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Year : 2021  |  Volume : 58  |  Issue : 4  |  Page : 592--597

ALK-positive anaplastic large T-cell lymphoma presenting primarily as a sinonasal mass with pseudoproptosis: A case report

Siddhi G Sinai Khandeparkar, Priya Bagale, Smita Pathade, Bageshri Gogate, Shivani Battin 
 Department of Pathology, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India

Correspondence Address:
Siddhi G Sinai Khandeparkar
Department of Pathology, Smt. Kashibai Navale Medical College and General Hospital, Pune, Maharashtra


We report a case of anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma (ALK+ALCL) presenting primarily as a sinonasal mass with pseudoproptosis in an 11-year-old boy. The diagnosis was based on histopathological and immunohistochemical (IHC) evaluation, which is indispensable for determining tumor type. On the basis of clinicoradiological findings, provisional differential diagnoses of angiofibroma and rhabdomyosarcoma were made. Upon histopathological examination of the biopsy sent, the diagnosis of lymphoma in the sinonasal region was considered. Upon IHC, the tumor cells showed immunoreactivity for vimentin, CD45, CD30, and ALK. The tumor cells showed focal immunoreactivity for CD3 and CD68. Ki-67 labeling index was 70%. They were nonimmunoreactive for PAN cytokeratin, epithelial membrane antigen, cluster of differentiation (CD) 20, CD15, CD56, S100, smooth muscle actin, and myogenin. The diagnosis of ALK+ALCL was rendered. The studied IHC markers confirmed the histopathological diagnosis and helped in further subtyping. To the best of our knowledge, this is the first case of ALCL presenting primarily as a sinonasal mass with pseudoproptosis.

How to cite this article:
Sinai Khandeparkar SG, Bagale P, Pathade S, Gogate B, Battin S. ALK-positive anaplastic large T-cell lymphoma presenting primarily as a sinonasal mass with pseudoproptosis: A case report.Indian J Cancer 2021;58:592-597

How to cite this URL:
Sinai Khandeparkar SG, Bagale P, Pathade S, Gogate B, Battin S. ALK-positive anaplastic large T-cell lymphoma presenting primarily as a sinonasal mass with pseudoproptosis: A case report. Indian J Cancer [serial online] 2021 [cited 2022 Sep 28 ];58:592-597
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Anaplastic large-cell lymphoma (ALCL) comprises less than 5% of all cases of non-Hodgkin's lymphoma (NHL). Its primary location in the nasal cavity is infrequent.[1] Data are available as isolated case reports and small case series.[2],[3] High-grade B-cell lymphomas tend to present with soft tissue or bony destruction, particularly, of the orbit with associated proptosis. T-cell lymphomas of nasal cavity present with nasal septal perforation and/or destruction.[4] We encountered a case of anaplastic lymphoma kinase (ALK) positive (+) ALCL presenting as a sinonasal mass with pseudoproptosis in an 11-year-old male, which was biopsied. The studied immunohistochemical (IHC) markers confirmed the histopathological diagnosis, which prompted us to report this case. To the best of our knowledge, this is the first case of ALCL presenting primarily as a sinonasal mass with pseudoproptosis.

 Case Report

Clinical history

An 11-year-old boy was brought to ear–nose–throat outpatient department. He presented with swelling of the left eye for 2 weeks following blunt trauma. Patient also had cough and runny nose, at times blood stained on sneezing. He was all right 6 months back when he developed a left-sided headache, which was acute in onset, gradual in progression, and not relieved on taking medication. Local examination showed a mass in the left nasal cavity that bled on touch. There was no clinically significant peripheral lymphadenopathy. Computed tomography (CT) of the paranasal region showed a mass in the left maxillary sinus with the retro-orbital extension [Figure 1]a,[Figure 1]b,[Figure 1]c,[Figure 1]d. Magnetic resonance imaging (MRI) showed T2 iso to hyperintense lesion with a central necrotic area involving the left maxillary and ethmoidal sinuses and nasal cavity extending in the intraconal compartment of left orbit measuring 3.4 × 2.3 × 2.1 cm closely abutting the cribriform plate, into the nasopharynx, left pterygopalatine, and infratemporal fossa [Figure 2]. Differential diagnoses (d/d) of angiofibroma and rhabdomyosarcoma were offered.{Figure 1}{Figure 2}

The biopsy was sent from representative sites. On gross examination, multiple brownish-white, friable soft tissue bits were received aggregating to 3 cc. Microscopically, the bits were composed of areas of infarction necrosis with a large round to oval tumor cells having a pleomorphic nucleus, prominent nucleoli, and scant-to-moderate amount of clear cytoplasm admixed with the lymphoid population. A few of the tumor cells were large having abundant clear cytoplasm, horseshoe-shaped nuclei with the perinuclear eosinophilic region. There were atypical mitotic figures. A few nasal glands lined by columnar epithelium were seen. The diagnosis of lymphoma was considered [Figure 3]a.{Figure 3}

IHC was performed. The tumor cells showed immunoreactivity for vimentin, cluster of differentiation (CD) 45, CD30, and ALK. The tumor cells showed focal immunoreactivity for CD3 and CD68. Ki-67 labeling index was 70%. They were nonimmunoreactive for PAN cytokeratin (PAN CK), epithelial membrane antigen (EMA), CD20, CD15, CD56, S100, smooth muscle actin (SMA), and myogenin [Figure 3]b,[Figure 3]c,[Figure 3]d,[Figure 3]e,[Figure 3]f,[Figure 3]g,[Figure 3]h. The diagnosis of ALK+ALCL (lymphohistiocytic pattern) was rendered. Fluorescence in situ hybridization (FISH) analysis showed ALK1 gene rearrangement [Figure 3]i.

Positron emission tomography (PET) CT scan showed fluorodeoxyglucose (FDG) avid left nasal cavity mass involving the ethmoid maxillary sinuses extending into the premaxillary region and left orbit with a few FDG avid left upper cervical lymph nodes, such as posterior triangle neck node measuring 1.6 × 0.8 cm and left level IB node measuring 1 cm in diameter. The underlying bone showed no erosions. No FDG avid lesions were seen in the lung, liver, spleen, adrenals, or skeleton. There was no thoracic, abdominal, and pelvic lymphadenopathy on the PET-CT scan [Figure 1]e,[Figure 1]f,[Figure 1]g,[Figure 1]h. The complete hemogram was unremarkable. Bilateral bone marrow aspiration showed the presence of a few large atypical cells. Bilateral trephine biopsy showed the presence of large clusters, sheets, and scattered large atypical cells infiltrating the marrow spaces at places showing hallmark cells. Cerebrospinal fluid cytology was unremarkable. Biochemical investigations, such as renal and liver function tests, serum calcium, and serum phosphorous were within normal limits. Erythrocyte sedimentation rate was 10 mm/h and serum lactate dehydrogenase (LDH) was 170 U/L. Other systemic examination findings were noncontributory. Thus, the patient was classified as stage IV (Ann Arbor classification), with an international prognostic index (IPI) estimated at one (low risk). The child was referred to an oncology center for further management.

The patient was started on chemotherapy for high-risk patients according to the current protocol for ALCL (International Protocol for the Treatment of Childhood Anaplastic Lymphoma—ALCL99). He was administered: (1) an initial course of intravenous dexamethasone, cyclophosphamide, and intrathecal infusion of a combination of methotrexate, cytarabine, and hydrocortisone, (2) a cycle of A1 regime of dexamethasone, low dose of methotrexate, cytarabine, etoposide, and ifosfamide, and (3) later, alternating two cycles of BV/AV regimens every 3 weeks (BV: dexamethasone, cyclophosphamide, doxorubicin, a low dose of methotrexate, and vinblastine; AV: dexamethasone, a low dose of methotrexate, cytarabine, etoposide, ifosfamide, and vinblastine). Our patient did not receive the last BV cycle and maintenance chemotherapy (vinblastine/week for 1 year). The patient had grade 2 oral mucositis after each of the chemotherapy cycles. Prophylactic Granulocyte colony stimulating factor (GCSF) was not recommended as per the protocol. He had grade 4 neutropenia (absolute neutrophilic count [ANC] = 400/cu mm) on two occasions (5 days after the second cycle of chemotherapy and 10 days after the third cycle of chemotherapy) for which he received GCSF. The patient achieved remission (complete resolution of imaging [Figure 2]j and [Figure 2]l and bilateral bone marrow and trephine biopsy findings) of all initially involved areas after 1 month of chemotherapy.. Currently, he is disease-free since a period of 6 months.

Ethical clearance was obtained from the institute's ethical committee. Appropriate consent was obtained from the patient's parent.


ALCL was first described by Stein et al. in 1985. It manifests as primary ALK+ and ALK-negative (−) systemic and a cutaneous form. It accounts for 10–15% of pediatric and adolescent NHLs and 30–40% of total pediatric large-cell lymphomas.[2] ALK+ALCL involves both lymph nodes and extranodal sites. The commonly involved extranodal sites are the skin, bone, soft tissues, lungs, and liver.[3]

ALK+ALCL presenting primarily in the sinonasal region is extremely rare, and this causes its frequent misclassification and thus inappropriate management.[5] Accurate diagnosis is based on a high index of suspicion and immunohistopathological evaluation, which is indispensable for determining tumor type. The clinicopathological d/d at this site includes angiofibroma, nasopharyngeal carcinoma, olfactory neuroblastoma, and rhabdomyosarcoma, Hodgkin's lymphoma, extranodal NK/T-cell lymphoma (nasal type), diffuse large B-cell lymphoma, and Langerhans cell histiocytosis (LCH).[6],[7]

Histopathologically, the tumor is composed of a large number of cohesively arranged anaplastic large cells with abundant cytoplasm, wreath-like nuclei, perinuclear eosinophilic region (“hallmark/horseshoe/doughnut” cells) exhibiting brisk mitotic activity in a lymphoid background.[2] In this case, the hallmark cells resembled popcorn and lacunar variant of Reed–Sternberg (RS) cells. However, on IHC, the hallmark cells were positive for CD45, ALK, and CD30 and negative for CD15 and CD20 as against nodular sclerosis HL subtype, in which, a lacunar variant of RS cells are positive for CD15 and CD30 and negative for CD45 and ALK and lymphocyte predominance HL type, in which, the popcorn RS cells are positive for CD20 and CD45 and negative for CD30, CD15, and ALK.[8] The absence of PAN CK along with the age of the patient helped us rule out nasopharyngeal carcinoma.[9] The S100 negativity together with the absence of eosinophils and the presence of brisk mitotic activity in the tumor negated LCH.[10] The NK/T-cell lymphoma shows features like extensive coagulative necrosis and CD3 immunoexpression as seen in this case. However, absence of histopathological features such as angiocentric distribution of tumor cells and the presence of intact mucosal glands along with negative CD20 and CD56 and positive ALK immunoexpression helped us exclude the diagnosis in this case.[11] The absence of characteristic histopathological features, lack of SMA, and myogenin expression ruled out the clinical possibility of rhabdomyosarcoma and angiofibroma.

Most ALK+ cases are positive for EMA, which is an adverse prognostic feature. Prognosis in ALK+ALCL is good overall, except for the small cell variant or the subset that expresses CD56. The present case did not express EMA and CD56.[12]

The detection of ALK protein correlates nearly 100% with the presence of a chromosomal rearrangement involving ALK as seen in this case; thus, IHC has largely replaced molecular testing.[13] ALK+ALCL has a t(2;5)(p23;q35) signature translocation.[14] The nucleophosmin-ALK fusion protein is present in 80% of the cases.[15] ALK is a transmembrane receptor tyrosine kinase that participates in the signaling pathways of the central and peripheral nervous systems.[2] It is known that approximately 60% of systemic ALCL is ALK+ and have a significantly superior survival to ALK− cases.[14] Normal LDH, IPI score of ≤3, and CD56 negativity are mentioned as independent predictors of a better outcome.[14]

Multiagent chemotherapy used in ALK+ALCL cures approximately 65–90% of patients. A retrospective analysis of trials by NHL-Berlin-Frankfurt-Münster (NHL-BFM) working group revealed an 83% 9-year event-free survival (EFS) and overall survival (OS) of 81% for CD30-positive ALCL patients. NHL-BFM90 was the first trial to include a treatment arm specifically for ALCL that led to 5-year EFS of 100%, 73%, and 79% for arms K1, K2, and K3, respectively. It was recommended as the standard therapy for ALCL owing to its shorter duration and lower drug doses when compared with HM89 and HM91 protocols tested by the French Society for Paediatric Oncology (SFOP). Due to a high risk of short-term side effects associated with methotrexate, lower concentrations administered in shorter pulses were investigated in the NHL-BFM95 trial. The European Intergroup for Childhood NHL (EICNHL) launched the first international randomized trial for ALCL patients under the age of 22 years, regardless of ALK status, in 1999 (ALCL99 trial). The trial tested four different protocols to lower the amount of methotrexate required to rid the protocol of intrathecal injections and test whether vinblastine could be a valuable addition to the protocol. The trial achieved a 2-year EFS of 74.1% and a 2-year OS of 92.5%. On the basis of this trial, the investigators recommended using short-pulse, high-dose methotrexate without intrathecal injections for reduced toxicity and improved quality of life. Relapse following ALCL99 was comparable with previous trials averaging at 20–40%. However, these children still suffer long-term side effects of toxic chemotherapy.[15],[16]

Two small retrospective studies conducted by the SFOP showed that vinblastine could reduce the risk of treatment failure, even for patients who had relapsed on chemotherapy. Hence, as a part of the ALCL99 protocol, vinblastine was investigated in high-risk patients. Results showed a significant improvement over the first year of treatment in terms of EFS; however, overall, there was no significant difference between EFS and OS. Relapse was delayed rather than prevented.” Vinblastine was also investigated as frontline therapy in the Children's Oncology Group trial ANHL0131 (NCT00059839), in addition to the chemotherapy backbone (APO: doxorubicin, prednisone, vincristine, methotrexate, and 6-mercaptopurine). Like the European trial, it did not find any significant difference between 3-year OS or EFS as compared with standard chemotherapy; however, it did show that weekly vinblastine administration was more toxic than the “no vinblastine” arm. For both ANHL0131 and ALCL99-VBL, the vinblastine dose started at 6 mg/m2 but had to be reduced to 4 mg/m2 because of toxicity in most patients. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. Recently, the development of novel therapies targeting CD30 and ALK appears favorable. The advent of immune therapies, such as checkpoint inhibition, has provided another option for the treatment of ALCL. The number of potential new agents now presents a real challenge to the clinical community that must prioritize those thought to offer the most promise for the future.[15],[16] In adult patients with limited-stage (stage I/II) ALCL, combined modality treatment in the form of 3-6 cycles of CHOP/CHOEP (cyclophosphamide, doxorubicin, vincristine, and prednisone/cyclophosphamide, doxorubicin, etoposide, vincristine, and prednisone) regimen followed by consolidation radiotherapy is also an acceptable treatment option.[5]

Our experience with this case highlights the rarity of the lesion and the significance of high index of suspicion and detailed IHC analysis in a case of childhood sinonasal masses with proptosis for identifying this distinct histological subtype.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


We would like to thank Dr. Sanjana Nemade, Professor, Department of E.N.T, Smt. Kashibai Navale Medical College and Hospital, Pune who performed the biopsy; Pediatric Hematology and oncology unit, Pediatric department, Bharati Vidyapeeth hospital, Pune who carried out the further management of the patient; and Dr. Aditi Dastane for processing, reporting, and providing photographs of ALK gene rearrangement by FISH done in Deenanath Mangeshkar Hospital, Pune.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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