Aditya Jandial

Uterine Mass and Menorrhagia: A Rare Presentation of Acute Myeloid Leukemia with Arduous Clinical Course

Address for Correspondence: Dr. Kundan Mishra, Department of Internal Medicine, Postgraduate Institute of Medical Training and Research, Chandigarh, India e-mail: mishrak20@gmail.com ORCID ID: orcid.org/0000-0002-6325-2972 Received: 21 July 2017 Accepted: 1 December 2017 • DOI: 10.4274/balkanmedj.2017.0941 Available at www.balkanmedicaljournal.org Cite this article as: Mishra K, Muralidaran C, Jandial A, Mittal BR, Varma S. Uterine Mass and Menorrhagia: A Rare Presentation of Acute Myeloid Leukemia with Arduous Clinical Course. Balkan Med J 2018;35:282-4 ©Copyright 2018 by Trakya University Faculty of Medicine / The Balkan Medical Journal published by Galenos Publishing House. 1Department of Internal Medicine, Postgraduate Institute of Medical Training and Research, Chandigarh, India 2Department of Pathology, Postgraduate Institute of Medical Training and Research, Chandigarh, India 3Department of Nuclear Medicine, Postgraduate Institute of Medical Training and Research, Chandigarh, India Kundan Mishra1, Chandrasekaran Muralidaran2, Aditya Jandial1, B.R. Mittal3, Subhash Varma1

Real world experience with “generic” pomalidomide in relapsed refractory multiple myeloma

With keen interest, we read the experience shared by Scott et al. regarding the efficacy of pomalidomide in an Australian cohort of 151 patients with relapsed/refractory multiple myeloma (RRMM) treated in ‘real-world’ settings between 2010 and 2015 [1]. The authors reported an overall response rate (ORR) of 32% with a median progression-free survival (PFS) of 3.4 months and overall survival (OS) of 7.5 months. However, we would like to add that high cost and unavailability of newer anti-myeloma drugs have conventionally conferred a poor prognosis upon RRMM patients in resource-constrained settings [2,3]. Generic preparations of original formulations are commonly used in developing countries because of their low cost [4]. We would like to complement the observations of Scott et al. by sharing our experience of generic pomalidomide in RRMM since May 2017 when it became available in India. RRMM patients generally have a poor outcome because of poor performance status, cumulative burden of complications from previous therapies, and advanced disease per se [5]. Prospective randomized trials and realworld studies from developed countries have clearly demonstrated the role of pomalidomide in relapsed/ refractory myeloma [6–9]. We concur with the authors’ view that introduction of a therapy into routine clinical practice may or may not reflect the results of prospective randomized trials. Population-based studies are indispensable especially when they describe the patients who otherwise might not find representation in clinical trials. However, there are additional attributes which are unique to the developing world. Majority of the patients can’t afford the original (imported) drug formulations. Hence, it is reasonable to explore the efficacy and tolerability of generic formulations as an alternative in such patients who would otherwise be candidates for palliative care. Generic pomalidomide has been available in India since May 2017 (Pomalid launched by Natco Pharma Ltd., India). Although the same company continues to be its sole manufacturer in India, other indigenous companies have also started marketing generic pomalidomide under different brand names [Pomalong (Cipla Inc., India), Pomyelo (Intas pharmaceuticals Ltd., India), Pomahope (Abbott India Ltd., India), Pomired (Dr. Reddy’s Laboratories Ltd., India)] [10]. We used generic pomalidomide for a total of 24 RRMM patients from May 2017 to May 2018 at our institute. The choice of generic brand was decided by the patients. The median age was 63.5 years (range 3876). Ten patients had age >65 years and GFR less than 60ml/min was found in 9 patients. The patients had received a median of 4 prior therapies (range 2–7) and the median time from diagnosis to initiation of pomalidomide was 4.2 years (range 1–11.6); and, 13/24 patients (54.1%) had ECOG performance status 2. Fourteen patients (58.3%) had ISS stage 3 disease and 8 were prior autologous HSCT recipients. Seventy-five percent of patients (18 out of 24) were refractory to bortezomib as well as lenalidomide. Low platelet count (<75 10/L) before starting pomalidomide was found in 4/24 patients (16.7%). Results of FISH analysis were available for only 4 patients (1 patient had 17p deletion and 3 patients had 13q deletion). Majority of the patients (17/ 24) received pomalidomide plus dexamethasone (doublet therapy) and remaining 7 patients received a third drug [carfilzomib [3], bortezomib [2], or melphalan [2]] additionally (triplet therapy) since the beginning. Majority of the patients (16/24) received pomalidomide starting dose of 4mg daily for 21/28 days. The patients received a median of 6 cycles (range <1– 12). Five patients (20.8%) died during the study period, and 3 patients were lost to follow up. Three died because of febrile neutropenia with pneumonia before they could complete first cycle; one patient had progressive disease; and one patient with underlying coronary artery disease, who had discontinued pomalidomide after 2 weeks due to grade 4 thrombocytopenia, developed sudden cardiac arrest after receiving the first dose of daratumumab [11]. Grade 3 cytopenias were the most common serious adverse events (Table 1). Five patients (20.8%) required pomalidomide dose reduction. The overall response rate [defined as partial response (PR) or better] was 50%.

Macroglossia and amyloidosis

Macroglossia, often seen by physicians in clinical practice presents with difficulty in eating and speaking. The clinical examination was unremarkable except for enlarged tongue and difficulty in articulation. A tongue biopsy confirmed the diagnosis of amyloidosis and further evaluation confirmed the diagnosis of multiple myeloma. The index case emphasizes the need for through work-up in a case of an enlarged tongue with no apparent cause.

Diabetes mellitus and air crescent sign

A 66-year-old gentleman, presented with history of fever and cough for 2 weeks. He was a known case of diabetes mellitus type 2 for five years. He was febrile, had tachypnea, trachycardia and 96% oxygen saturation at room air. Chest auscultation revealed crackles in bilateral infrascapular area. Chest x-ray was within normal limit. Diagnosis of communityacquired pneumonia was made, he was admitted, and started on levofloxacin along with insulin therapy. On day three of therapy his condition worsened. CT-chest images showed bilateral lung consolidation with air lucency in between. Serum galactomannan was 5.5ng/mL. Bronchoalveolar lavage grew septate acute branching hyphae, proven to be Aspergillus on polymerase chain reaction (PCR). He was started on injection liposomal amphotericin.

Multiple myeloma and pepperpot skull

A 66-year-old gentleman presented with backache for 5 months duration. The pain was generalized over the vertebral column, it was persistent, progressive, aggravated by physical exertion and often got him awake from sleep. He also gave a history of loss of appetite and easy fatigability. There was no history of trauma, fever or peripheral joint pain. On examination, he had pallor and tongue was dry but rest of the physical examination was unremarkable. His skeletal survey showed multiple radiolucent, lytic lesions in the pelvic bone, thoracolumbar vertebra and skull (Figure 1). Further Investigations showed, anemia (Hb 82 g/l), raised creatinine (2.7 mg/dl) and hypercalcemia (13.7 mg/ dl). Bone marrow biopsy, showed 70% clonal plasma cells, confirming the diagnosis of multiple myeloma. Serum and urine electrophoresis revealed monoclonal protein. The patient was managed with rigorous hydration, forced diuresis and, dexamethasone. Subsequently, he received bortezomib, thalidomide and dexamethasone (VTd). Two months later, on follow up, he was asymptomatic. Musculoskeletal pain has a prevalence of 65–85% in elderly, and 36–70% of them have back pain. The back pain in the elderly can be viscerogenic, psychogenic or spondylogenic. The common causes of spondylogenic pain include trauma, degenerative disc diseases, metabolic disorders, inflammation, infection and neoplasms. Malignancy constitutes 1–7% of all causes. X-ray of the spine is the conventional first-line investigation and treatment depends upon the underlying cause. Multiple myeloma (MM) presents at an average age of 70 years. It accounts for 1–2% of all malignancy. Lytic lesions of bone are the hallmark of MM and are seen in 80% of patients at presentation. Lytic lesions can also be seen in hyperparathyroidism and skeletal metastasis. The presence of extensive osteolytic lesions and hypercalcemia portends a poor prognosis in MM. Presence of more than 10% clonal plasma cells in bone marrow, and monoclonal proteins in serum and urine confirm the diagnosis. The treatment includes chemotherapy and stem cell transplant along with bisphosphonates for bone health.

Pulmonary Arteriovenous Malformations

A 34-year-old gentleman, presented with a recurrent headache, redness of the face, and shortness of breath for six months. He had congestive palpebral conjunctiva, reddish face and drumstick appearance of the fingers with loss of Lovibond angle. His SpO2 82 % at room air. Investigation showed hemoglobin 250 g/L, hematocrit 69%, and pO2 of 44.4 mm of Hg. Erythropoietin (EPO) level was normal. CT pulmonary angiography images showed multiple pulmonary arteriovenous malformations (PAVMs) in the bilateral lower lobe of the lung. The patient underwent phlebotomy to relief the symptoms of hyperviscosity. PAVMs is abnormal communication between the pulmonary artery and pulmonary vein without capillary bed leading to right to left shunt physiology. It can be congenital (80% cases) and acquired (20%). Clinically PAVMs presents as a classical triad of dyspnea, cyanosis, and clubbing.

Night blindness, Bitot’s spot and vitamin A deficiency

A 19-year-old male, presented with gritting sensation in both the eyes and decrease vision during the night for one month. Eyes examination revealed whitish, foamy lesions on the temporal side of the ocular conjunctiva. The patient was treated with oral vitamin A 200,000 IU on day 0, 1, and at two weeks. Vitamin A deficiency is rampant in developing countries like India. It is more prevalent in children, and most common cause is malnutrition. Clinical symptoms and signs range from mild eye discomfort, night blindness to total loss of vision, which is grouped under a single entity, called as xerophthalmia. Bitots spots are a specific manifestation of Vitamin A deficiency. If untreated, it heralds the complete loss of vision.

Necrotising Ulcerative Gingivitis: A Rare Manifestation of Pseudomonas Infection

Management of intra-oral infections in immunocompromised patients can be potentially challenging and deceiving [1]. Opportunistic pathogens including bacteria, viruses and fungi are the major cause of necrotising intra-oral infections in immunocompromised patients [2]. Overlapping clinical features produced by various infective agents acting alone or in combination may challenge clinical judgement at bedside. We present a case of acute myeloid leukemia (AML) who developed Pseudomonas aeruginosa related necrotising ulcerative gingivitis. A 19-year-old girl, known case of AML, post allogenic hematopoietic stem cell transplant (HSCT) with graft failure was planned for second allogenic-HSCT. She presented on Day ? 128 with fever and exquisite gingival pain in right maxillary pre-molar region of 1-day duration. She also complained difficulty in opening the mouth and pain on chewing food. Neither she had any such complaint in the past nor did she develop any such symptoms during high dose chemotherapy and HSCT. At presentation, she had fever (101.2 F), tachycardia (112 beats/min) and tachypnea (26 breaths/min); her blood pressure was normal (114/72 mmHg). On oral cavity examination, generalised gingival erythema and edema was present (Fig. 1a) which was most conspicuous in right lateral maxillary region. A necrotic gingival plaque measuring 10 mm 9 10 mm was present alongside the right upper premolar tooth (Fig. 1b). Investigations revealed Hemoglobin 94 g/L, total leucocyte count 0.3 9 10/L, absolute neutrophil count 0.1 9 10/L and platelet count 64 9 10/L. Peripheral smear was unremarkable for blasts/atypical cells. A panoramic dental radiograph was normal. Blood and urine cultures were sterile. On bacterial culture, swab from necrotic gingival plaque revealed growth of Pseudomonas aeruginosa on day 3 of admission. Fungal smear and culture were unremarkable. Inj. Cefoperazone ? sulbactam (2 g IV TDS) and Inj. Vancomycin (1 g IV BD) were empirically started with supportive measures (Fentanyl transdermal patch and morphine IV boluses for pain relief; 1% clotrimazole mouth paint and chlorhexidine mouth rinses). On day 3 of admission, in view of high grade fever and persistent pain, gram negative cover was escalated from Cefoperazone ? sulbactam to Inj. Cefepime (2 g IV TDS) and Inj. Amikacin (750 mg IV OD). Vancomycin was stopped after sterile blood culture report. She became afebrile by day 5 of admission. Gingival pain subsided completely by day 9. Gingival swab culture repeated on day 5 of admission was sterile. By day 17 of admission, necrotic gingival tissue got completely dislodged by underlying healthy granulation tissue (Fig. 1c, d). Cefepime and Amikacin were administered for a total of 3 weeks. Intra-oral infections in immunocompromised patients result in substantial morbidity and mortality. These infections frequently lead to substantial pain and impaired feeding which in turn compromise tolerance and compliance to treatment especially in patients with haematological malignancies. It is well recognised that soft tissue infections in neutropenic patients have frequent association with little or no pus formation and favourably respond to prompt antimicrobial therapy. Clinical & Pankaj Malhotra hematpgi@gmail.com

“Everything that Glows on PET is not Lymphoma”: An Unheralded Intruder in a Case of Diffuse Large B Cell Lymphoma

Dear editor, Patients of diffuse large B cell lymphoma (DLBCL) with low (0–1) international prognostic score (IPI) has an expected 5 years survival of 73% [1]. RCHOP remains the standard first line chemotherapy. Infections during and after chemotherapy is often encountered and more so in developing countries. However, isolated muscle cysticercosis is an unusual infection and moreover, FDG avid mass like presentation of cysticercosis is extremely rare. The index case was a prototype of low risk (IPI-0) DLBCL who responded and became asymptomatic with chemotherapy. However, an unexpected and unusual presentation of cysticercosis kept everybody guessing. A 36-year-old gentleman presented with the complaints of low grade fever, weight loss and left cervical lymphadenopathy for 1-month duration. Left cervical lymph node excision biopsy was suggestive of diffuse large B cell lymphoma confirmed by immunohistochemistry. On further evaluation, he was found to have Ann Arbor stage IB disease on the basis of contrast enhanced CT (neck, chest, abdomen and pelvis) and bone marrow biopsy. As per our institutional protocol for early stage DLBCl, he was administered 4 cycles of R-CHOP chemotherapy followed by involved field radiotherapy. He came to follow up with end of treatment whole body PET-CT scan. He was asymptomatic, clinical examination was unremarkable. He had gained 4 kg weight in last 6 weeks and was subjectively feeling better. His hemoglobin was 120 g/L, WBC 6.9 9 109/L, and platelets 270 9 109/L with normal peripheral blood smear. However, the PET-CT revealed an isolated intensely FDG avid (SUV max 10.5) soft tissue mass with perilesional stranding in the right iliacus muscle having ill-defined fat planes with right psoas muscle (Fig. 1a, b) and also a central photopenia suggestive of necrosis. A PET-CT guided core biopsy was taken from the lesion and sent for histopathology. Multiple cores examined were composed of fibrous tissue with mixed inflammation comprising of lymphocytes, plasma cells and eosinophils (Fig. 2a). A separately lying fragment of tegment of parasite consistent with cysticercosis was also seen which was PAS positive (Fig. 2b). No evidence of any lymphomatous infiltrate was present. On further screening, cysticercosis was not seen anywhere else in the body (normal MRI brain). He was given a course of oral albendazole (400 mg OD 9 21 days). Two months later, the patient continues to be asymptomatic and repeat limited PET-CT showed complete disappearance of the lesion (Fig. 1c, d). Cysticercosis is not an uncommon endemic disease in the developing countries including India. It is caused by ingestion of eggs of pork tapeworm Taenia solium. The eggs are excreted in feces of infected human being (condition called teniasis) and contaminate the food materials, which on ingestion penetrates the intestine and reach organs like brain, eye, skeletal muscles or subcutaneous tissues [2]. The commonest organ involved is brain followed by eye, muscle or subcutaneous tissue but mostly a combination of two or more. However, it is rare to find an isolated muscle cysticercosis. As it can’t grow further, it remains dormant and undiagnosed forever and doesn’t & Pankaj Malhotra hematpgi@gmail.com

Multiple Granulocytic Sarcomas: A Rare Presentation of Acute Myeloid Leukemia

Dear editor, A 16-year-old boy, presented with gradually progressive, painless swelling over the back for 1-month duration followed by similar swellings over head and chest. He also noticed bulging of the right eyeball with double vision in last 1 week. Clinical examination revealed a thin built and cachexic young boy. He had multiple swellings over scalp (6 9 4 cm), chest wall (8 9 5 cm) and sacrum (5 9 2 cm, 3 9 2 cm) that were firm to hard, non-tender and adherent to the underlying structure (Fig. 1a, c, d). He also had proptosis of the right eye (Fig. 1b). Ocular movements and pupillary reflex were preserved. Rest of the clinical examination was unremarkable. His complete blood count showed, Hemoglobin 138 g/ L, WBC 3.6 9 10/L, and Platelets 260 9 10/L with a normal peripheral blood smear. A Whole-body PET CT showed intense FDG avid lesions corresponding to the clinically apparent sites along with a retro-orbital mass (Fig. 2). The histopathology report of the biopsied tissue from the sacral swelling was suggestive of non-Hodgkin lymphoma. Bone marrow aspiration-biopsy showed 26% MPO negative blast, which was positive for CD13, CD33, CD34, CD38, CD117 and HLA DR and Cytogenetic studies revealed t (8:21) (AML/ETO or RUNX1/ RUNX1T1). Diagnosis of Acute myeloid leukemia with recurrent cytogenetic abnormality t (8:21) (AML/ETO or RUNX1/RUNX1T1) was made. Because of the deplorable general condition, patient and the family agreed for hypomethylating agents as a bridge to the standard induction therapy. The patient succumbed to the illness after the first cycle of Decitabine due to sepsis and multi-organ dysfunction. Granulocytic sarcoma (GS), also known as myeloid sarcoma or chloromas have been described since 1811 [1]. Along with leukemia cutis, it is a well-defined extramedullary manifestation of acute myeloid leukemia. It constitutes a collection of immature cells of granulocytic origin and it is seen in 2.5–9.1% of AML cases [2]. Granulocytic sarcoma can precede, concur or follow the AML. It can present as a solitary lesion or multifocal lesion [3]. It can be virtually located in any part of the body and when present confer a poor clinical outcome [4]. Common differential diagnosis includes non-Hodgkin’s lymphoma, dendritic cell neoplasm, Ewing sarcoma, and melanoma [5]. Diagnosis depends on morphology, immunohistochemistry and flow cytometry. PET-CT is useful in detecting anatomically hidden GS, planning radiotherapy and assessing the response to therapy [4, 6]. The outcome of chemotherapy alone in patients presenting with granulocytic sarcoma is often disappointing. The standard treatment constitutes induction chemotherapy (7 ? 3) followed by hematopoietic stem cell transplantation [2]. A favorable risk is attributed to patients with t (8:21), and a good prognosis is expected from chemotherapy alone, but the outcome is significantly poor in the presence of GS even in the presence of t (8;14) and thus necessitates HSCT in complete remission after induction chemotherapy [4, 7]. The index case represents clinically apparent multiple granulocytic sarcoma as presenting feature of AML, which is extremely rare and may confuse the clinician with other solid malignancy. In the absence of clinical suspicion, even & Pankaj Malhotra hematpgi@gmail.com