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are at later stages or accelerated phase and associated with poor prognosis[2,3]. Yamato et al.[4] reported atypical idic(Ph) chromosome along with t(7;12)(q10;q10) in a case of ALL. The isodicentric chromosomes can be heterogeneous in copy number, which leads to amplification and duplication of the hybrid BCR‑ABL gene and such gene amplification and genomic heterogeneity is reported to be associated with drug resistance.The prognosis of CML patients with idic(Ph) is poorly understood. In the present case, response to standard chemotherapy was very poor and ‑ complete remission was never achieved. However, the mean survival or the prognosis of CML cases with idic(Ph) chromosomes were not different from those of typical CML cases with single Ph chromosome. Szych et al.[5] reported idic(Ph) chromosomes in two imatinib mesylate resistant patients. In the present case idic(Ph) chromosome is probably causing resistance to therapy as patient’s response to standard chemotherapy was poor and no complete remission was achieved after follow‑up of two years. However, early detection may be helpful to the strategic treatment of such patients.

Correspondence to: Dr. Babu Rao Vundinti, E‑mail: [email protected]

References 1. 2. 3. 4. 5.

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PMID: *****

Department of Cytogenetics, National Institute of Immunohaematology (ICMR), 13th Floor, New Multistoried Building, K. E. M Hospital Campus, Parel, Mumbai, Maharashtra, India

Sir, This is a case report and a review of epidermal growth factor receptor (EGFR) mutated small cell lung cancer (SCLC). In 2005, Araki, et al. published the first report of cases of EGFR mutated SCLC case.[1] Since then, five case reports,[1‑3] a total of 14 patients with EGFR mutated SCLC have been demonstrated, including our case which we report here. A 68‑year old woman without smoking history was referred to our department due to an abnormal shadow [Figure 1]. Transbronchial lung biopsy (TBLB) was performed and SCLC was pathologically confirmed [Figure 2]. In terms of immunostaining, synaptophysin, thyroid transcription factor‑1

Website: www.indianjcancer.com DOI: 10.4103/0019-509X.146749

Vundinti BR, Kerketta L, Korgaonkar S, Vaidya S, Ghosh K

Small‑cell lung cancer with epidermal growth factor receptor mutation: Case report and review of literature

Whang‑Peng J, Knutsen TA, Lee EC. Dicentric Ph’ Chromosome. J Natl Cancer Inst 1973;51:2009‑12. Kovacs G, Georgii A, Mainzer K. Three isodicentric Philadelphia chromosomes in acute phase of chronic myeloid leukemia: A case report. Cancer Genet Cytogenet 1986;20:29‑33. Pernice F, Squadrito G, Saitta A, Mazza G, Musolino C.Isodicentric Philadelphia chromosome in accelerated phase of chronic myeloid leukemia. Cancer Genet Cytogenet 1993;66:113‑6. Yamamoto K, Nagata K, Morita Y, Inagaki K, Hamaguchi H. Isodicentric Philadelphia chromosome in acute lymphoblastic leukemia with der(7;12) (q10;q10). Leuk Res 2007;31:713‑8. Szych CM, Liesveld JL, Iqbal MA, Li L, Siebert S, Asmus C, et al.Isodicentric Philadelphia chromosomes in imatinibmesylate (Gleevec)‑resistant patients. Cancer Genet Cytogenet 2007;174:132‑7.

(TTF‑1), chromogranin A and cluster of differentiation (CD) 56 were positive and cytokeratin (CK) 5/6 was negative. EGFR mutation was detected because serum‑carcinoembryonic antigen (CEA) was significantly high and exon 19 was confirmed. She was diagnosed as SCLC with EGFR mutation. While first‑line chemotherapy with combination of carboplatin and etoposide and second‑line chemotherapy with aumurubicin (AMR) were initially effective, she relapsed. With PS of 2, then, gefitinib was administered as third‑line chemotherapy resulting in progressive disease. She is now receiving topotecan as fourth‑line chemotherapy. Generally, there is a definite relationship between cigarette smoking and the development of SCLC. The proportion

a

b

c

d

b

a

c

Figure 1: Chest radiography shows a lobulated lesion in the right upper lung field (a) Chest CT shows a well‑defined nodule with a little trabeculation on the right upper lobe (b) with pretracheal lymph node swelling (c)

384

Figure  2: Microscopic findings of TBLB specimens reveal cancer cells showing high N/C ratio H and E, stain) (a) Immunohistochemical staining images of the tumor cells were positive for thyroid transcription factor‑1 (b) and cluster of differentiation 56 (c) Cytokeratin 5/6 was negative (d)

Indian Journal of Cancer | July–September 2014 | Volume 51 | Issue 3

Letters to Editor

Table 1: Characteristics of patients with EGFR mutated SCLC and the outcomes Case

Age

Sex

Smoking history

Histology

EGFR mutations

EGFR‑TKI administered

Outcomes

Gefitinib Erlotinib Gefitinib Gefitinib Gefitinib Gefitinib

PR PR PR PD PR PD

Gefitinib

PD

1 2 3 4 5 6

72 45 81 54 73 74

Female Female Male Female Female Female

Never Never Ex‑smoker Never Never Never

SCLC SCLC SCLC SCLC SCLC/Adeno SCLC

Exonl9 Exonl9 Exonl8 Exonl9 Exonl8 Exonl8

(De1E746 A750) (De1L747 P7531nsQ) (G719A) (De1E746 A750) (L858R) (G719C)

Ours

69

Female

Never

SCLC

Exon19 (De1E746 A750)

Adeno, adenocarcinoma. Never, never smoker; EGFR=Epidermal growth factor receptor; SCLC=Small cell lung cancer

of women with SCLC has increased from 28% in 1973 to 50% in 2002.[3] In contrast, 9 (64.3%) were females and 10 (71.4%) of the 14 patients with EGFR mutated SCLC in this study never smoked. The epidemiology of EGFR mutated SCLC might be different from conventional SCLC. It is well known that EGFR‑TKI achieves a high response rate for mutated adenocarcinoma. [4] Four of the seven patients (57.1%) with EGFR mutated SCLC who received EGFR‑TKI showed partial response as shown in Table 1. EGFR‑TKI might be as effective for patients with EGFR mutated SCLC as adenocarcinoma with EGFR mutations. In terms of the EGFR mutation type, both exon 19 and 21 are thought to be very sensitive for EGFR‑TKI.[4] Two of the four patients (50%) with exon 19 had PR, two of the four patients (50%) showed PD. Ando, et al. documented that poor PS could be related to antitumor response.[5] PS 2, which is relatively good and could be a predictive factor in our case as well. Another prognostic factor for EGFR‑TKI could be exited and more cases should be investigated. Tatematsu, et al. reported that five of the 122 SCLC patients during seven years were confirmed with EGFR mutations. Combined type of SCLC and adenocacinoma were found in three of the five patients. Two of the three were found in resected tumors and the remaining one was confirmed by transbronchial lung biopsy (TBLB).[2] Our case might have been a combined type as well since TBLB specimens are not large enough to fully examine the lesion pathologically. Conclusion EGFR mutations should be examined in female patients who never smoked and who are showing a high CEA.

Lymphoma of bone masquerading as osteomyelitis and causing compartment syndrome of the leg

Sir, Primary lymphoma of bone (PLB) is an uncommon bone tumor and accounts for less than 5% of all malignant bone tumors. [1] PLB has been reported in patients as young as two years and as old as 88 years (mean age, 42 years).[2] We report a rare case of PLB with sclerotic lesion which initially misdiagnosed and treated as chronic osteomyelitis later on led to compartment syndrome of the leg. Indian Journal of Cancer | July–September 2014 | Volume 51 | Issue 3

The standard treatment for EGFR mutated SCLC is still unknown. More cases should be estimated and examined. Asai N, Ohkuni Y, Matsuda M1, Kaneko N Departments of Pulmonology and 1Oncology, Kameda Medical Center, Chiba, Japan Correspondence to: Dr. Nobuhiro Asai, E‑mail: [email protected]

References 1. 2. 3.

4. 5.

Araki J, Okamoto I, Suto R, Ichikawa Y, Sasaki J. Efficacy of the tyrosine kinase inhibitor gefitinib in a patient with metastatic small cell lung cancer. Lung Cancer 2005;48:141‑4. Tatematsu A, Shimizu J, Murakami Y, Horio Y, Nakamura S, Hida T, et al. Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 2008;14:6092‑96. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small‑cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24:4539‑44. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin‑paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947‑57. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non‑small‑cell lung cancer patients treated with gefitinib. J Clin Oncol 2006;24:2549‑56. Access this article online Quick Response Code:

Website: www.indianjcancer.com DOI: 10.4103/0019-509X.146753 PMID: *****

A 35‑year‑old female presented to us with complains of pain in right upper leg and gradually increasing swelling of the calf for the last four months. Patient did not have any history of trauma. On examination, temperature of skin over tibia was raised. The movements of knee, ankle, and hip joint were normal. There was no lymphadenopathy. Blood pressure, Chest radiograph, and blood investigations were normal. Radiograph of right leg showed sclerotic lesion in the upper tibia [Figure 1]. A presumptive clinical diagnosis of osteomyelitis and osteosarcoma was kept. CT scan was done which diagnosed the lesion as osteomyelitis. To confirm the diagnosis, open biopsy was done. Biopsy was also reported as chronic osteomyelitis. Patient was 385

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Small-cell lung cancer with epidermal growth factor receptor mutation: Case report and review of literature.

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