BACKGROUND: Recipient\'s high resolution HLA typing is required in allogeneic hematopoietic cell transplantation from unrelated donors, as well as for haploidentical family donors. For these purposes, Next-Generation Sequencing (NGS) methods are the gold standard.
METHODS: We present a case of a patient with an incorrect HLA typing result caused by the population of circulating lymphoma cells. The first HLA examination was performed from peripheral blood (PB) using NGS in the active phase of diffuse large B-cell lymphoma with bone marrow involvement.
RESULTS: Because of rare and inconclusive results, confirmed twice for the A* locus (A*02:32N), real-time polymerase chain reaction (RT-PCR)was performed. With RT-PCR method, we obtained more expected results according to the population allele frequency: in HLA-A locus (A*02:01) but also in DQB1 (DQB1*03:01, not as in NGS - DQB1*03:10). For the final verification, we used swab material and we obtained unambiguous NGS result with expected, frequent HLA-A*02:01 and DQB1*03:01 alleles corresponding to the RT-PCR result from PB.
CONCLUSIONS: To conclude, we suspect that the discrepancies between NGS and RT-PCR results were caused by the presence of a significant amount of circulating lymphoma cells in the peripheral blood sample. Lymphomagenic mutations may involve the histocompatibility antigen coding region and affect HLA expressed on malignant cells. This finding may be relevant for the selection of test material in primary and confirmatory HLA testing in patients with active hematological malignancies because of the strong impact of incorrect HLA typing on the procedure of a donor selection.

BACKGROUND: Acute tumour embolism to the popliteal artery resulting in limb-threatening ischemia is a rare complication of neoplastic disease. Generally, tumors embolize to the pulmonary circulation via the venous system. In this case, the originating tumor was a lung cancer of a large size and advanced stage that had invaded the left atrium of the heart and disseminated in the systemic circulation. The tumor likely fragmented, resulting in showering to the right popliteal artery, superior mesenteric artery, and left renal artery, which is a unique presentation of tumor embolism.
METHODS: We present a case of a 62-year-old Caucasian gentleman with a large left lower lobe squamous cell lung cancer that had invaded into the left atrium via the pulmonary veins. He presented with acute limb threatening ischemia. A computed tomographic angiogram revealed an occlusion of the left popliteal artery as well as embolization to the superior mesenteric artery and the right renal artery. He was started on intravenous heparin and underwent an emergency popliteal embolectomy and calf fasciotomies, which was limb saving. His fasciotomy wounds were closed after 1 week and he was discharged on anticoagulation.
CONCLUSIONS: This is a rare case of tumor embolism resulting in both an embolectomy and calf fasciotomies. In the light of such cases, we suggest that tumors invading the bloodstream should be considered high risk for embolization and hypothesize that prophylactic antithrombotic therapy may avoid major morbidity.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare entity with poor prognosis, and often diagnosed postmortem. PTTM is resulting from tumor emboli induced activation of coagulation cascade, fibrin clot formation and fibrocellular intimal proliferation in pulmonary microvasculature.
METHODS: The patient was a 65-year-old female, with past medical history of ovarian high-grade serous carcinoma, presented with chest pain and shortness of breath. The chest computed tomography (CT) revealed innumerable new lung nodules as well as small hazy and patchy opacities compared to the chest CT 2 months before current presentation. She developed progressive respiratory failure and expired. A lung-restricted autopsy showed diffuse subcentimetric nodules in bilateral lungs grossly. Microscopic examination revealed the lung parenchyma demonstrated numerous tumor emboli consisting of pleomorphic tumor cells with varying degrees of fibrin deposition and fibrocellular intimal proliferation in the pulmonary arterioles, small arteries, and capillaries in the alveolar septa. Immunohistochemistry confirmed the ovarian origin of the tumor cells. The findings were consistent with PTTM secondary to metastasis of ovarian high-grade serous carcinoma. Literature review of PTTM caused by ovarian cancer was conducted.
CONCLUSIONS: PTTM is a fatal entity with rare association with primary ovarian malignancy. This case study demonstrates the clinicopathological features of PTTM associated with high-grade serous carcinoma, and it will be the second case of PTTM with this association in the literature.

OBJECTIVE: Herein, we report a case of a patient with recurrent breast cancer who was diagnosed antemortem with pulmonary tumor thrombotic microangiopathy (PTTM) using wedge aspiration cytology of the pulmonary artery after breast cancer surgery.
METHODS: The patient was a 50-year-old woman who underwent mastectomy and axillary lymph node dissection for stage IIIA (T3N2M0) triple-negative left breast cancer. Postoperative follow-up was performed with radiotherapy and anticancer chemotherapy. Seventeen months after the surgery, the patient was hospitalized for right heart failure and diagnosed with pulmonary arterial hypertension. The patient was diagnosed with PTTM following the detection of malignant cells in the pulmonary artery using wedge aspiration cytology. Anti-pulmonary hypertension therapy was administered; however, the patient did not respond and died 26 days after admission. Autopsy revealed multiple microscopic tumor emboli in the pulmonary artery. In portions of the pulmonary artery without embolization, fibro-cellular intimal hyperplasia and stenosis were observed. Tumor embolism was expressed for CK7+/CK20-, consistent with the primary breast cancer.
CONCLUSIONS: Since the primary pathophysiology of PTTM entails narrowing due to fibro-cellular intimal hyperplasia rather than multiple tumor thrombi, the efficacy of chemotherapy combined with vasodilators is discussed.

A 77-year-old man was admitted at our hospital due to \"generalized increase in the number of masses and enlargement of the masses observed for one month\". Combined assessment of the imaging (computed tomography and magnetic resonance imaging) findings and results of lung centesis biopsy and liquid biopsy suggest that the patient had small cell lung cancer of the left upper lobe, with right hilar, mediastinal, bilateral axillary, abdominal and retroperitoneal lymph node metastases, as well as widespread subcutaneous soft tissue, liver, bilateral adrenal, bilateral kidneys and multiple brain metastases (extensive stage). In order to obtain an evaluation of the development of the disease as soon as possible, the circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) in 6 mL peripheral blood were examined by subtraction enrichment-immunostaining fluorescence in situ hybridization (SE-iFISH) technology. A total of 919 epithelial cell adhesion molecule (EpCAM)-positive CTCs and 61 EpCAM-positive CTM were identified. Among them, there were 14 haploid CTCs (1.52%), 788 diploid CTCs (85.75%), 44 triploid CTCs (4.79%), 70 tetraploid CTCs (7.62%) and 3 pentaploid or higher-fold polyploid CTCs (0.33%). Herein, we reported a rare case with extremely high accounts of CTCs and CTM and positive findings for tumor markers, which was identified for the first time. The examination of CTCs by SE-iFISH contributed to the diagnosis, prognosis and treatment evaluation of cancer and facilitated the formulation of precise and individualized therapeutic regime.

Pulmonary tumor embolism (PTE) and pulmonary tumor thrombotic microangiopathy (PTTM) are rare etiologies for rapidly progressive dyspnea in the setting of undiagnosed metastatic cancer. They occur most frequently in association with adenocarcinomas, with PTE being most frequently associated with hepatocellular carcinoma and PTTM being most commonly reported with gastric adenocarcinoma. Pulmonary tumor embolism and PTTM appear to be a disease spectrum where PTTM represents an advanced form of PTE. Pulmonary tumor embolism and PTTM are mostly identified postmortem during autopsy as the antemortem diagnosis remains a clinical challenge due to the rapidly progressive nature of these rare diseases. We report 2 cases of rapidly progressive respiratory failure leading to death, due to tumoral pulmonary hypertension resulting from PTE and PTTM, diagnosed postmortem. Both of the patients were middle-aged females, nonsmokers, and had a gastrointestinal source of their primary malignancy.

Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female.
51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma.
An early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms.

UNASSIGNED: Renal cell carcinoma is one common type of urologic cancers. It has tendencies to invade into the inferior vena cava (IVC) and usually requires an open surgery procedure. High rates of operative complications and mortality are usually associated with an open surgery procedure. The recently emerged robot-assisted laparoscopic radical nephrectomy (RAL-RN) and IVC tumor thrombectomy have shown to reduce operative related complications in patients with renal cell carcinoma.This case series study aimed to summarize technical utilization, perioperative outcomes, and efficacies of RAL-RN and IVC tumor thrombectomy in our hospital. A retrospective analysis was performed on clinical data from 20 patients who underwent RAL-RN and IVC tumor thrombectomy from January 2017 to December 2019 in our department.Patients had a median age of 59 years (interquartile range [IQR], 46-68). Four patients had renal neoplasm on left side and 16 on right side. Nineteen patients underwent RAL-RN (level 0: n = 2) or RAL-RN with IVC thrombectomy (n = 17) (level I: n = 3; level II: n = 12; and level III: n = 3) and 1 patient was converted into an open surgery. The median operative time was 328 minutes (IQR, 221-453). The estimated median blood loss was 500 mL (IQR, 200-1200). The median size of removed renal carcinoma was 67 cm2 (IQR, 40-91); the length of IVC tumor thrombus was 5 cm (IQR, 3-7). The postsurgery hospital length of stay was 6 days (IQR, 5-7). The complications included intestinal obstruction (n = 1), lymphatic fistula (n = 1), heart failure (n = 1), and low hemoglobin level (n = 1). The outcomes for patients after 16 months (IQR, 11-21) follow-up were tumor-free (n = 10), tumor progression (n = 4), loss of contact (n = 1), and death (n = 5).We concluded that RAL-RN and IVC thrombectomy renders good safety profiles including minimal invasiveness, low estimated median blood loss, short hospitalization, low morbidity, and quick renal function recovery. The long-term efficacy needs a further investigation.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer worldwide, however, its metastatic spreading is extremely rare.
METHODS: We present a case of advanced BCC with rapid growth of new tumor lesions in a patient who was later diagnosed with Gorlin syndrome. Due to the advanced disease stage, the patient was examined for circulating tumor cells (CTCs), which are used as a prognostic marker in some metastatic malignancies. To date, no studies have been found that could assess the BCC tumor and the presence of CTCs in peripheral blood. CTCs were obtained after each surgical excision and during systemic oncological therapy from the peripheral venous blood by size-based isolation method (Metacell®) and cultured in vitro for 7 days. CTCs were enriched by size-based separation and examined using vital fluorescence microscopy. Cytomorphological comparison of CTCs with cells from the tumor lesions was provided. In the course of the treatment, the CTCs count in the blood decreased after surgical removal of the tumorous mass, but finally, the sustained and persisting decrease in CTCs was achieved with a hedgehog pathway inhibitor treatment.
CONCLUSIONS: The detection of CTCs points a systematic disease behavior in this case.

Involvement of serous cavity specimens by alveolar rhabdomyosarcoma (ARMS) is a rare event and only a few case reports have been reported in the literature, with conflicting cytomorphologic patterns. Herein, we report on a 41-year-old man with no significant past medical history who presented with pancytopenia and shortness of breath and was found to have widely metastatic sinonasal alveolar rhabdomyosarcoma, including involvement of the pleura. The pleural fluid specimen was cellular and contained ARMS cells in small-to-medium sized three-dimensional fragments that resembled an adenocarcinoma or mesothelioma, and numerous single cells were seen in the background. The individual tumor cells demonstrated variable morphology; all were large, with varying degree of cytoplasm, and multinucleated cells were commonly seen in the background. The cells were negative for calretinin and claudin-4 and were positive for myogenin, confirming the diagnosis. Given the cytomorphologic diversity of ARMS seen in serous fluid specimens, patient history and the use of confirmatory immunostains are essential.