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Synchronous Bone Marrow Metastasis from Primary Splenic Angiosarcoma To the Editor: Metastasis is an early and frequent phenomenon in primary splenic angiosarcoma, with reported incidence ranging from 69 to 86 per cent of patients. The most common sites of metastasis are liver, lung, lymph nodes, and bone.1 Bone marrow (BM) metastasis, however, is exceedingly rare. Synchronous BM metastasis is even rarer, with only two prior descriptions in the literature.2 We believe that ours is the first patient from the United States to be described with this rare presentation. A 57-year-old woman with a past medical history of a resected ovarian dysgerminoma was referred to our institution for several weeks of left-sided abdominal pain and fullness. She denied fevers, B-symptoms, nausea, vomiting, or unintentional weight loss. She had no history of prior chemoradiation. Recent mammogram and colonoscopy were normal. There was no known contributory family history. Physical exam was remarkable for massive splenomegaly, palpated 10 cm below the left subcostal margin, and moderate left upper quadrant (LUQ) tenderness. An extensive laboratory evaluation revealed microcytic iron-deficiency anemia with schistocytes on peripheral smear, suggestive of endothelial damage. Given her splenomegaly and abnormal hematologic workup, a BM aspiration and biopsy was performed. It demonstrated trilineage hematopoiesis, and atypical vascular proliferation with mitotically active cells that had irregular nuclear contours. Immunohistochemical staining with CD34, CD31, and factor VIII-related antigen highlighted clusters of atypical endothelial cells forming vascular channels. Taken together, these
Address correspondence and reprint requests to Nipun B. Merchant, M.D., Department of Surgery, Vanderbilt University Medical Center, 2220 Pierce Avenue, 597 Preston Research Building, Nashville, TN 37232. E-mail:
[email protected].
findings were highly suspicious for BM involvement by angiosarcoma. A computed tomographic scan of the abdomen showed a diffusely enlarged and nodular spleen measuring 22 cm in greatest dimension (Fig. 1A). There was also evidence of left hydronephrosis, possibly from splenic mass effect. There was no evidence of mesenteric lymphadenopathy or metastatic disease. A positron emission tomography scan demonstrated increased Fludeoxyglucose (FDG) uptake in the spleen without any other significant FDG avid lesions (Fig. 1B). Given the requirement for definitive tissue diagnosis, patient’s LUQ tenderness, obstructive hydronephrosis, and risk for spontaneous splenic rupture, we proceeded with exploratory laparotomy and splenectomy. Upon entry into the abdomen, an extremely large and nodular spleen was noted extending down to the umbilicus. Extensive peri-splenic adhesions to the retroperitoneum, left lateral segment of the liver, and diaphragm were lysed. After complete mobilization, the massive spleen was removed with considerable difficulty from the wound. Gross inspection of the
FIG. 1. Radiographic evidence of splenic angiosarcoma. A Representative section from abdominal CT scan showing diffusely enlarged spleen with irregular and heterogeneous hyperattenuating densities; B PET scan showing increased heterogeneous FDG uptake in a significantly enlarged spleen.
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resected specimen revealed a 2052 gram spleen with an 8 · 8 cm irregularly defined, firm yellow-tan mass abutting the splenic capsule. Microscopic analysis of this region revealed an infiltrating vascular neoplasm with extensive necrosis (> 50%), numerous atypical mitotic figures, and anastomosing vascular channels. Tumor cells were diffusely positive for CD34 and CD31, and focally positive for factor VIII-related antigen. Based on these findings, the tumor was diagnosed as high-grade angiosarcoma of the spleen. The patient had an uneventful hospital course and was discharged home on postoperative day 3. Since discharge, a magnetic resonance imaging scan demonstrated diffuse marrow replacement throughout the anterior and posterior elements of the lumbar spine. The marrow displayed heterogeneous contrast enhancement, likely due to diffuse metastatic infiltration (Fig. 2). The patient has declined palliative systemic chemotherapy. Primary splenic angiosarcoma is rare (0.14–0.25 per million), but is the most common nonhematolymphoid malignancy of the spleen. Patients most commonly present with LUQ pain and splenomegaly (68–83%). Anemia and thrombocytopenia are found in up to 81 per cent and 55 per cent of patients, respectively.1 CT often reveals nodular masses of heterogeneous low attenuation in a large spleen. Due to the risk of spontaneous rupture and subsequent hemoperitoneum, percutaneous needle biopsy
FIG. 2. MRI of spine with contrast showing diffusely abnormal marrow signal representing metastatic involvement of lumbar spinal marrow.
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for tissue diagnosis is generally avoided. Histological diagnosis, therefore, is preferably made after splenectomy. In many instances, as in this case, splenectomy is also performed for symptomatic relief or splenic mass effect. On histological examination, foci of necrosis, atypical mitotic activity, and infiltrating growth may distinguish malignant from benign vascular tumors.1 In fact, 5-year disease-free survival has been shown to be better in low-grade primary lesions.3 Adjuvant therapies are typically reserved for metastatic or inoperable disease. Due to its rarity, specific chemotherapeutic regimens have not been well studied in prospective trials for splenic angiosarcoma. Recently, a phase II clinical trial showed that weekly paclitaxel was well tolerated and demonstrated clinical benefit in angiosarcoma. There is also growing interest in the use of other antiangiogenic agents to target angiosarcoma.3 However, despite best efforts, the prognosis for this diagnosis is poor with mean survival ranging from 10.3 to 14.4 months.1 Early metastasis from splenic angiosarcoma largely contributes to this grim prognosis. Up to 86 per cent of patients have distant metastases at the time of presentation. BM metastasis, however, is exceptionally rare. Interestingly, Wang et al.2 have suggested that angiosarcomas arising in the spleen have a unique propensity for BM metastasis. Our report seems to strengthen that argument. In fact, the true incidence of BM metastasis might actually be underreported because 1) BM biopsy is not routinely performed on patients with systemic metastasis, and 2) occult BM metastasis may not readily be detected on routine imaging studies. Because BM biopsy is a relatively sensitive technique for detecting metastatic marrow involvement despite the small volume of tissue sampled, it may be reasonable to consider BM biopsies for appropriate staging of patients with splenic angiosarcoma. This report also underscores the value of BM biopsy in assessing for metastasis even if the workup does not reveal a classic myelophthisic hematological picture. Although our patient had biopsy-proven BM metastasis, it is possible that the degree of BM infiltration was not critical enough to generate the distortion necessary for a myelophthisic cytopenia to develop. Instead, she presented with iron-deficiency anemia. This has previously been reported, with the etiology attributed to abnormal iron sequestration in a tumor-infiltrated spleen.4 Our patient’s anemia was more likely multifactorial; splenic sequestration of erythroid elements, myelophthisis, bleeding, hemolysis, and tumor-associated factors were likely contributory. Nevertheless, a low threshold for BM procedures should be maintained if any cytopenia exists in a patient with primary splenic angiosarcoma.
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THE AMERICAN SURGEON
Jashodeep Datta, M.D. School of Medicine Vanderbilt University Medical Center Nashville, Tennessee Tania Zuluaga Toro, M.D. Department of Pathology Vanderbilt University Medical Center Nashville, Tennessee Vicki L. Keedy, M.D. Department of Medicine Vanderbilt University Medical Center Nashville, Tennessee
September 2010
Vol. 76
Nipun B. Merchant, M.D. Department of Surgery Vanderbilt University Medical Center Nashville, Tennessee REFERENCES
1. Neuhauser TS, Derringer GA, Thompson LD, et al. Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases. Mod Pathol 2000;13:978–87. 2. Wang C, Rabah R, Blackstein M, et al. Bone marrow metastasis of angiosarcoma. Pathol Res Pract 2004;200:551–5. 3. Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma. J Clin Oncol 2008;26:5269–74. 4. Thomas JP, Porcell A, Sagone AL. Splenic angiosarcoma and iron deficiency anemia in a 43-year-old man. South Med J 2001;94:640–3.
