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A 75-year-old woman with constitutional symptoms, precipitous functional decline
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A 75-year-old woman with a medical history significant for obesity, diabetes mellitus type 2 and coronary artery disease presented with a 6-month history of constitutional symptoms, multiple hospitalizations for dehydration and electrolyte imbalances, and a precipitous functional decline. She was noted on several occasions to have a marked leukocytosis and was treated with various antibiotic regimens without a known infectious source. A CT scan of the chest/abdomen/pelvis revealed what was thought to be an enlarged inguinal lymph node (Figure 1).
She underwent CT-guided biopsy of the inguinal lymph node which was concerning for malignancy and she was referred to medical oncology at our tertiary facility for work-up of presumed lymphoma. On presentation, she had a leukocytosis of 70.8 x 109/L. PET/CT revealed avid uptake in the inguinal mass, diffuse marrow uptake and an enlarged spleen.
Figure 2. MRI with axial T2 gadolinium contrast image demonstrates a heterogeneous mass with mild contrast enhancement and areas of central necrosis consistent with soft tissue sarcoma.
Source: Peter S. Rose, MD
In the next step in diagnosis, we reviewed with hematology and the decision was made to proceed with bone marrow biopsy to better evaluate a suspected myeloproliferative disorder. Biopsy revealed granulocytic hyperplasia with prominent neutrophilia and negative cytogenetic, FISH and molecular analysis suggesting leukemoid reaction. Outside pathology slides from the inguinal mass biopsy were reviewed and read as high-grade sarcoma without any evidence of lymph node elements. MRI of the pelvis was obtained and demonstrated a heterogeneous mass with areas of central necrosis consistent with sarcoma (Figure 2). There was no evidence of metastatic disease on review of the PET/CT.
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Paraneoplastic leukocytosis secondary to soft tissue sarcoma
Given the patient’s waning clinical status, the decision was made to proceed with wide resection with plans for adjuvant radiotherapy. A 7.5 x 7.2 x 5.2-cm soft tissue mass was excised and sent for pathologic review; histology was consistent with epithelioid myxofibrosarcoma, completely excised and all margins were negative (Figure 3). The patient’s preoperative white blood cell count (WBC; drawn the morning of surgery) was 72.6 x 109/L. Within 7 hours of resection, this had decreased to 52.6 x 109/L. Postoperative day 1, the WBC further diminished by more than half to 19.6 x 109/L. This decline continued each day, reaching 9.3 x 109/L by postoperative day 4; a value within the normal expected range at our institution. By the time of discharge on postoperative day 7, the WBC was 5.6 x 109/L (Figure 4). Of note, the patient’s constitutional symptoms also quickly resolved; she repeatedly reported her markedly improved appetite and stamina in the days following tumor resection.
Apart from wound complications requiring an irrigation and debridement and wound vac therapy, she did well the first few months following surgery. The patient was informed that data concerning her case would be submitted for publication and she agreed. Unfortunately, at 6 months post resection, she was diagnosed with widespread metastatic disease. This was refractory to systemic chemotherapy and she ultimately deceased approximately 1 year from her primary tumor resection.
Figure 4. Graphic illustration shows the patient’s WBC count in the days leading up to and following sarcoma resection.
Reports of paraneoplastic leukocytosis associated with soft tissue sarcoma are rare. All identified cases were associated with either disseminated disease or the inflammatory variant of undifferentiated pleomorphic sarcoma. This phenomenon is not entirely understood; however, multiple reports have identified elevated levels of G-CSF and other proinflammatory cytokines in the serum of patients at presentation. Hocking and colleagues demonstrated production of granulocyte-colony stimulating factor (G-CSF) by rhabdomyosarcoma tumor cells in-vitro. As in our case, others have reported resolution of leukocytosis with tumor resection. Collectively, these findings suggest that the bone marrow proliferation and maturation observed in this phenomenon is in direct response to tumor-derived inflammatory cytokines. In their review of the inflammatory variant of undifferentiated pleomorphic sarcoma, Hurtado-Cordovi and colleagues noted that patients with elevation of the WBC beyond 100 x 109/L could not tolerate chemoradiation and that this finding heralded rapid clinical deterioration. This stresses the importance of early detection and proper treatment of the underlying malignancy.
As in the case presented here, paraneoplastic leukocytosis is often mistaken for leukemia or another myeloid neoplasia, leading to unnecessary testing and delays in definitive diagnosis and treatment. To our knowledge, this is the first report of leukemoid reaction secondary to a localized epithelioid myxofibrosarcoma. Awareness of the association between paraneoplastic leukocytosis and appendicular soft tissue sarcomas can lead to the avoidance of unnecessary testing and delays in diagnosis, thus facilitating more rapid initiation of proper definitive treatment.
- References:
- Hisaoka M, et al. Pathol Int. 1997;47:642-646.
- Hocking W, et al. Blood. 1983;61:600-603.
- Hurtado-Cordovi J, et al. ISRN Oncol. 2012;doi:10.5402/2012/946019.
- Nara T, et al. Br J Dermatol. 2003;doi:10.1111/j.1365-2133.2003.05684.x.
- Sonobe H, et al. Hum Pathol. 1997;doi:10.1016/s0046-8177(97)90236-7.
- Van Arendonk KJ, et al. JAMA Surg. 2016;doi:10.1001/jamasurg.2016.3180.
- Yang T, et al. Am J Clin Pathol. 2013;140:A238.
- For more information:
- Douglas W. Bartels, MD; Bayard C. Carlson, MD; Joshua D. Johnson, MD; and Peter S. Rose, MD, can be reached at Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Bartels’s email: bartels.douglas@mayo.edu. Carlson’s email: carlson.bayard@mayo.edu. Johnson’s email: johnson.joshua3@mayo.edu. Rose’s email: rose.peter@mayo.edu.
- Edited by Joshua D. Johnson, MD, and Nicholas A. Trasolini, MD. Johnson is a chief resident in the department of orthopedic surgery at Mayo Clinic in Rochester, Minnesota. He will be a musculoskeletal oncology fellow at MD Anderson following residency. Trasolini is the administrative chief resident in the department of orthopedic surgery at Keck Medical Center of the University of Southern California and will be a sports medicine fellow at Rush University Medical Center following residency. For information on submitting Orthopedics Today Grand Rounds cases, please email: orthopedics@healio.com.
Disclosures: Bartels, Carlson, Johnson and Rose report no relevant financial disclosures.