When the patient was 74 years old, she visited her GP due to swelling of the left lower limb, fatigue, and bruising (Table 1, Timeline Day 0). Her blood cell count showed remarkable anemia [hemoglobin (Hb): 8.8 g/dl] and thrombocytopenia [platelet (PLT) count: 25 x 109/L]. After a consultation with the HUH ER and hematologists, more laboratory tests, a whole-body CT scan, and a bone marrow biopsy were scheduled. The hypothesis of the hematologists included myelodysplastic syndrome (MDS).
A week after she visited her GP (before her CT scan and bone marrow biopsy), the patient was admitted to the HUH ER due to pain, worsening edema, and a bruise on her left lower limb. A clinical examination revealed a palpable mass in her abdomen and pain when flexing her left hip. The patient was afebrile and did not have a history of weight loss. She presented with worsening anemia (Hb: 8.0 g/dl), thrombocytopenia (PLT: 17 x 109/L), and elevated infection markers [white blood cells (WBC): 15.0 x 109/L; C-reactive protein (CRP): 39 mg/L]. Her blood electrolytes, sugar level, liver and kidney function, clotting time, vitamin B12, and folic acid tests were normal, but the ferritin level was elevated. Blood and urine samples were collected for bacterial cultures. A thromboembolic event was suspected, and the patient was started on tinzaparin.
A body CT (including pulmonary angiography) scan showed small areas of ground-glass opacity, predominantly on the right side of the patient (Figure 2C). PE was not evident but could not be definitely excluded. Her abdominal CT scan showed growth of the suspected pseudotumor (to 6 cm x 7.5 cm x 9 cm, Figure 2D) and fractures of the pubic bone and trochanter major. The spleen appeared normal in size. A day later, a lower-limb ultrasound (US) was performed, which ruled out the presence of DVT. Due to a further decrease in the patient's Hb and PLT levels and the need for RBC and PLT transfusions, treatment with tinzaparin was discontinued. The results of her blood and urine bacterial cultures and Helicobacter tests were negative. MDS, malignancy, or bleeding (e.g., hematoma of the psoas region) was suspected.
A bone marrow biopsy was performed, and its preliminary results showed negative for MDS, leukemia, lymphoma, and other malignancies. An abdominal CT scan with angiography was performed again, and no signs of bleeding were found. The radiology report indicated that her suspected pseudotumor was large, but there was no significant change in size compared with the scan taken 3 days earlier. The arthroplasty surgeon from the HUH Arthroplasty Center (HUS Peijas Hospital, Vantaa, Finland) was contacted for consultation. Metal artifact-reducing sequence magnetic resonance imaging (MARS-MRI) was recommended but was not immediately available.
A full blood count indicated reticulocytosis (150-310; normal range: 30-108 x 109/L), low RBC fragments (0.8%-1.1%), and elevated WBC with neutrophilia but normal-to-borderline-low lymphocytes. The patient's hemolysis markers (e.g., haptoglobin and bilirubin) and clotting times were normal. Her plasma protein fractions were normal except for borderline-low albumin levels. Lactate dehydrogenase (450-560 U/L; normal range: 155-255 U/L) and D-dimer (30-38 mg/L; normal range: <0.5 mg/ml) were elevated. A Coombs C3d test was positive. An iron panel showed mild iron deficiency and elevated erythropoietin (EPO) levels. Iron was administered intravenously to correct her iron deficiency. Thyroid hormone tests were normal. Paroxysmal nocturnal hemoglobinuria tests were negative. Based on her laboratory results, autoimmune hemolytic anemia (AIHA), cold AIHA, idiopathic thrombocytopenic purpura (ITP), AIHA combined with ITP, and chronic disseminated intravascular coagulation (DIC) were considered possible. A cold hemagglutinin test was negative. Given her possible ITP, the patient received 40 mg of dexamethasone daily for 4 days and IV immunoglobulin (IVIG; 1 mg/kg per day) twice, without a significant response. Because of her poor response to PLT transfusions, hematologists suggested a peripheral mechanism contributing to thrombocytopenia (e.g., bleeding, vasculitis, or another inflammatory reaction).
Further tests were performed, which resulted negative for hepatitis, parvovirus, Epstein-Barr virus, and human immunodeficiency virus. Among the blood coagulation factors, factors VIII and IX, as well as the active von Willebrandt factor (vWF) and vWF antigen, were slightly above the normal ranges. However, factor FVXIII was slightly below the normal range. These findings suggest a reactive response to possible bleeding. The results of the final bone marrow biopsy of the patient showed normal cell lines, normal granulopoiesis and erythropoiesis, and no signs of MDS, leukemia, lymphoma, or other malignancies. A gene test for BCR-ABL:which can diagnose certain hematologic malignancies:was negative. Her interleukin 2 receptor levels were not as high as expected in hemophagocytic lymphohistiocytosis. Her antiphospholipid antibodies were negative.
MARS-MRI of her left THA and suspected pseudotumor showed significant growth of the mass in multiple locations, namely, the iliopsoas region (7.1 cm x 6.6 cm x 8.9 cm, Figure 2E), posteromedial to the acetabulum (4.7 cm x 4.8 cm x 8.8 cm, Figure 2F), and near the fractured trochanter major (4.1 cm x 2.1 cm x 6.4 cm, Figure 2G). The blood metal ion levels of the patient were not increased [cobalt (Co) level was below 0.9 microg/L, and Cr level was below 0.6 microg/L]. An arthroplasty surgeon was contacted for consultation. Since her diagnosis remained unclear and the rapid growth of the suspected pseudotumor in association with MoP THA was very unusual, US-guided 1 cm trocar biopsies with histopathological diagnosis, bacterial samples, and a new pelvic CT scan were requested before a possible surgery.
In the following 5 weeks after the patient's hospital admission, her condition slowly deteriorated. She suffered from hemoptysis, bleeding from oral mucous membranes and gingiva, and melena. Her oxygen saturation (Sat) values decreased to 88%-92%, and her consciousness became impaired. She had tachycardia [pulse (p.): 100] and minor changes in her electrocardiogram (ECG; T-wave inversion in lead III). A catheter was inserted to treat her urinary retention. Her head CT scan showed white matter degeneration that was normal for her age. A chest CT scan showed a wide, diffuse alveolar hemorrhage, and the related radiology report recommended tests for vasculitis. A pelvic CT scan (Figure 2H) showed wide osteolysis and several fractures around the acetabular components, and the related radiology report suggested osteomyelitis or a THA-associated infection. Tests for vasculitis [e.g., anti-neutrophil cytoplasmic antibody (ANCA) and myeloperoxidase] were negative. Because of her poor response to PLT transfusions, the patient was tested for anti-human leukocyte antigen (HLA) class I antibodies. She developed a strong immune response. HLA-typed platelets were needed, which significantly delayed the trocar biopsies. WBC (23 x 109/L) and CRP (145 mg/L) levels were elevated. Although no infection was evident, treatment with cefuroxime was initiated.
US-guided 1 cm trocar biopsies were performed twice. They showed dense connective tissue, some macrophages pigmented with foreign material (likely metal), and necrotic debris, suggesting an inflammatory reaction but neither infection nor malignancy (Supplementary Figure S1). After the trocar biopsies, treatment with cefuroxime was replaced with piperacillin-tazobactam. Later on, daptomycin was added to her treatment regimen.
Hematologists were confident about the peripheral mechanism for anemia and thrombocytopenia (i.e., pseudotumor-associated bleeding, vasculitis, or another inflammatory reaction). Excision surgery of the suspected pseudotumor was advised and performed to preserve the patient's life.
First, the proximal part of an old anterior scar was incised, and the pelvic part of the suspected pseudotumor was visualized through an iliac window following the medial surface of the ilium. The suspected pseudotumor, along with its capsule, was detached from its margins, requiring it to be opened for safe removal. The femoral nerve and pelvic vessels remained intact. Then, another incision was made to an old posterior scar at the trochanter major. As had been suspected, based on preoperative imaging, the visualized trochanter major was previously fractured. After the capsule was opened and the joint was dislocated, the femoral head part of the endoprosthesis was removed. The femur was lifted anteriorly, and the posterior part of the suspected pseudotumor was detached and removed. Through an anterosuperior opening at the acetabular cup, anteromedial to the ilium, all the remaining suspected parts of the pseudotumor were detached and removed. The acetabular part of the endoprosthesis was found to have partly loosened and was removed, along with the cement and mesh between the bone and cement, without significant bone loss. Surgical drapes were soaked in saline with epinephrin and used for hemostasis of the acetabular region. Then, the remaining femoral part of the endoprosthesis was visualized and removed without fractures. The patient was left with a Girdlestone situation. After additional hemostasis of the acetabular region with TachoSil  Fibrin Sealant patches, hydrogen peroxide lavage was administered, a surgical drain was placed, and the wounds were closed in layers. After collecting bacterial, TB, and fungus samples, all excised tissues were sent for a pathological examination. Macroscopically, the tumor resembled a typical granulation-tissue pseudotumor with no signs of bleeding.
The surgical blood loss of the patient was estimated at 1.9 L. While under general anesthesia, she needed a high-dose infusion of norepinephrine for severe hypotension. Pulmonary bleeding was evident during her intubation. The patient was extubated successfully and transferred back to the intensive care unit. Bleeding from the surgical drain (0.8 L) continued during her first postoperative day but gradually subsided thereafter. The surgical drain was removed on the third postoperative day.
Despite the excision of the patient's THA and pseudotumor, as well as RBC and PLT transfusions, her anemia and thrombocytopenia persisted. Immediately after her surgery, her blood lactate levels increased to 9 mmol/L (normal levels: 0.5-2.2 mmol/L) but then normalized within 2 days. Her WBC increased to 45.5 x 109/L and her CRP to 306 mg/L. Despite respiratory support with a high-flow nasal cannula, the patient had objective dyspnea and severe hypoxia due to an alveolar hemorrhage [arterial oxygen tension (PaO2): 7.3-8.5 kPa; fraction of inspired oxygen (FiO2): 0.4-0.7]. She did not tolerate a non-invasive ventilation mask. She became somnolent at first and then agitated. For sedation, a dexmedetomidine infusion was administered. She experienced a paroxysm of atrial fibrillation. A norepinephrine infusion was administered for hypotension, while furosemide was administered for oliguria. The patient developed moderate kidney insufficiency. Treatment with piperacillin-tazobactam was replaced with meropenem, while daptomycin was continued. She was also administered IVIG and anti-D immunoglobulin.
The histopathological diagnosis of the surgical pseudotumor revealed highly malignant AS. Because of the very poor prognosis of the condition, intensive care was withheld. After the patient was transferred to palliative care, she died within 24 h of severe hypoxia due to alveolar hemorrhage (68 days after her GP had detected her anemia and thrombocytopenia).
The histopathological diagnosis of her autopsy specimen showed an AS with CD31-positive cells in the pseudotumor (Figures 3A,B), lungs (Figures 3C,D), and bone marrow (Figures 3E,F).
When the patient was 74 years old, upon hospital admission, a body CT scan showed ground-glass opacity areas in the lungs (arrow), and.