Introduction: Anaplastic large cell lymphoma (ALCL) is a rare mature T-cell non-Hodgkin’s lymphoma characterized by large and pleomorphic neoplastic CD30-positive T cells. ALCL includes different subtypes with different clinical and biological features: systemic ALCL, primary cutaneous ALCL, breast implant-associated ALCL (BIA-ALCL). Anaplastic lymphoma kinase (ALK) is overexpressed and rearranged in some systemic cases. Diagnosis of ALCL may be challenging on cytological samples, but the correct diagnosis is mandatory for the management of the patient. Methods: A retrospective series of 12 ALCLs diagnosed by cytology is reported. Cytological samples included lymph nodes and skin lesions fine needle aspiration cytology, peritoneal effusion, and periprosthetic fluid. Microscopic evaluation was performed on direct smears, cell-block sections, and cytocentrifugated slides. Immunocytochemistry was performed on cell-block sections, direct smears, and cytocentrifugated slides. Molecular evaluation by fluorescent in-situ hybridization (FISH) was performed on cell-block sections. Results: The series included 4 ALK+ ALCLs, 5 ALK− ALCLs, and 3 BIA-ALCLs. FNAC was performed on lymph nodes in 8 cases and on skin lesion in 1 case. In this last case, a peritoneal effusion was also evaluated. Breast periprosthetic fluids were evaluated in 3 cases. A large immunocytochemical panel was performed in each case, and FISH in 3 cases, demonstrating ALK rearrangement in a case of ALK+ ALCL. A final diagnosis was rendered in all cases. In the case of skin lesion, the differential diagnosis between systemic ALCL and primary cutaneous ALCL was possible. Conclusion: The cytological diagnosis of ALCL may be challenging, and the proper management of the collected sample is mandatory. The rapid on-site evaluation and the realization of a cell block are strongly recommended. Immunocytochemistry is mandatory for the diagnosis and a large antibodies panel is needed as differential diagnosis includes many different neoplasms. FISH may be useful to evaluate ALK rearrangements. When properly managed, cytology can lead to a reliable final diagnosis of ALCL.

Stein H, Foss HD, Dürkop H, Marafioti T, Delsol G, Pulford K, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681–95.
Pittaluga S, Wlodarska I, Pulford K, Campo E, Morris SW, Van den Berghe H, et al. The monoclonal antibody ALK1 identifies a distinct morphological subtype of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements. Am J Pathol. 1997;151(2):343–51.
Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe MJ, et al. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood. 1998;91(6):2076–84.
Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473–80.
Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768–85.
Massone C, El-Shabrawi-Caelen L, Kerl H, Cerroni L. The morphologic spectrum of primary cutaneous anaplastic large T-cell lymphoma: a histopathologic study on 66 biopsy specimens from 47 patients with report of rare variants. J Cutan Pathol. 2008;35(1):46–53.
Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE, et al. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol. 2014;32(2):114–20.
Derringer GA, Cotton JP, Melemed AS, Treadwell PA, Hood AF. Extranodal spread of anaplastic large cell (CD30+) lymphoma presenting as a cutaneous perivascular infiltrate. J Cutan Pathol. 1996;23(4):323–7.
Mandal S, Varma K, Jain S. Multiple cutaneous relapses in an adolescent in anaplastic large cell lymphoma diagnosed by FNAC. Cytopathology. 2008;19(2):127–9.
Al-Abbadi MA, Barroca H, Bode-Lesniewska B, Calaminici M, Caraway NP, Chhieng DF, et al. A proposal for the performance, classification, and reporting of lymph node fine-needle aspiration cytopathology: the sydney system. Acta Cytol. 2020;64(4):306–22.
Cozzolino I, Rocco M, Villani G, Picardi M. Lymph node fine-needle cytology of non-hodgkin lymphoma: diagnosis and classification by flow cytometry. Acta Cytol. 2016;60(4):302–14.
Ronchi A, Caputo A, Pagliuca F, Montella M, Marino FZ, Zeppa P, et al. Lymph node fine needle aspiration cytology (FNAC) in paediatric patients: why not? Diagnostic accuracy of FNAC in a series of heterogeneous paediatric lymphadenopathies. Pathol Res Pract. 2021;217:153294.
Zeppa P, Picardi M, Cozzolino I, Troncone G, Lucariello A, De Renzo A, et al. Fine-needle aspiration cytology in the follow-up of Hodgkin lymphoma. Diagn Cytopathol. 2008;36(7):467–72.
Barroca H, Bode-Lesniewska B, Cozzolino I, Zeppa P. Management of cytologic material, preanalytic procedures and biobanking in lymph node cytopathology. Cytopathology. 2019;30(1):17–30.
Al-Abbadi M, Barroca H, Bode-Lesniewska B, Calaminici M, Chhieng DC, Cozzolino I, et al. Letter to the Editor: fine-needle aspiration cytology and core-needle biopsy in the diagnosis of lymphadenopathies: words of endorsement. Eur J Haematol. 2021;107(2):295–6.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid TissuesRevised. 4th ed. In: WHO classification of tumours. Lyon: IARC Press; 2017. Vol. 2.
Das DK, Mallik MK, Ali AE, Khadom FA, John B, Al-Ayanti M. Anaplastic large cell lymphoma: report of two cases with rare patterns (carcinomatous and sarcomatous) in fine needle aspiration cytology and histopathology. Diagn Cytopathol. 2020;48(11):1115–20.
Ramteke P, Chitragar S, Singh A, Mallick S, Mathur SR, Jain D, et al. Anaplastic lymphoma kinase immunocytochemistry in fine needle aspiration diagnosis of anaplastic large-cell lymphoma. J Cytol. 2018;35(1):37–40.
Rapkiewicz A, Wen H, Sen F, Das K. Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology. Cancer. 2007;111(6):499–507.
Agnihotri MA, Kothari KS, Naik LP, Patil S. Anaplastic large cell lymphoma: a great mimic on cytology. J Cytol. 2017;34(3):165–7.
McCluggage WG, Anderson N, Herron B, Caughley L. Fine needle aspiration cytology, histology and immunohistochemistry of anaplastic large cell Ki-1-positive lymphoma. A report of three cases. Acta Cytol. 1996;40(4):779–85.
Falini B, Mason DY. Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry. Blood. 2002;99(2):409–26.
Rosario-Quiñones F, Strauchen JA, Salem F. Anaplastic large cell lymphoma masquerading as classical Hodgkin lymphoma on fine needle aspiration: a potential diagnostic pitfall. Diagn Cytopathol. 2015;43(11):916–9.
Cozzolino I, Vitagliano G, Caputo A, Montella M, Franco R, Ciancia G, et al. CD15, CD30, and PAX5 evaluation in Hodgkin’s lymphoma on fine-needle aspiration cytology samples. Diagn Cytopathol. 2020;48(3):211–6.
Bogdanic M, Ostojic Kolonic S, Kaic G, Kardum Paro MM, Lasan Trcic R, Kardum-Skelin I. 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. Diagn Cytopathol. 2017;45(1):51–4.
Ronchi A, Montella M, Zito Marino F, Argenziano G, Moscarella E, Brancaccio G, et al. Cytologic diagnosis of metastatic melanoma by FNA: a practical review. Cancer Cytopathol. 2022;130(1):18–29.
Ferreri AJM, Govi S, Pileri SA, Savage KJ. Anaplastic large cell lymphoma, ALK-positive. Crit Rev Oncol Hematol. 2012;83(2):293–302.
Jacobsen E. Anaplastic large-cell lymphoma, T-/null-cell type. Oncologist. 2006;11(7):831–40.
Clemens MW, Medeiros LJ, Butler CE, Hunt KK, Fanale MA, Horwitz S, et al. Complete Surgical Excision is essential for the management of patients with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol. 2016;34(2):160–8.
Laurent C, Delas A, Gaulard P, Haioun C, Moreau A, Xerri L, et al. Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes. Ann Oncol. 2016;27(2):306–14.
Ronchi A, Montella M, Argenzio V, Lucia A, De Renzo A, Alfano R, et al. Diagnosis of anaplastic large cell lymphoma on late peri-implant breast seroma: management of cytological sample by an integrated approach. Cytopathology. 2018;29(3):294–9.
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