
the large squamous cell carcinoma, and a biopsy was performed to determine whether the carcinoma was
resectable. Although pulmonary EHE is a malignant tumor, it is low-grade and slowly progressive, and its
presence would not preclude resection of the carcinoma. Unfortunately, however, further work-up in this
patient revealed brain metastasis indicative of Stage IV disease, and she received palliative radiation
and chemotherapy.
Review of the Literature/Treatment Options:
Pulmonary EHE, like its counterpart in
soft tissue and other sites is a slow growing, low-grade malignant tumor. [5] It was first
described by Dail and Liebow in abstract form in 1975 [3], and subsequently reported in more
detail in 1983 [4]. Because of its frequently intraalveolar growth pattern as well as vascular
invasion, Dr. Liebow initially considered it to be a form of angioinvasive bronchoalveolar carcinoma,
hence the early term, "intravascular bronchoalveolar tumor" or "IVBAT". Others before then reported it
under the rubric of "pulmonary deciduosis" or chondrosarcoma.
Although more than 90 cases have been reported since the initial description, [1] there are
only two large series of 20 [4]
and 21 [8] patients, respectively. Overall, the mean age
at presentation is about 40, but the condition can occur in children as well as the elderly. There is a
female predominance with a female:male ratio ranging from 1.6:1 to 4:1. About half of all reported
patients are asymptomatic, with as many as 75% being asymptomatic in one series, and the lesion is often
detected incidentally on radiographs (usually CT's) taken for other reasons. The typical radiographic
finding is that of nodular densities that are usually small measuring one cm or less in diameter, and
they are multiple (85%) and bilateral (80%) in most cases. Rarely, solitary masses mimicking primary
lung carcinoma or pleural thickening mimicking mesothelioma are encountered. [11] The tumors are
slowly growing, and long survival is possible even when multiple. Kitaichi et al [8] reported
80% 5- year survival compared to 45% in Dail et al's [4] initial report. Patients who are
symptomatic at presentation and/or have pleural effusions have a worse prognosis.
[1,
8]
There is
no effective treatment other than excision.
Histologically, pulmonary EHE is characterized by sheets of medium-sized epithelioid appearing cells
embedded in a chondromyxoid to collagenous stroma. The cells are usually round with small, bland nuclei
and a moderate amount of eosinophilic cytoplasm. Occasionally, intracytoplasmic lumens can be seen.
Sometimes spindling occurs in the cells but it is generally focal. Spindle cells were associated with a
worse prognosis in one study. [8] Mitotic figures are usually not present, and cytologic atypia
is usually not prominent. The process grows mainly within alveolar spaces, a pattern that is best
appreciated at the junction of the tumor with normal lung where intact alveolar septa are seen
surrounding the tumor nests. Sometimes residual alveolar septa can be identified in the deeper portions
of tumor, especially if elastic tissue stains are examined. The tumor is characteristically most
cellular near the margin with normal lung, while the central portions show varying degrees of
hyalinization and/or infarct-like necrosis. Vascular invasion with occlusion is common, occurring in
about one fourth of cases.
Immunohistochemical stains are helpful in difficult cases and especially on small biopsy specimens,
although they are usually not necessary in classic cases. The tumor cells stain strongly for endothelial
markers, including Factor VIII, CD 34, CD31, and Fli-1. CD31 and Fli-1 are the most sensitive, being
reported positive in 100% of cases in some studies.
[7,
10]
Cytokeratins can be focally positive
in up to 38% of cases, and focal positivity for S-100 and EMA has been reported in rare
cases.
[1,
7,
10]
As with most tumors a panel of immunostains is recommended for definitive
diagnosis especially to separate EHE from the various lesions in the differential
diagnosis.
[2,
7]
Pulmonary EHE cannot be distinguished histologically or by immunohistochemistry from metastatic EHE
that is primary in extrathoracic sites. [9] A search for extrathoracic primaries, especially in
liver or soft tissue, therefore may be warranted before assuming that the tumor is primary in the lung.
Conclusion(s):
Pulmonary EHE is a rare, slowly growing malignant neoplasm that may mimick an number
of neoplastic and non-neoplastic conditions. The use of immunohistochemistry, especially endothelial
markers, usually clarifies the diagnosis in difficult cases.
References:
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