Category: Case of the Month

History: A 32 year old previously healthy Hispanic male presented with a 3-week history of dyspnea upon exertion.  A CT-scan showed a mass in the left cardiac atrium which extended into the pulmonary veins.  The tumor was well encapsulated and attached to an atrial appendage.  It measured 6 x 5 x 4 cm and was solid, pale pink-tan with gelatinous regions.  Foci of necrosis and hemorrhage were present.  The surgeon was not able to completely excise the mass.

The neoplasm was microscopically remarkable for having a large number of sarcoma patterns (Fig. 1).  There was a blending of spindle-cell sarcoma with osteosarcoma and chondrosarcoma (Fig. 2,3) Other areas consisted of sheets of uniform fusiform cells growing in long sweeping fascicles with a faint herringbone pattern (Fig. 4).  Yet other regions showed cells with more pleomorphism and abundant eosinophilic cytoplasm with faint longitudinal and cross striations (Fig. 5).

The cartilaginous, but not the spindle cell areas marked for S100 protein. An actin stain was weakly positive and a desmin stain was strongly positive, especially in the more pleomorphic spindle cell areas (Fig. 6)

Diagnosis: “Chondrosarcoma, Osteosarcoma, Myosarcoma and Fibrosarcoma of the atrium (‘Malignant Mesenchymoma’)”

Timothy R. Smith, MS3 and Donald R. Chase, MD
Department of Pathology and Human Anatomy 
Loma Linda University and Medical Center, Loma Linda, California 
California Tumor Tissue Registry, Loma Linda, California

Discussion: Primary tumors of the heart are very rare.  They are mostly benign with relative frequencies of:

myxomas (78%)
sarcomas of any type (10%)
fibroma (3%)
lipoma (3%)
vascular tumors (2%), and 
rhabdomyoma (2%).   

Most cardiac tumors present with non-specific symptomology reflecting disruption of the conduction system or blockage of blood flow.  In addition, high grade sarcomas may also present with distant metastasis, especially when they involve the great vessels of the heart.  When malignant, cardiac tumors (virtually all of which are sarcomas) are usually of a “pure” histologic type and the combination of sarcoma subtypes in our presentation case is exceedingly rare.  Although it is common practice to identify the specific type of sarcoma by morphologic and immunohistochemical patterns, the exercise of doing so is of little clinical value.  In addition to location of a sarcoma in the great vessels, low resectibility, a high mitotic rate and the presence of necrosis portend an accelerated aggressive behavior.

There is still debate about the classification of soft tissue tumors that show more than one tumor type.  In soft tissue, the uterus, and other in other organs, when both an epithelial and sarcomatous component are present the term, “carcinosarcoma” is still in use.  In soft tissue the term, “malignant mesenchymoma” has been used since it was first coined by Stout in 1948.  He defined these complex neoplasms as “non-epithelial malignant tumors showing two or more unrelated tissue types in addition to a fibrosarcomatous element”  Stout and Lattes later changed this definition to mean sarcomas composed of two or more unrelated tumor elements, with or without a fibrosarcomatous component. More recently, the World Health Organization decided that “malignant mesenchymoma” was a vague term and did not reveal the various morphologies of the mixed sarcomas.  The current thought, expounded by Weiss, Goldblum, and Fletcher is that the term “malignant mesenchymoma” should be deleted from the classification scheme of soft tissue tumors. 

Differential Diagnosis of Cardiac Neoplasms:

• Cardiac Rhabdomyomas usually arise in the myocardium of children, generally below the age of five years and is sometimes associated with tuberous sclerosis. The cells are usually “bubbly”, stain for desmin, and may have striations.  Mitotic figures are virtually non-existent.  Occasional rhabdomyomas may spontaneous regress, usually by maturation into more normal-appearing myocytes. 
 
• Cardiac Fibromas also arise mostly in children and may be associated with adenoma sebaceum of the skin and kidney tumors.  They consist of a uniform proliferation of fibroblasts without significant mitotic activity.  They lack either a cartilaginous or an osseous matrix.

• Myxomas have varied gross appearances and are smooth or lobular, firm or gelatinous, and contain a myxoid stroma. They account for the majority of primary cardiac tumors. Seventy-five percent are found in left atria.  Curiously, benign myxomas usually are found in the left side of the heart, while sarcomas are usually found in the right side.

• Vascular neoplasms may be benign (hemangioma) or malignant (angiosarcoma) and when large, may interrupt blood flow through the heart.  Angiosarcoma is particularly prone to early metastases.  Both tumors stain for vascular markers such as CD31, CD34 and HFVIII.

• Lipomas usually originate in the endocardium or epicardium and have a broad pedunculated base.  They consist of mature, adult-type fat.

• Pericardial cysts may mimic a cardiac tumor or pericardial effusion on chest x-ray.  They are usually asymptomatic, although some cause compressive symptoms (eg, chest pain, dyspnea, cough).  The center of the process is of blood-tinged fluid which is bounded by pericardial-type cells. 

• Sarcomas are usually vimentin-positive and are composed of spindled cells of varying pleomorphism.  A negative desmin stain tends to exclude myogenous origin and a negative S100 stain helps in the exclusion of neural tumors and melanoma.  A negative epithelial stain helps rule out spindled carcinomas and synovial sarcoma.  Osseous and/or cartilaginous matrix formation rules out the previously mentioned benign cardiac tumors.

• Teratomas usually occur in midline structures such as the anterior mediastinum but rarely arise in the heart.  By definition, these germ cell tumors contain tissue types representing all three germ layers.

A high index of suspicion is necessary for early diagnosis of these cardiac neoplasms.  Patients with signs of cardiac obstruction, chest pain or discomfort, or dyspnea should have appropriate radiologic and laboratory work-ups.  But even with early diagnosis, sarcomas do poorly, and even with positive indicators such as low mitotic rate, low levels of necrosis, presence in the left side of the heart, and good resectibility, the survival rate of cardiac sarcomas is under five years.  Cardiac transplant is a last measure for patients with Unmanageable primary cardiac tumors. 

Suggested Reading:

Weiss SW, Goldblum JR. Enzinger & Weiss’ Soft Tissue Tumors 5th ed: 1213-1214, 2008.

Stout AP. Mesenchymoma: the mixed tumor of mesenchymal derivatives. Annu Surg: 127:278-90, 1948.

Stout AP, Lattes R. Tumors of the soft tissues. In: Firminger GI, ed. Atlas of Tumor Pathology. 2nd series. Fascicle 1. Washington, DC: Armed Forces Institute of Pathology;: 172-5, 1967

Virmani, Burke, Farb, Atkinson. Tumors and tumor-like lesions of the heart and great vessels. Cardiovascular Pathology 2nd ed;: 424-458, 2001.

Merck online manual section cardiovascular disorders, subject Cardiac tumors, Topics Cardiac tumors, 2008.

History: A 43-year-old gravida 0 woman with a history of menorrhagia was found to have a 3.5 cm left retroperitoneal, periaortic mass on abdominal CT six years previously (Fig. 1).  She underwent CT-guided biopsy of the left periarotic mass and was diagnosed to have an epithelioid and spindle cell neoplasm consistent with epithelioid leiomyosarcoma.  Despite chemotherapy the retroperitoneal lesion persisted, though no progression was seen by CT follow-up.  A current pelvic examination demonstrated a mobile anteverted enlarged uterus without adnexal masses. A vaginal hysterectomy with bilateral salpingo-oophorectomy was performed.

The 920 gm, 19.0 x 18.0 x 8.0 cm uterus contained multiple serosal, intramural and submucosal nodules with pale-tan whorled cut surfaces measuring up to 8.0 cm in diameter (Fig. 2a). Additionally, the anterior lower uterine segment was distorted by numerous firm, poorly-circumscribed nodules ranging from 0.2 to 1.0 cm in diameter.  The excised 6.0 cm left periaortic mass proved to be an enlarged lymph node with fleshy-pink, homogeneous cut surfaces (Fig. 2b).

Microscopically, the lower uterine segment was extensively infiltrated by numerous small nodules with irregular tongues invading the adjacent myometrium (Fig. 3).  The nodules were densely cellular with a “blue” appearance at low magnification and areas with prominent stromal hyalinization (Fig. 4).  Composed of a spindle cell proliferation, the neoplasm was punctuated by a plexiform capillary network with edematous change (Fig. 5).  Spindle cells featured uniform oval to round nuclei, vesicular chromatin, small nucleoli and elongated inconspicuous cytoplasm (Fig. 6).  No striking pleomorphism and relatively few mitotic figures were seen ranging from 2 to 5 mitoses per 10 hpf with occasional atypical forms.  No hemorrhagic necrosis, definitive vascular invasion, sex cord-like arrangements, or epithelioid differentiation was identified.  The periaortic lymph node was predominately replaced by neoplastic cells with identical histology as the lower uterine segment nodules (Fig. 7).  Immunohistochemical studies performed on both the uterine and lymph node tumors exhibited identical patterns: strong positivity for CD10, focally positivity for SMA, and negative staining for desmin (Fig. 8a & 8b).  A Ki67 proliferative index demonstrated low activity (~ 10%).

Diagnosis: “Low-grade endometrial stromal sarcoma with retroperitoneal periarotic lymph nodes metastasis”

Mingyi Chen M.D., Evelyn Choo M.D., Amita T. Mistry, M.D., Donald R. Chase, M.D.
Department of Pathology, Loma Linda University and Medical Center
California Tumor Tissue Registry, Loma Linda, California

Discussion: Endometrial stromal tumors are the second most common category of mesenchymal tumors of the uterus; however, they only account for approximately 10% of all uterine sarcomas.  Low-grade endometrial stromal sarcoma (LGESS) occurs in younger women (median age ~40 years) compared to other uterine neoplasms such as carcinosarcoma (malignant mullerian mixed tumor), leiomyosarcoma, or endometrial carcinoma.  Patients typically present with abnormal vaginal bleeding, pelvic pain, and a clinical impression of uterine leiomyomata due to an enlarged uterus with an irregular contour.

Endometrial stromal tumors are divided into two classes based on the presence of circumscribed margins (stromal nodule), or infiltrating margins with or without vascular intrusion (stromal sarcoma).  The two lesions are otherwise indistinguishable histologically.  Infiltration is seen as irregular, jagged islands or tongues of neoplastic stromal cells between the smooth muscle bundles of the surrounding normal myometrium.   Determining myometrial infiltration can be problematic, especially when there is subtle interdigitation of stromal and smooth muscle cells at a compressive margin examined at high magnification, which should not be counted as an infiltrative margin.  A diagnosis of stromal sarcoma is rarely possible in curettage and biopsy specimens since margin evaluation is questionable.  For vascular involvement, clumps of tumor cells must be present in spaces within the myometrium.

LGESS is comprised of uniform, oval to spindle-shaped cells with inconspicuous cytoplasm and round to oblong nuclei that are morphologically, ultrastructurally and immunohistochemically identical to endometrial stromal cells found in proliferative endometria.  This monotonous cellular proliferation is interrupted by a characteristic regular network of delicate ramifying small vessels resembling spiral arteries and capillaries.  The presence of fragments of proliferative phase endometrial stroma without glands in curettage or biopsy specimens raises the possibility of an endometrial stromal tumor.  Significant cytological atypia and pleomorphism are absent as well as stainable glycogen and mucin.  Occasionally, an abundance of distinctive hyalinized osteoid-like collagen is present, and may be so extensive as to reduce the cellular component to attenuated chains of cells, resembling a hyalinized leiomyoma. This pattern of hyalinization may be preserved in pelvic recurrences and pulmonary metastases.  Foam cells may be present in stromal neoplasms and are morphologically identical to the foam cells seen in endometrial hyperplasia and carcinoma.  Neoplastic cells are positive for CD10, almost always estrogen and progesterone receptor positive and focally positive for actin.

The most common cytogenetic alteration observed in low-grade endometrial stromal tumors is the t(7;17)(p15;q21) translocation, resulting in the fusion of the JAZF1 and JJAZ1 genes.

Differential Diagnosis:

•    Benign smooth muscle tumors: In a uterine tumor composed of uniform spindle cells with circumscribed margins, the distinction between smooth muscle and endometrial stromal tumors is less critical since both leiomyoma and endometrial stromal nodules are benign. With infiltrating margins, the distinction between either a leiomyoma or a LGESS is clinically significant.  Cellular leiomyomata can be especially problematic.  As in the current case, the concomitant presence of extensive leiomyomas can cause difficulties in the diagnosis of endometrial stromal sarcoma.  Small tissue sampling can also add to the complexity.  Positive staining of desmin, smooth muscle actin, and/or CD10 immunostains can be helpful in distinguishing LGESS from smooth muscle neoplasms.  If the cellular lineage remains ambiguous, it may be prudent to assign the tumor to the low-grade stromal category, particularly if there are tongue-like islands infiltrating within the myometrium or vascular invasion is present.  Though unequivocal smooth muscle elements may be seen within otherwise typical endometrial stromal neoplasms, such tumors behave more like LGESS than their smooth muscle counterparts (such as intravascular leiomyomatosis, leiomyomatosis, or leiomyomas).  Intravascular leiomyomatosis is far less common than endometrial stromal sarcoma; and should not be diagnosed unless tumor cells show unambiguous smooth muscle differentiation.

•    Leiomyosarcoma: LGESS lacks significant cytological atypia and is less mitotically active when compared to leiomyosarcoma.  Mitotic indices more than 10 mitotic figures/10 hpf are unusual in endometrial stromal sarcoma but do not exclude the diagnosis.  In addition, the tumor cells in leiomyosarcoma have more abundant cytoplasm, and can often be focally arranged in long fascicles.  Angioinvasive leiomyosarcoma is distinguished from endometrial stromal sarcoma by its greater cytologic atypia, and lack of plexiform vasculature.

•    Adenomyosis:  Occasionally, adenomyotic foci do not contain glands, raising the possibility of LGESS.  Stromal nodules and sarcomas produce mass lesions, whereas small foci of gland-free endometrial stroma in the absence of a mass within the myometrium are almost always a manifestation of adenomyosis.  Looking for the characteristic smooth muscle hypertrophy that often accompanies adenomyosis as well as gland-containing lesions elsewhere in the myometrium usually establishes the correct diagnosis.  Very rarely, fragments of benign proliferative phase stroma without glands are found within myometrial vessels.  As long as no mass lesion is identified and the intravascular fragments are microscopic, this phenomenon is undoubtedly a manifestation of adenomyosis.

•    Hemangiopericytoma:  Vasculature resembling endometrial spiral arterioles is uniformly distributed throughout LGESS potentially leading to a mistaken diagnosis of hemangiopericytoma.  Immunohistochemical studies can establish the diagnosis with CD10 staining the endometrial stromal cells in LGESS, and the weak and patchy staining of CD34 in hemangiopericytoma.

•    Adenosarcoma and malignant mullerian mixed tumor (MMMT): LGESS with foci of glandular differentiation raises the differential diagnostic consideration of adenosarcoma which contains endometrial stromal cells as the mesenchymal component.  Glands in endometrial stromal sarcoma are usually sparse and small without surrounding stromal condensation, whereas those of adenosarcoma often feature periglandular stromal condensation and tend to be large and dilated.  However, when glands are numerous and stromal condensation is questionable, considerable overlap exists between these two neoplasms with malignant mesenchymal elements.  LGESS typically expresses estrogen and progesterone receptors, but MMMT shows marked pleomorphism and a high mitotic rate.  Prognostically, both LGESS with glands and adenosarcoma with a low-grade stromal proliferation are low-grade neoplasms, though the prognosis worsens when the primaries occur in extra-uterine sites.

LGESS is characterized by indolent growth with up to half of all patients developing one or more pelvic or abdominal recurrences, some as much as 20 years later.  Median interval for recurrence is 3-5 years.  Women with stage I disease have >80% survival, while survival is less favorable (~50%) when advanced stage disease is present.  Pulmonary metastases occur in 10% of stage I tumors.  The single most important prognostic factor is the stage at presentation, and risk of recurrence is determined by both stage and the type of surgical procedure.  Adnexal spread may not be appreciated during the operation and pelvic recurrence occurs more frequently with ovary conservation.  Both recurrent and metastatic disease can remain localized for long periods and are amenable to successful treatment by resection, radiation therapy, progestin therapy or a combination thereof.  Curative therapy is not guaranteed by bland histology and low mitotic indices.  Although progestin therapy may be effective in cases with progesterone receptor expression, chemotherapy alone is usually ineffective.

Suggested Reading:

1.    Kempson RL, Hendrickson MR. Smooth muscle, endometrial stromal, and mixed Mullerian tumors of the uterus. Modern Pathology. 13(3):328-42, 2000.
2.    Clement PB, Young, RH. Atlas of gynecologic surgical pathology. 1st Edition, 177-210, 2000.
3.    Kurman RJ. Blaustein’s pathology of female genital tract. 5th Edition, 583-605, 2002.
4.    Robboy SJ, Anderson MC, Russell P. Pathology of the female reproductive tract. 1st Edition, 370-80, 2002.
5.    Kurihara S, Oda Y, Ohishi Y, Iwasa A, Takahira T, Kaneki E, Kobayashi H, Wake N, Tsuneyoshi M. Endometrial stromal sarcomas and related high-grade sarcomas: immunohistochemical and molecular genetic study of 31 cases. Am J Surg Pathol. 32(8):1228-38, 2008.

History: A 28 year-old woman presented with a palpable mass in the deep tissues of the left thigh. A 4.6 x 3.5 x 2.8 cm ovoid rubbery soft tissue mass was removed. Its perimeter was well-circumbscribed and was partially covered by gray-brown fragments of skeletal muscle. The cut surface was glistening and pink-white. Rare microcysts were seen.

The tumor was sharply demarcated from surrounding skeletal muscle and had a variably thick capsule (Fig. 1–2b). Highly cellular regions were present in close proximity to less cellular, fibrotic regions (Fig. 3). Some regions had a vague storiform growth pattern, but generally the tumor was present in diffuse sheets. Individual cells had round to polygonal nuclei with limited spindling (Fig. 4). Myxoid areas were only infrequently encountered. Low levels of mitotic activity are observed, mostly in the hypercellular regions. Neither atypical mitotic figures nor bizarre nuclear pleomorphism were seen. Of interest were the large, rosette-like structures with hyalinized centers (Figs. 2a, 5).

Diagnosis: “Low-Grade Fibromyxoid Sarcoma With Hyalinizing Giant Rosettes”

Timothy R. Smith, MS3 and Donald R. Chase, MD
Department of Pathology and Human Anatomy
Loma Linda University and Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California

Discussion: Low-Grade Fibromyxoid Sarcoma (LGFMS) is a rare, recently-described soft tissue tumor that is now being more completely characterized. First described by Evans in 1987, LGFMS is also known as “Evans tumor”. The tumor usually arises in young to middle-aged adults, but has a range from 3 to 78 years. Males are more commonly affected than females. The lower extremities are the most common site, especially the thigh, although the tumor has now been reported in virtually any location. Although Evans original description did not include rosettes, the tumor has subsequently been found to have large, hyalinizing giant rosettes. This variant was subsequently described 10 years later in a paper by Drs. Lane, Shannon and Weiss et.al (1997) as “hyalinizing spindle cell tumor with giant rosettes”. Three years later (2000), Drs Folpe and Weiss proposed a unified theory that the two tumors are likely the same, both behaving as low grade sarcomas. Deceptively bland, both Dr. Evans and Dr. Lanes’ tumor types have high recurrence rates and may eventually dedifferentiate into a higher grade sarcoma. In addition to tumor morphologies that are illustrated in this paper (Figs. 1-5), a minority of the cases show increased perivascular cellularity, moderate nuclear pleomorphism (more often in recurrent tumors), and, in myxoid areas, a rich capillary vascular network.

LGFMS is routinely positive for vimentin and may be focally positive for smooth muscle actin. Decoration for S-100 is uncommon but may occur in regions adjacent to rosettes. The tumor is uniformly negative for CD34, EMA, desmin and cytokeratin.

A translocation occurs in up to 88% of the cases and is usually expressed as t(7;16)(q34;p11) FUS-CREB3L2 fusion gene. Genetics losses of 13q also occur (Kiuru-Kuhlefelt et al., unpublished observations.)

The differential diagnosis of LGFMS includes low grade fibroblastic/myofibroblastic tumors and neoplasms with myxoid characteristics:

• Desmoid-type fibromatosis is also composed of uniform, bland cells with minimal mitotic activity. The major difference, though, is the much more organized fascicular growth of fibromatosis and the usual lack of myxoid regions and alternating zones of cellularity. Large rosettes do not occur in desmoid tumors, and significant pleomorphism is absent. B-catenin is negative in LGFMS but may be positive in fibromatosis.

• Neurofibroma (NF) almost always shows staining for S-100 while LGFMS only shows localized S-100 staining near rosettes. The diffuse form of neurofibroma may have Wagner-Meisner bodies which are lacking in LGFMS, and when NF is associated with van Recklinghausen’s disease, it may assume a plexiform pattern, also non-existent with LGFMS. Finally, the nuclear characteristics of peripheral nerve sheath tumors are uniquely different showing asymmetrical shapes resembling commas, apostrophes, and sine waves.

• Low-grade myxoid MFH (myxofibrosarcoma) has considerably more nuclear atypia and a more extensive myxoid matrix (generally more than 50% of its area). It uniformly lacks rosettes.

• Low-grade bland myxoid lesions can be a problem, since myxoid change may occur in virtually every type of mesenchymal neoplasm. LGFMS is characterized by alternating hypercellular/fibrous and myxoid areas and by the occasional swirling whorled cell growth pattern. Negative immunostains for S100, desmin and cytokeratin may help in excluding myxoid variants of neurofibroma, schwannoma, leiomyoma and mucinous carcinoma.

• Intramuscular and juxta-articular myxomas have much lower cellularity, no organized growth pattern and a paucity of blood vessels/capillaries. Since they have no hypercellular regions, they lack the alternating fibrous and myxoid areas that LGFMS possesses. These myxomas have colorfully been described as being “bags of water.”

LGFMS is a slow growing tumor with a deceptively benign appearance. Its early recognition as a sarcoma is vital since only complete surgical extirpation is initially adequate to prevent recurrence. Although recurrence and/or metastasis may be expected (Evans’ 1993 study showed 7/12 with distant spread), the tumor is indolent and potentially curable if caught early and completely excised.

Suggested Reading:

Evans HL. Low-grade fibromyxomas. A report of two metastasizing neoplasms having a deceptively benign appearance. Am J Clin Pathol 88:615, 1987

Evans HL. Low-grade fibromyxoid sarcoma. A report of 12 cases: Am J Surg Pathol; 17: 595-600, 1993.

Lane KL, Shannon RI, Weiss SW. Hyalinizing spindle cell tumor with giant rosettes: a distinctive tumor closely resembling low-grade fibromyxoid sarcoma. Am J Surg Pathol 21:1481, 1997.

Folpe AL, Lane KL, Paull G, Weiss SW, et al. Low grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high grade areas. Am J Surg Pathol 24(10):1353-1360, 2000.

Kempson RL, Fletcher CDM, Evans HL, et al: Tumors of the Soft Tissues. Atlas of tumor pathology. Third Series. 30. 99-104, 2001.

Miettinen M. Malignant and Potentially Malignant Fibroblastic and Myofibroblastic Tumors. Diagnostic Soft Tissue Pathology chap 7:193-194, 2003

Perigny M, Dion N, et al. Low grade fibromyxoid sarcoma: a clinico- pathologic analysis of 7 cases. Ann Pathol 26(6):419-25, 2006.

Matsuyama, A, Hisaoka, M, et al. Molecular Detection of FUS-CREB3L2 Fusion Transcripts in Low-grade Fibromyxoid Sarcoma Using Formalin-fixed, Paraffin-embedded Tissue Specimens. Am J Surg Pathol 30(9):1077-1084, 2006.

Downs-Kelly E, Goldblum JR, Patel RM, Weiss SW, et al: The utility of fluorescence in situ hybridizations (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol 32(1) 8-13, 2008.

History: A 42-year-old woman with a one month history of dry cough was radiographically thought to have a left cardiac myxoma and bilateral hydrothorax.  At surgery, however, she was found to have a 7.0 x 6.0 x 4.5 cm gray fleshy solid mass in the left pulmonary vein which extended into the left atrium.

Microscopically, the tumor grew in broad sheets and fascicles and was composed of spindled and epithelioid cells (Fig. 1).  Pleomorphic cells had blunt-ended nuclei and bizarre atypical nuclei with conspicuous nucleoli and a high mitotic rate.  The cytoplasm was eosinophilic.  Areas of tumor necrosis and dilated vessels with hemorrhage were also seen (Fig. 2, 3).  Immunohistologically, the lesional cells were strongly and diffusely positive for desmin and focally marked for smooth muscle actin (Fig. 4).  The tumor was negative for S100.

Diagnosis: “Pulmonary vein leiomyosarcoma”

Jin Guo, MD and Donald R. Chase, MD
Department of Pathology and Human Anatomy
Loma Linda University and Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California

Discussion: Although leiomyosarcoma of the pulmonary vein is extremely rare, it is the most common of primary pulmonary vein neoplasms.  Including the present case, there are only 20 cases of pulmonary vein leiomyosarcoma reported worldwide.  Of the non-leiomyosarcoma tumors of pulmonary vein origin, only single cases of angiosarcoma, lipomyxosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma and leiomyoma have been reported.

Cardiac leiomyosarcoma is very rare occurring in less than 0.2% of all cardiac tumors and generally favoring the left atrium.  It may secondarily invade the pulmonary veins, mitral valve, or even the lung.  The average reported patient age of pulmonary vein leiomyosarcoma is 48.4 years old (27-74 years).  It occurs more commonly in females (13 females, 7 males), and in the right pulmonary vein.

Leiomyosarcomas from either the pulmonary vein or the left atrium have similar morphological features consisting of highly cellular proliferations of spindle cells varying in size and shape, usually with bizarre pleomorphism.  Proliferative indices are high including mitotic rates ranging from 1-25 per 10 high power fields.  Regional necrosis is common.  The tumors tend to show immunoreactivity to desmin and actin, thereby confirming myogenous differentiation.  They fail to show epithelial, neural or vascular components by uniformly being negative for EMA, S100, CD34 and factor VIII.

The symptoms of pulmonary vein or left atrial leiomyosarcoma are non-specific and may include dyspnea, hemoptysis/bloody sputum, cough, chest pain, weight loss, ipsilateral pleural effusion, palpitations, paroxymal tachycardia and/or orthopnea.  Severe hemoptysis may necessitate blood transfusion.  Sometimes, occlusion of the right superior pulmonary vein may occur.

Since cardiac leiomyosarcomas preferentially arise in the left atrium as myxoid neoplasms, distinction from atrial myxoma may be difficult on a limited, pre-surgical biopsy.  It is therefore recommended to resect all atrial myxoid tumors with a wide (at least 1 cm) margin.

The diagnosis of pulmonary or cardiac leiomyosarcoma is frequently delayed because of the non-specific nature of the symptoms.  By the time of diagnosis, the tumor is usually large, showing invasion and/or metastasis.  The prognosis is generally poor with postoperative survivals of 6 months (75%), 1 year (73%), 2 years (50%) and 3 years (33%), respectively.  The current therapy of choice is early, complete surgical extirpation with post-operative chemotherapy being reserved for tumors which are incompletely removed.

Suggested Reading:

Gyhra AS, Santander CK, Alarcon EC, et al: Leiomyosarcoma of the pulmonary veins with extension to the left atrium. Ann Thorac Surg. 61:1840-1841, 1996.

Ko TM, Mayer DA, Tsapogas MJ Forbes A and Marchioro TL. Leiomyosarcoma of the pulmonary vein. J Cardiovasc Surg. 37(4):421-3, 1996.

Oliai BR, Taxelarr HD, Lloyd RV, et al: Leiomyosarcoma of the pulmonary veins. Am J Surg Pathol 23:1082-1088, 1999.

Laroia ST, Potti A, Rabbani M, Mehdi SA, Koch M. Unusual pulmonary lesions: case 3. Pulmonary vein leiomyosarcoma presenting as a left atrial mass. J Clin Oncol. 1;20(11):2749-51, 2002.

Gürbüz A, Yetkin U, Yilik L, Ozdemir T, Türk F. A case of leiomyosarcoma originating from pulmonary vein, occluding mitral inflow. Heart Lung. Heart lung. 32(3):210-4, 2003.

Khemichian S, Bemanian S. Pulmonary vein leiomyosarcoma. Intern Med J 36(12):793-4, 2006.

History: A 20-year-old woman presented with chronic jaw pain and swelling in the left cheek. Computerized tomography (CT) scan identified an expansile, multilocular, osteolytic mass in the left lower maxillary sinus (Fig. 1). The mass had lobulated margins and contained microcystic elements with a large cyst measuring 24 mm. The mass was completely excised which showed dark red fluid inside the cysts. Grossly, the lesion contained heterogeneous, reddish-brown friable soft tissue fragments intermixed with hard components. “January 2009: A 20 y.o. woman with an osteolytic cystic mass in the maxillary sinus”Continue reading