BACKGROUND AND OBJECTIVES

Non-Hodgkin Lymphoma (NHL) ranks 11th in cancer incidence and mortality in the Philippines with the combination chemotherapy composed of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) being commonly used as treatment. However, the addition of Rituximab to CHOP (R-CHOP) has been shown to exhibit higher response rates and longer remissions, potentially improving quality of life. Currently, there is conflicting evidence on the cost-utility of CHOP versus R-CHOP. The study aimed to describe the patient- and country-specific factors, and treatment modalities used for NHL and systematically review cost-utility evidence of R-CHOP versus CHOP in adult NHL patients.

A systematic literature search of cost-utility studies on R-CHOP versus CHOP for NHL treatment was performed on eight databases: PubMed/MEDLINE, Scopus, Web of Science, EBSCOHost, Cochrane, York Research Database, Centre for Reviews and Dissemination Database, and HERDIN, where 607 studies were identified. Upon screening using an eligibility criteria, 10 studies were included and critically assessed using four appraisal tools: CHEERS, Drummond, Cooper, and ECOBIAS. These were performed independently by two authors with a third author assisting to help reach a consensus.

All studies from high-income countries (HICs) (n=8) and low-middle-income country (LMIC) (n=1) suggested that R-CHOP was more cost-effective for NHL treatment than CHOP in terms of utility outcomes. The study conducted in a low-income country (LIC) (n=1) suggested the opposite, favoring CHOP over R-CHOP. Methodological differences such as perspective, discount rate, willingness-to-pay (WTP), time horizon, and economic model were observed. Methodological limitations include completeness of data reported and credibility of sources used.

The results of this review shall be interpreted with caution as those favoring R-CHOP over CHOP for NHL treatment in terms of cost-utility were concentrated in HICs. More economic evaluations from LICs, LMICs, and upper-middle income countries (UMICs) are needed for a robust conclusion. Additionally, establishing a universally recognized guideline for economic evaluations is essential to guide researchers effectively.

Introduction: Arginine vasopressin (AVP) deficiency is an uncommon but important presentation of infiltrative hypothalamic– pituitary disorders. In adults, isolated AVP deficiency with pituitary stalk thickening is diagnostically challenging, especially in the absence of systemic disease. Langerhans cell histiocytosis (LCH) is a rare cause and may precede systemic involvement by several years. Case: We report a 42-year-old male who presented in 2017 with polyuria and polydipsia, with urine output of up to 10 L/ day. AVP deficiency was confirmed by the water deprivation test, and desmopressin was initiated. Initial pituitary magnetic resonance imaging (MRI) was normal, baseline anterior pituitary hormonal evaluation was unremarkable, and contrast-enhanced computed tomography (CECT) of the thorax and abdomen showed no abnormalities. Repeat pituitary MRI 1 year later demonstrated loss of the posterior pituitary bright spot with pituitary stalk thickening. In the absence of systemic involvement, a presumptive diagnosis of lymphocytic hypophysitis was made, and pituitary biopsy was deferred due to the high procedural risk. Serial pituitary MRIs over the following years showed persistent infundibular thickening and continued absence of the posterior pituitary bright spot, without interval progression or development of additional hormonal deficiencies. The patient remained clinically stable until June 2024, when new-onset left hip pain prompted MRI, revealing a heterogeneous mass involving the femoral neck and intertrochanteric region with a pathological fracture. Histopathological examination following wide resection confirmed LCH, with negative BRAF V600 mutation. Postoperative PET scan revealed a multisystem disease involving the skeleton, lymph nodes, spine, and gastrointestinal tract, with no bone marrow involvement. He subsequently completed six cycles of intravenous methotrexate and cytarabine. Conclusion Adult-onset AVP deficiency may be the earliest manifestation of occult multisystem Langerhans cell histiocytosis. This case highlights the importance of longterm follow-up and reconsideration of the initial diagnosis when new systemic features emerge.
Histiocytosis, Langerhans-Cell

Introduction: Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of langerin-positive histiocytes. Endocrine involvement most frequently manifests as central diabetes insipidus or secondary hypothyroidism, caused by infiltration of the hypothalamic-pituitary axis. Conversely, direct infiltration of the thyroid gland leading to primary hypothyroidism is an exceptionally rare clinical entity, particularly when presenting concurrently with central disease. Case: A 21-year-old female with known right otic and multisystem LCH presented with septic shock secondary to a right ear abscess accompanied by polyuria and polydipsia. Physical examination revealed a palpable goiter. Clinical and biochemical evaluation confirmed central diabetes insipidus with associated anterior hypopituitarism (low adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone). However, concurrent thyroid function tests demonstrated overt primary hypothyroidism, evidenced by an appropriately elevated thyroid-stimulating hormone (26.19 mIU/L) and low free T4 (5.47 pmol/L), rather than the anticipated secondary hypothyroidism. Neck ultrasound showed diffuse thyroid enlargement with heterogeneous echotexture. Crucially, anti-thyroid peroxidase and anti-thyroglobulin antibodies were both negative, rendering Hashimoto’s thyroiditis highly unlikely. Although the patient declined confirmatory fine-needle aspiration, the constellation of a palpable goiter, characteristic ultrasonographic findings, negative autoimmunity, and active multisystem disease strongly supported a diagnosis of direct histiocytic infiltration of the thyroid gland. She was initiated on appropriate glucocorticoid coverage and subsequent levothyroxine replacement, alongside systemic intravenous cytarabine. Conclusion This case highlights a rare, mixed endocrine profile in multisystem LCH, demonstrating that pituitary and direct end-organ infiltration can coexist. Hypothyroidism in LCH patients with established central diabetes insipidus should not be reflexively assumed to be central in origin. A comprehensive diagnostic workup, including autoantibody screening, ultrasound, and ideally histopathological confirmation, is essential to accurately identify primary endocrine failure and guide appropriate clinical management in these complex cases.
Histiocytosis, Langerhans-Cell ; Hypothyroidism ; Pituitary Gland

Occult Breast Carcinomas (OBCs) are rare. History and physical examination alone may lead to misdiagnosis hence inappropriate investigative and treatment modalities. Diagnosis is difficult without tissue biopsy and extensive immunohistochemical staining. Presented here is a 74-year-old Filipino male with a 2-month history of axillary mass with erythematous skin, initially assessed as hidradenitis suppurativa failing to resolve with antibiotics. An excision biopsy revealed adenocarcinoma within the lymph nodes. Immunohistochemical stains confirmed a breast primary. Radiologic imaging showed no breast lesions and no distant metastasis. Axillary node dissection done showed metastasis to 5 in 14 nodes harvested, classifying him as OBC Stage IIIA (cT0pN2M0). He completed whole breast radiotherapy and chemotherapy. No tumor recurrence was documented thereafter. Although misdiagnosis is common, OBC is a condition to consider in male patients presenting with axillary lymphadenopathy.

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

Primary female genital system lymphoma(PFGSL)is a rare subtype of extranodal lymphoma and patients commonly present in the department of gynecology.At present,there is a lack of uniform standards for the treatment of PFGSL.Although the classification of lymphoid neoplasmas was updated by the World Health Organization classification of haematolymphoid tumors in 2016,PFGSL was still not elaborated in sufficient detail.Most cases of PFGSL are non-Hodgkin lymphoma,involving the ovary and cervix.In some cases,involvement of uterine corpus,vagina,and vulva is reported.In this article,we report two cases of non-Hodgkin lymphoma in the female genital system,one from the uterus and the other from the ovary.By presenting the diagnosis and treatment of the two cases and reviewing the literature,we aim to provide a reference for clinicians in recognizing and treating rare cases.
Female ; Humans ; Genital Neoplasms, Female/diagnosis* ; Lymphoma, Non-Hodgkin/diagnosis* ; Ovarian Neoplasms

Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a⁺ and CD207⁺ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans ; Bone Diseases/therapy* ; Histiocytosis, Langerhans-Cell/therapy*

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by extreme immune activation, resulting in pathologic inflammation that may be life-threatening. Early recognition is crucial since survival largely depends on early initiation of treatment which utilizes a combination of chemotherapy, immunotherapy and in some cases even bone marrow transplantation. OBJECTIVES: This study aims to describe the clinical characteristics, treatment received and outcome of patients diagnosed with HLH at the Philippine Children’s Medical Center from 2004 to 2017. MATERIALS AND METHODS: A retrospective analysis of records of children 0-18 years of age diagnosed with HLH from January 2004 to December 2017 was done. RESULTS: A total of 39 patients were included in the study which gave an incidence of 1.22 per 3000 patients admitted under 18 years of age. There were 29 males (74.4%) and 10 females (25.6%) with a male to female ratio of 2.9:1 Mean age was 6.12 ± 3.89 years. The average time from initial presentation to diagnosis was 6 weeks and 2 days. The most commonly seen clinical and laboratory features observed in these patients were fever (100%), splenomegaly (71.8%), anemia (87.17%), thrombocytopenia (79.48%) and hypertriglyceridemia (69.23%). Only 5 patients were confirmed to be familial HLH with 3 having XLP gene mutation, and one each having syntaxin and perforin gene mutations. Majority of patients received a combination of treatment based on the HLH 2004 regimen while almost one third only received antibiotics. Only 23% of patients survived during the study period and all but one of these patients received drug combinations based on the HLH 2004 protocol. CONCLUSIONS AND RECOMMENDATIONS HLH is a rare but important condition that must be recognized early and treated appropriately to optimize survival. The mortality rate of 39 patients seen in this institution is high. There is a need to better utilize the diagnostic criteria of the disease and to employ a more uniform treatment strategy. Increasing awareness among health care personnel can also improve case finding, characterization and treatment.
Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Lymphohistiocytosis, Hemophagocytic ; Philippines

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

A 4-year-old boy was admitted to the hospital with a 3-day history of rash and intermittent abdominal pain, during which abnormal results from routine blood tests were discovered. Initially, he presented with acute jaundice hepatitis and pancytopenia. The patient's condition progressed rapidly, with recurrent fever, worsening jaundice of the skin and sclera, and progressively worsening hepatosplenomegaly. Liver function impairment and bone marrow failure continued to deteriorate, while cytokine levels continued to rise. After excluding infections, autoimmune diseases, tumors, genetic metabolic disorders, and toxicities, the patient was diagnosed with hepatitis-associated aplastic anemia (HAAA) complicated by hemophagocytic lymphohistiocytosis (HLH). Following treatment with corticosteroids, plasma exchange, intravenous immunoglobulin, and liver protection therapy, the patient's symptoms partially alleviated. Aplastic anemia complicated by HLH is relatively uncommon, and HAAA complicated by HLH is even rarer, often presenting insidiously and severely. This paper presents a case of HAAA complicated by HLH and summarizes previously reported cases in the literature, providing references for the early diagnosis and treatment of this condition.
Humans ; Lymphohistiocytosis, Hemophagocytic/therapy* ; Male ; Anemia, Aplastic/complications* ; Child, Preschool ; Hepatitis/complications*