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2012 — March Case of the Month

Posted March 20, 2012

CLINICAL SUMMARY: Left pelvic soft tissue  

CAP Foundation March Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 28-year-old woman with a radiologically aggressive left pelvic soft tissue mass underwent a resection. An 11.0 x 8.0 x 7.9 cm pericolonic mass with a 14.5 cm segment of sigmoid colon, left adrenal gland, and segment VIII of liver were received. The colon was not involved. The liver and adrenal gland contained metastatic tumor. Immunohistochemistry showed that the tumor cells were desmin +, smooth muscle actin +, and KIT –.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 9, and is leiomyosarcoma.

Criteria for Diagnosis and Comments:
Sections show a spindle cell neoplasm with differing degrees of differentiation. In the better differentiated regions, the tumor cells display intersecting fascicles. They have abundant pink cytoplasm and blunt-ended or “cigar-shaped” nuclei. The nuclei are centrally located and mitotic figures are prominent. There is an associated small area of relatively normal smooth muscle. The largest part of the tumor is poorly differentiated with hypercellular foci whose cells have a high nuclear/cytoplasmic ratio. The nuclei have lost their central location, are hyperchromatic and pleomorphic, contain intranuclear inclusions and are mitotically active. Prominent vessels in a staghorn-like pattern are seen focally. The morphology and immunophenotype establish the diagnosis of leiomyosarcoma.

Leiomyosarcomas account for 5 – 10% of all soft tissue sarcomas. They are principally tumors of adult life, pediatric leiomyosarcomas being reported only rarely. The most common sites are the retroperitoneal space and abdominal cavity. They also occur in intraabdominal locations and infrequently in soft tissue of the extremities and trunk. About 2/3 of retroperitoneal leiomyosarcomas occur in women and the median age at presentation is 60 years. Abdominal pain and mass are the most frequent presenting symptom and sign, respectively. Liver is the most common site of metastasis, followed by lung and bone.

Grossly, the neoplasm typically presents with a gray, white or tan cut surface and irregular margins. The lesion usually contains large zones of necrosis, hemorrhage, and cystic degeneration. Histologically, leiomyosarcomas may display a spindle cell, epithelioid, myxoid, inflammatory, or granular cell morphology. Leiomyosarcomas are highly aggressive tumors, especially when arising in the retroperitoneum. The cause of death is due not only to distant metastasis but also due to local extension as it is often impossible to obtain total resection due to the tumor size. p53 mutation is identified in 50% of cases. However, the correlation between p53 mutation and prognosis is not linear. Immunohistochemical expression of smooth muscle actin (SMA) can be detected in most leiomyosarcomas. Desmin, another valuable marker for this tumor, can be detected in 50 – 100% of cases.

For leiomyosarcomas, strict criteria for malignancy are difficult to determine since smooth muscle tumors present as a biological continuum. Based on differentiation, cellularity, presence or absence of anaplasia, and mitoses, leiomyosarcomas are classified into 3 grades. Analysis showed that the 5-year survival rates for grade 2 – 3 tumors are less than 30%, whereas that for grade 1 is 75%. For all smooth muscle tumors, those with 0 – 5 mitoses per 50 HPF and without nuclear atypia are considered benign leiomyomas. If the mitotic count reaches 1 – 4 per 10 HPF, the tumors are better considered potentially malignant. For tumors with >5 mitoses per 10 HPF, malignancy is assumed. The present case has polymorphic nuclei and a mitotic count >5 per 10 HPF.

Extragastrointestinal stromal tumors comprise fewer than 5% of all gastrointestinal stromal tumors (GISTs). It is an adult tumor with only rare cases reported in children. . Approximately 80% of the tumors arise in the omentum and mesentery with remainder occurring in the retroperitoneal space. GISTs can display either spindle or epithelioid morphology. The most common histological presentation is that of a spindle cell tumor with moderate to slight interstitial collagen. 20 – 30% of GISTs are malignant and may histologically resemble leiomyosarcoma. These former tumors usually have less eosinophilic cytoplasm and minimal nuclear pleomorphism although some malignant GISTs can have considerable nuclear pleomorphism. Virtually all GISTs are strongly and uniformly KIT positive. Approximately 60 – 70% are also positive for CD34.

Fibrosarcomas have become vanishingly rare over the last 2 decades with the further classification of malignant spindle cell tumors and are most common at 30 – 55 years of age. The most common sites are in the deep soft tissues of the lower extremities, followed by the upper extremities and trunk. Grossly, the tumors display gray-white to tan-yellow coloring on sectioned surfaces, which are soft to firm, fleshy, and either round or lobulated. Histologically, the tumor cells display a herringbone type pattern. The cells are uniformly spindle shaped with scanty cytoplasm and indistinct cell borders. Immunohistochemically, the cells stain strongly and diffusely for vimentin, focally and weakly for muscle-specific actin and smooth muscle actin in a subset of cases and are negative for epithelial antigens.

Synovial sarcoma is most prevalent in adolescents and young adults (15 – 40 years). It occurs predominantly in the extremities. About 5 – 10% of synovial sarcomas arise in the trunk. Histologically, the tumor cells are stereotypically composed of two morphologically different cell types that form a characteristic biphasic pattern; epithelial cells and spindle cells. Most synovial sarcomas display immunoreactivity for cytokeratins and epithelial membrane antigen. CD99 can be detected in 60 – 70% of cases and bcl-2 in 75 – 100% of cases in a strong and diffuse fashion. A specific translocation, t(X;18) containing one of several fused products, most principally SYT/SSX can be detected either by FISH or RT-PCR in more than 90% of cases.

Malignant peripheral nerve sheath tumors (MPNSTs) account for 5 – 10% of soft tissue sarcomas. Most tumors occur in 20 – 50-year-olds. About 1/4 to 1/2 occur in association with neurofibromatosis 1. Most MPNSTs arise in sites with major nerve trunks, such as in proximity to the sciatic nerve, brachial plexus, and sacral plexus. The cells of MPNSTs are arranged in irregular sweeping fascicles. The nuclei of MPNSTs’ cells are “wavy,” buckled or comma-shaped, and the cytoplasm is lightly stained and usually indistinct. Approximately 50 – 90% of MPNSTs are immunoreactive to anti-S100 protein and immunoreactivity to other neural markers varies widely.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which of the following lesions is not immunoreactive to epithelial antigens? A. Fibrosarcoma
B. Leiomyosarcoma
C. Malignant peripheral nerve sheath tumors
D. Synovial sarcoma
2. All of the following typically show KIT positivity on immunohistochemistry EXCEPT: A. Gastrointestinal stromal tumor
B. Leiomyosarcoma
C. Melanoma
D. Seminoma
3. The translocation t(X;18) is specific for which tumor? A. Fibrosarcoma
B. Gastrointestinal stromal tumor
C. Leiomyosarcoma
D. Synovial sarcoma

References

  1. Abraham SC. Distinguishing gastrointestinal stromal tumors from their mimics: An update. Adv Anat Pathol. 2007;4:178-88.
  2. de Alava E. Molecular pathology in sarcomas. Clin Transl Oncol. 2007;9:130-144.
  3. Katz SC, DeMatteo RP. Gastrointestinal stromal tumors and leiomyosarcomas. J Surg Oncol. 2008;97:350-359.
  4. Raut CP, Pisters PW. Retroperitoneal sarcomas: Combined-modality treatment approaches. J Surg Oncol. 2006;94:81-87.
  5. Skubitz KM, D’Adamo DR. Sarcoma. Mayo Clin Proc. 2007;82:1409-1432.
  6. Wang VY, Potts M, Chou D. Sarcoma and the spinal column. Neurosurg Clin N Am. 2008;19:71-80.

Author:
2009
Shuting Bai, MD, PhD
University of Alabama at Birmingham
Birmingham, AL

Gene P. Siegal, MD, PhD FCAP
Surgical Pathology Committee
University of Alabama at Birmingham
Birmingham, AL