Fatal peripheral T-cell lymphoma presenting as hypereosinophilia and spontaneous tumor lysis syndrome: A rare case report
Majed B Momin1, Abhijeet Ingle1, G Vamshi Krishna Reddy2, Anamika Aluri2, B Saroj Kumar Prusty3
1 Department of Pathology, Yashoda Hospitals, Malakpet, Hyderabad, Telangana, India
2 Department of Medical Oncology, Yashoda Hospitals, Malakpet, Hyderabad, Telangana, India
3 Department of Critical Care Medicine, Yashoda Hospitals, Malakpet, Hyderabad, Telangana, India
|Date of Web Publication||6-Mar-2018|
Source of Support: None, Conflict of Interest: None
Peripheral T-cell lymphomas (TCLs) are a heterogeneous group of aggressive, uncommon forms of T-cell or natural killer cell-derived non-Hodgkin’s lymphomas. Acute tumor lysis syndrome (TLS) is a multiple metabolic derangement that occurs due to the treatment of malignancies or spontaneous tumor cell death. We report the case of a 56-year-old male patient who presented with marked eosinophilic leukocytosis, rash, and lymphadenopathy at the initial visit but finally manifested with TCL and spontaneous TLS. On the first visit, hemogram showed a marked eosinophilic leukocytosis and raised lactate dehydrogenase. The patient refused for admission; however, lymph node biopsy was done on day-care basis. After 3 days, the patient presented in the emergency room with shortness of breath, altered renal and liver parameters, and dyselectrolytemia. Based on histopathological with immunohistochemistry findings on lymph node biopsy and clinical and laboratory finding, the patient was diagnosed as TCL-not otherwise specified with TLS.
Keywords: Hypereosinophilia, peripheral T-cell lymphoma, tumor lysis syndrome
|How to cite this article:
Momin MB, Ingle A, Krishna Reddy G V, Aluri A, Kumar Prusty B S. Fatal peripheral T-cell lymphoma presenting as hypereosinophilia and spontaneous tumor lysis syndrome: A rare case report. Indian J Allergy Asthma Immunol 2018;32:34-8
|How to cite this URL:
Momin MB, Ingle A, Krishna Reddy G V, Aluri A, Kumar Prusty B S. Fatal peripheral T-cell lymphoma presenting as hypereosinophilia and spontaneous tumor lysis syndrome: A rare case report. Indian J Allergy Asthma Immunol [serial online] 2018 [cited 2018 Jun 7];32:34-8. Available from: http://www.ijaai.in/text.asp?2018/32/1/34/226696
Non-Hodgkin’s lymphoma (NHL) is a diverse group of lymphoproliferative cancers, of which peripheral T-cell lymphoma (PTCL) accounts for approximately 10% of all cases. PTCLs are a heterogeneous category of nodal and extranodal mature TCLs which do not correspond to any of the specifically defined entities of mature TCL in the current classification. The World Health Organization (WHO) classification system recognizes the subtypes of PTCL and has grouped the diseases into three categories: nodal, extranodal, and leukemic. WHO has also divided TCLs into two groups: aggressive (fast growing) and indolent (slow growing). PTCLs are rare in the United States and are more common in Asia, Africa, and the Caribbean, possibly due to exposure to specific viruses, such as the Epstein–Barr virus and the human T-cell leukemia virus-1.
Hypereosinophilia is a phenomenon which is associated with a broad variety of allergic, infectious, paraneoplastic, and systemic diseases. Depending on the etiology, these disorders differ in severity from self-limiting to life threatening. However, it is well known that hypereosinophilia can occur in association with hematolymphoid malignancies and a solid tumor.
Tumor lysis syndrome (TLS) is an oncological emergency that requires urgent medical attention and resuscitation to prevent life-threatening complications resulting from rapid lysis and breakdown of large-volume, aggressive tumors when chemotherapy is commenced or spontaneous tumor cell death. When the syndrome is seen before the institution of therapy, it is termed spontaneous TLS.
A 56-year-old male patient came to the outpatient Oncology Department of Yashoda Hospital, Malakpet branch, Hyderabad, for the evaluation of cervical swellings, abdominal discomfort, and an erythematous skin lesion on his back with itching all over the body. He noticed neck swelling 2 months ago followed by abdominal distension and itching with erythematous lesions since 8 days and history of fever for 3 days. On examination, the patient had maculopapular rash over the back [Figure 1], bilateral cervical and right inguinal lymphadenopathy, moderate ascites, and decreased air entry on both sides of the chest. He denied a history of allergy, including drug or food allergy. Moreover, he had no medical history of major illness or medication. His initial investigation reveals hemogram with marked eosinophilic leukocytosis (white blood cells: 2.10 lakhs/cumm) with eosinophils 90%, polymorphs 4%, lymphocytes 5%, and monocytes 1%. Peripheral smear morphology shows normocytic normochromic red blood cells. Marked eosinophilia with many enlarged eosinophils with trilobed forms was seen [Figure 2]. Few plasmacytoid lymphocytes were seen. There were no blast cells in the peripheral smear. Liver function test (LFT), kidney function test (KFT), and electrolytes were normal. A marked increase in lactate dehydrogenase (LDH) (6523 IU/L) was noted. Chest X-ray shows minimal effusion, while ultrasound abdomen reveals mild ascites and mild hepatosplenomegaly. Further, bone marrow aspiration and lymph node biopsy were performed on day-care basis as the patient was not willing for admission [Figure 1] and [Figure 2].
After 3 days, the patient presented to the emergency room with severe shortness of breath, decreased urine output, and drowsiness. Vital parameters show hypotension (70/50 mm of Hg), respiratory distress, and tachycardia (110 beats/min). Ionotropic support and noninvasive ventilation support were started. Investigations were done which revealed abnormal KFT, LFT, and dyselectrolytemia as compared to the previous laboratory reports. Clinical and laboratory reports were now in favor of spontaneous TLS [Table 1].
His lymph node histology reveals atypical lymphoid proliferation with completely effaced lymph node architecture. There is diffuse proliferation of intermediate-sized lymphoid cells in sheets. The cells have irregular nuclei and coarse chromatin and scanty cytoplasm. Mitoses are noted [Figure 3] and [Figure 4]. Amidist lymphoid proliferation, many eosinophils and few tingible body macrophages seen [Figure 3] and [Figure 4].
|Figure 3: Effaced lymph node architecture by atypical lymphoid proliferation|
On Immunohistochemistry (IHC), atypical cells diffusely express Leucocyte common antigen(LCA) and CD3 [Figure 5]. CD30 is focally positive in scattered cells. CD20 and PAX5 highlight small aggregates and scattered B cells. CD10 and TdT are negative [Figure 6]. MIB1-labeling index was around 75%. Based on histology and IHC study and recent investigations, the patient was finally diagnosed as PTCL-not otherwise specified (NOS) with hypereosinophilia and spontaneous TLS [Figure 5] and [Figure 6].
|Figure 5: Positive marker immunohistochemistry marker CD3 and leukocyte common antigen diffusely expressed
|Figure 6: Negative marker CD20 and PAX5 highlight small aggregates and scattered B-cells. CD10 and TdT are negative|
Appropriate chemotherapy for PTCL-NOS and injection NaHCO3 initiated for TLS. Further, the patient developed respiratory distress and hypotension, was started on vasopressor support, was intubated, and was started on mechanical ventilatory support. In spite of the aggressive management, patient deteriorated further and was died after 3 days.
PTCL is an uncommon variant of cutaneous TCLs and accounts for 10% of all cases of NHLs. It occurs in all age groups, although peak occurrence is in the sixth and seventh decades. PTCL-NOS is the most common PTCL subtype, making up about one-quarter of all PTCLs. It is also the most common of all the TCLs. The term PTCL can be confusing as it can refer to the entire spectrum of mature TCLs, but it can also refer to the specific PTCL-NOS subtype. Although most patients with PTCL-NOS are diagnosed with their disease confined to the lymph nodes, sites outside the lymph nodes, such as the liver, bone marrow, gastrointestinal tract, and skin, may also be involved.
Primary cutaneous PTCL-NOS are clinically heterogeneous, varying from localized to generalized plaques or nodules commonly associated with constitutional symptoms (B symptoms). Mild anemia, thrombocytopenia, elevated LDH, hypereosinophilia, and pruritus are common associations. Hypereosinophilia is also one of the paraneoplastic markers of lymphoma, and it is seen in up to 29% of the patients with PTCL.
Paraneoplastic eosinophilia represents a subset of secondary eosinophilia that appears due to tumor production of the eosinophil growth factors such as interleukin (IL)-3, IL-5, and granulocyte-macrophage colony stimulating factor. The most commonly associated malignancies are lymphomas and leukemias, but paraneoplastic eosinophilia may also be seen with lung, gastrointestinal, and gynecologic tumors. Clonal eosinophilia (chronic eosinophilic leukemia) is associated with gene rearrangements involving FIP1 L1, PDGFR α and β, and FGFR1. Other causes of secondary eosinophilia include allergic reactions, parasitic infections, and collagen vascular diseases. The end-organ damage occasionally seen with clonal eosinophilia, such as an infiltrative cardiomyopathy, has not been seen with paraneoplastic eosinophilia.
In this present case, patient had marked eosinophilia mimicking myeloproliferative neoplasm and chronic eosinophilic leukemia, but significant lymphadenopathy and high LDH levels make suspicion of lymphoma. Echocardiography was normal which favors paraneoplastic syndrome.
In PTCL-NOS, lymph node histology shows paracortical or diffuse infiltrate with effacement of normal architecture; Medium to large cells having irregular, pleomorphic, hyperchromatic, Vesicular nuclei, prominent nucleoli and many mitotic figures seen. An inflammatory background includes small lymphocytes, eosinophils, plasma cells, and clusters of epithelioid histiocytes.
The IHC panel often tests for anaplastic lymphoma kinase, CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD21, CD23, CD56, and CCD57. In general, T-cells often express CD2, CD3, CD4, CD5, CD7, or CD8, while B-cells do not. Flow cytometry may be done in addition to IHC panel.
Differential diagnosis includes angioimmunoblastic lymphoma, adult T-cell leukemia/lymphoma, anaplastic large-cell lymphoma, and T-cell-rich large B-cell lymphoma.
Treatment for PTCL aims to cure and includes the use of combination chemotherapy regimens – typically (cyclophosphamide, doxorubicin, vincristine, prednisone)-based chemotherapy or etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone – localized radiotherapy, stem cell transplants, and steroid therapy.
PTCLs are aggressive lymphomas with poor response to therapy, frequent relapses, and low 5-year survival. Morbidity and mortality increased with associated spontaneous TLS.
Acute spontaneous TLS has been usually described in association with hematologic malignancies such as leukemia and lymphoma. Rare reports of acute spontaneous TLS in solid tumor malignancies involved gastrointestinal adenocarcinoma, germ cell tumors, gastric carcinoma, inflammatory breast carcinoma, colon carcinoma, malignant pheochromocytoma, hepatocellular carcinoma, prostate cancer, and adenocarcinoma of the lung.
The exact mechanism of spontaneous TLS is still uncertain. Release of intracellular metabolites due to rapid tumor necrosis was suggested to play a role in the development of spontaneous acute TLS. By the destruction of tumor cells, a large amount of uric acid, potassium, phosphate, and purine metabolites circulate in the blood, leading to hyperuricemia, hyperkalemia, and hyperphosphatemia. Acute renal failure occurs due to the precipitation of calcium phosphate and uric acid. TLS, as a result of acute renal failure and multiorgan failure, leads to high morbidity and mortality.
In our case, patient’s vitals and renal and electrolytes were normal at the initial visit (3 days before); then, the patient developed spontaneous TLS leading to dyselectrolytemia, hepatitis, and AKI.
Peripheral T-cell lymphomas (TCLs) is a rare entity with generally nonspecific clinical sign and rarely associated with paraneoplastic syndrome such as hypereosinophilia and tendency to develop spontaneous TLS. Therefore early detection of PTCL necessary not only for early treatment but to prevents morbidity and mortality.
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