Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:4110
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size

 Table of Contents    
Year : 2011  |  Volume : 28  |  Issue : 4  |  Page : 230-233
ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma

1 Department of Pathology, NYU Langone Medical Center, New York City, USA
2 Department of Surgery, NYU Langone Medical Center, New York City, USA

Click here for correspondence address and email

Date of Web Publication20-Oct-2011


Anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) has a vast morphologic spectrum and may mimic many other types of malignancies both cytologically and histologically. There are only a few published case reports/series describing the cytomorphologic features of ALCL on fine-needle aspiration (FNA) biopsy specimens. We describe a case of ALK-negative ALCL mimicking a high-grade soft tissue sarcoma of the thigh in a 62-year-old man. The characteristic morphologic findings on FNA and core biopsy along with the immunophenotypic profile are described and reviewed. The diagnosis of ALCL on FNA biopsy may be difficult, but can be done successfully with the use of ancillary tests. Therefore, it must be considered in the differential diagnosis of lesions with pleomorphism, anaplasia, and wreath-like or horseshoe-shaped nuclei to ensure that adequate material is obtained for ancillary studies.

Keywords: ALK-negative; anaplastic large cell lymphoma; cytology; fine-needle aspiration

How to cite this article:
Hudacko R, Rapkiewicz A, Berman RS, Simsir A. ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma. J Cytol 2011;28:230-3

How to cite this URL:
Hudacko R, Rapkiewicz A, Berman RS, Simsir A. ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma. J Cytol [serial online] 2011 [cited 2022 May 20];28:230-3. Available from:

   Introduction Top

Anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) is defined by the World Health Organization (WHO) as a CD30-positive T-cell lymphoma that is morphologically indistinct from ALK-positive ALCL. [1] As opposed to ALK-positive ALCL which typically occurs in children and young adults, the ALK-negative neoplasm occurs more commonly in adults with a median age of 58 years and has a worse prognosis. [2] It can involve lymph nodes and extranodal sites including skin, soft tissue, and the gastrointestinal tract. [2] The tumor is composed of large pleomorphic cells, some with prominent nucleoli and multinucleation, and shows a variable number of "hallmark" cells with horseshoe-shaped or kidney-shaped nuclei. [1] Morphologically, ALCL may mimic other types of lymphoma and may grow in a cohesive pattern mimicking nonhematologic malignancies such as sarcomas, carcinomas, germ cell tumors, and melanoma. Because the morphologic spectrum is so vast, the diagnosis of ALCL on fine-needle aspiration (FNA) cytology may pose a challenge to pathologists. We describe a case of ALCL mimicking a high-grade sarcoma on FNA cytology.

   Case Report Top

The patient is a 62-year-old man with a history of type-2 diabetes mellitus, hypertension, chronic inflammatory demyelinating polyneuritis, and Cushing's disease secondary to incomplete resection of a pituitary adenoma. He presented with deep vein thrombosis of the left leg with a subsequent episode 1 month later. At that time, a soft tissue mass was noted in the left thigh.

On physical examination, there was an approximately 6 cm mobile, irregular, firm mass located in the medial left thigh. Inguinal adenopathy and organomegaly were absent. Magnetic resonance imaging showed a lobular 6.3 × 5.4 × 3.4 cm mass in the medial subcutaneous fat of the proximal/mid left thigh. The mass was slightly hyperintense to muscle and demonstrated homogenous enhancement with a small area of hypoenhancement, suggestive of necrosis. It displaced the underlying musculature posterolaterally and appeared to extend to the skin. The differential diagnosis included synovial sarcoma, malignant fibrous histiocytoma (MFH), dermatofibrosarcoma protuberans, and nerve sheath tumor with malignant degeneration.

An ultrasound-guided FNA biopsy of the mass was performed using a 22-gauge needle. Four smears were fixed in 95% ethanol and stained using the Papanicolaou method, and four smears were air-dried and stained with modified Giemsa (Diff-Quik) (Differential Stain Kit, Newcomersupply, Middleton, WI). A compact cell block was prepared. A concurrent 18-gauge core needle biopsy (CNB) was also performed. Additional material was submitted for flow cytometry (FC) using standard techniques.

The FNA smears showed numerous discohesive, atypical round to polygonal to spindled cells with pleomorphic nuclei [Figure 1]. Scattered cells had abundant cytoplasm with multinucleation and prominent nucleoli best visualized on Papanicolaou stains. There were a few cells with nuclei with a wreath-like appearance [Figure 2]. Scattered mitotic figures were present. Inflammatory cells and lymphoglandular bodies were not identified. A high-grade sarcoma with a differential diagnosis of rhabdomyosarcoma and MFH was favored. Other diagnoses entertained were metastatic poorly differentiated carcinoma, melanoma, and high-grade non-Hodgkin lymphoma including anaplastic lymphoma.
Figure 1: Smear shows discohesive cells with pleomorphic nuclei and varying amounts of cytoplasm. Mitotic figures are noted by arrows (Diff-Quick stain, ×400)

Click here to view
Figure 2: Smear shows a cell with a wreath-like nucleus in the center. Prominent nucleoli are noted (Papanicolaou stain, ×400)

Click here to view

The concurrent CNB [Figure 3] showed dense connective tissue with a nodular and diffuse infiltrate composed of large cells with amphophilic cytoplasm and single, bi-, and multinucleation. Several horseshoe-shaped nuclei were noted. There were numerous mitotic figures. This was similar to the material obtained on the cell block preparation.
Figure 3: Section of the core needle biopsy shows cells with abundant amphophilic cytoplasm and pleomorphic nuclei, some with horseshoe-shaped and wreath-like nuclei (center) (H and E, ×500)

Click here to view

Immunohistochemistry (IHC) showed that the neoplastic cells were focally positive for CD2 and strongly positive for CD30 [Figure 4] with weak positivity for granzyme-B. The cells were negative for CD3, CD15, CD20, EMA, and ALK-1. FC detected a large population of atypical T-cells that were positive for CD2 and negative for CD3, CD4, CD8, CD38, CD138, and B-cell, monocytic, and myeloid markers. The final diagnosis was ALK-negative T-cell ALCL.
Figure 4: Immunohistochemical staining for CD30 shows strong cytoplasmic staining in the neoplastic cells (IHC, ×400)

Click here to view

   Discussion Top

There are only a few case reports/series describing the cytomorphologic features of ALCL on FNA biopsy. [3],[4],[5],[6] The largest series reported by Rapkiewicz et al. [3] reviewed 37 patients with ALCL of which only 13 cases were diagnosed initially as ALCL on FNA cytology specimens. The remainder of the diagnoses included non-Hodgkin lymphoma, Hodgkin lymphoma, nondiagnostic, atypical lymphocytes, and malignant neoplasm with a broad differential diagnosis of lymphoma, anaplastic carcinoma, and sarcoma. There was a variable degree of cellular pleomorphism and number of anaplastic cells on the FNA smears. The characteristic hallmark cells were found in only 11 of 20 reviewed aspiration specimens, of which eight cases had wreath-like multinucleated giant cells. Lymphoglandular bodies were not present in non-lymph node specimens. The study concluded that although difficult, ALCL can be accurately diagnosed on FNA specimens when aided by ancillary studies such as IHC. [3]

Our case showed similar cytomorphologic findings as some of the previously reported cases. A definitive diagnosis was established with FC and IHC. In general, FC and IHC can both be easily performed on aspirated material or concurrent CNB, depending on the preference of the individual laboratory. In our laboratory, CNB is the preferred method for the first time diagnosis of suspected lymphoid lesions based on immediate on-site evaluation of the aspirated material. Therefore, although the cell block was adequate, IHC was done on the concurrent CNB in this case.

In summary, diagnosing ALCL on FNA cytology is difficult given the spectrum of cytomorphologic findings but may be successfully done with the aid of ancillary tests, such as IHC and FC. The cytomorphologic features and immunocytochemical profiles of the most common entities in the differential diagnosis of ALCL on FNA cytology are listed in [Table 1]. It is important for cytopathologists to consider ALCL in the differential diagnosis of lesions characterized predominantly by discohesive, pleomorphic cells especially when anaplasia and/or horseshoe-shaped or wreath-like nuclei are present, and it is therefore essential to obtain adequate material for ancillary testing at the time of the procedure. This can be either in the form of additional passes for FC and cell block for FNA samples or concurrent CNB.[8]
Table 1: Cytomorphologic and immunocytochemical features of the differential diagnoses of anaplastic large cell lymphoma

Click here to view

   References Top

1.Mason DY, Harris NL, Delsos G, Stein H, Campo E, Kinney MC, et al. Anaplastic large cell lymphoma, ALK-negative. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 th ed, Lyon: International Agency for Research on Cancer; 2008. p. 317-9.  Back to cited text no. 1
2.Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood 2008;111:5496-504.  Back to cited text no. 2
3.Rapkiewicz A, Wen H, Sen F, Das K. Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology. Cancer 2007;111:499-507.  Back to cited text no. 3
4.Ng WK, Ip P, Choy C, Collins RJ. Cytologic and immunocytochemical findings of anaplastic large cell lymphoma: analysis of ten fine-needle aspiration specimens over a 9-year period. Cancer 2003;99:33-43.  Back to cited text no. 4
5.Rekhi B, Sridhar E, Viswanathan S, Shet TM, Jambhekar NA. ALK+anaplastic large cell lymphoma with cohesive, perivascular arrangements on cytology, mimicking a soft tissue sarcoma: a report of 2 cases. Acta Cytol 2010;54:75-8.  Back to cited text no. 5
6.Liu K, Dodd LG, Osborne BM, Martinez S, Olatdioye BA, Madden JF. Diagnosis of anaplastic large-cell lymphoma, including multifocal osseous Ki-1 lymphoma, by fine-needle aspiration biopsy. Diagn Cytopathol 1999;21:174-9.  Back to cited text no. 6
7.Caraway NP, Katz RL. Lymph nodes. In: Koss LG, Melamed MR (editors.) Koss' Diagnostic cytology and its histopathologic bases. 5 th ed, Vol II, Philadelphia: Lippincott Williams and Wilkins; 2006. p. 1215-6.  Back to cited text no. 7
8.Czerniak B, Tuziak T. Soft tissue lesions. In: Koss LG, Melamed MR (editors.) Koss' Diagnostic cytology and its histopathologic bases. 5 th ed, Vol II, Philadelphia: Lippincott Williams and Wilkins; 2006. p. 1309-21.  Back to cited text no. 8

Correspondence Address:
Rachel Hudacko
NYU Langone Medical Center, 530 First Avenue, Skirball West Tower, Suite 7-N, New York City, NY 10016
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.86362

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]

This article has been cited by
1 Anaplastic Lymphoma Kinase Positive Large B-cell Lymphoma Mimicking Metastatic Carcinoma of the Cervical Lymph Node from an Unknown Primary Lesion
Sang Woo Kim, Kyuho Lee, Bo Hae Kim, Eo Jin Kim
Korean Journal of Otorhinolaryngology-Head and Neck Surgery. 2021; 64(10): 760
[Pubmed] | [DOI]
2 A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology: The Sydney System
Mousa A. Al-Abbadi, Helena Barroca, Beata Bode-Lesniewska, Maria Calaminici, Nancy P. Caraway, David F. Chhieng, Immacolata Cozzolino, Mats Ehinger, Andrew S. Field, William R. Geddie, Ruth L. Katz, Oscar Lin, L. Jeffrey Medeiros, Sara E. Monaco, Arvind Rajwanshi, Fernando C. Schmitt, Philippe Vielh, Pio Zeppa
Acta Cytologica. 2020; 64(4): 306
[Pubmed] | [DOI]
3 Anaplastic large cell lymphoma: Report of two cases with rare patterns (carcinomatous and sarcomatous) in fine needle aspiration cytology and histopathology
Dilip K. Das, Mrinmay K. Mallik, Abdullah E. Ali, Fatemah ASK Khadom, Bency John, Mamoun Al-Ayanti
Diagnostic Cytopathology. 2020; 48(11): 1115
[Pubmed] | [DOI]
4 A Supraclavicular ALK-Positive Anaplastic Large-Cell Lymphoma Initially Misdiagnosed and Yet Successfully Treated with Wide Excision and Adjuvant Chemotherapy: a Case Report
Hervé Monka Lekuya,Edris Wamala Kalanzi,Ronald Mbiine,Abraham Omoding,Andreas Rosenwald,Gottfried Lemperle,Gerhard Bringmann
SN Comprehensive Clinical Medicine. 2019; 1(9): 716
[Pubmed] | [DOI]
5 Primary Soft Tissue Lymphomas: Description of Seven Cases and Review of the Literature
Alessandro Del Gobbo,Stefano Fiori,Giulia Ercoli,Andrea Di Bernardo,Antonina Parafioriti,Sonia Fabris,Alessandra Iurlo,Antonino Neri,Silvano Bosari,Umberto Gianelli
Pathology & Oncology Research. 2017; 23(2): 281
[Pubmed] | [DOI]
6 Fine-needle aspiration cytology yield as a basis for morphological, molecular, and cytogenetic diagnosis in alk-positive anaplastic large cell lymphoma with atypical clinical presentation
Maja Bogdanic,Slobodanka Ostojic Kolonic,Gordana Kaic,Mirjana Mariana Kardum Paro,Ruzica Lasan Trcic,Ika Kardum-Skelin
Diagnostic Cytopathology. 2017; 45(1): 51
[Pubmed] | [DOI]
7 Anaplastic large cell lymphoma with primary involvement of the skeletal muscle: A case report
Oncology Letters. 2015; 9(6): 2815
[Pubmed] | [DOI]
8 Extranodal anaplastic large cell lymphoma mimicking sarcoma: A report of an interesting case
Sujata Jetley,ZeebaS Jairajpuri,Safia Rana,Shaan Khetrapal,MajidA Talikoti
International Journal of Applied and Basic Medical Research. 2014; 4(3): 50
[Pubmed] | [DOI]
9 Epithelioid Rhabdomyosarcoma
Angelica Zin,Roberta Bertorelle,Patrizia Dall’Igna,Carla Manzitti,Claudio Gambini,Gianni Bisogno,Angelo Rosolen,Rita Alaggio
The American Journal of Surgical Pathology. 2014; 38(2): 273
[Pubmed] | [DOI]
10 epithelioid rhabdomyosarcoma: a clinicopathologic and molecular study
zin, a. and bertorelle, r. and dallæigna, p. and manzitti, c. and gambini, c. and bisogno, g. and rosolen, a. and alaggio, r.
american journal of surgical pathology. 2014; 38(2): 273-278
11 epidemiology, pathology, types and diagnosis of soft tissue sarcoma: a research review
banerjee, r. and bandopadhyay, d. and abilash, v.g.
asian journal of pharmaceutical and clinical research. 2013; 6(suppl.3): 18-25
12 Non-Hodgkin Lymphomas Presenting as Soft Tissue Masses: A Single Center Experience and Meta-Analysis of the Published Series
Enrico Derenzini,Beatrice Casadei,Cinzia Pellegrini,Lisa Argnani,Stefano Pileri,Pier Luigi Zinzani
Clinical Lymphoma Myeloma and Leukemia. 2013; 13(3): 258
[Pubmed] | [DOI]
13 Technologies supporting analytical cytology: Clinical, research and drug discovery applications
Cecic, I.K., Li, G., MacAulay, C.
Journal of Biophotonics. 2012; 5(4): 313-326
14 Anaplastic large cell lymphoma: The evolution continues
Das, D.K.
Journal of Cytology. 2011; 28(4): 233-234


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded97    
    Comments [Add]    
    Cited by others 14    

Recommend this journal