Imprint cytology facilitating the diagnosis of primary cutaneous anaplastic large cell lymphoma of iliac fossa.

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a form of cutaneous T-cell lymphoma that is characterized by solitary nodules and plaques. In this report, the authors present an unusual case of a 59-year-old male with a solitary ulcerofungative mass in the left iliac fossa clinically masquerading as sqaumous cell carcinoma. The imprint smears of the lesion had characterstic morphological features which helped in the diagnosis. Subsequently, the imprint cytology correlated well with the histopathology and immunohistochemical studies highlighting its utility as simple, rapid, and easy test.

Introduction

Anaplastic large cell lymphoma (ALCL) is an uncommon non-Hodgkin lymphoma with both systemic and cutaneous forms.[1] Primary cutaneous anaplastic CD 30+ large cell lymphoma is a rare anaplastic large T-cell CD 30+ lymphoma originating in and confined to skin.[2] Atypical gross morphology may result in false clinical suggestion of squamous cell carcinoma.[3] There are case reports on primary cutaneous lymphoma on histopathology but only few case reports are available on cytopathology.[4] They can be easily misdiagnosed as carcinoma or melanoma by observers who are not familiar with this type of lymphoma.[5] The authors present an unusual case of an ulcerofungative mass in the left iliac fossa clinically masquerading as squamous cell carcinoma which was diagnosed as primary cutaneous anaplastic large cell lymphoma on imprint cytology. Subsequent biopsy findings and immunohistochemical studies correlated well with imprint cytology, highlighting its importance in the primary diagnosis.

Case Report

A 59-year-old man presented in skin department with large beefy red ulcerofungative mass in the left iliac fossa measuring 6×4×1 cm which was a small nodule 2 months back.

Computed tomography (CT) scan showed the presence of soft tissue mass with irregular outlines arising from the skin. There was no nodal or any other organ involvement in the body. With high clinical suspicion of squamous cell carcinoma, biopsy of the mass and imprint smears were taken.

The imprint smears were stained with Giemsa and showed isolated tumor cells. The tumor cells were predominantly round in shape having moderate to abundant cytoplasm with a well-defined cytoplasmic membrane and accentuated cell borders. At places, cytoplasmic blebbing was seen. The nuclei were central to eccentric showing variation in size and shape, had irregular nuclear membranes with fine chromatin and variably prominent nucleoli [Figure 1a]. The smears also showed characteristic hallmark cells with horseshoe shape/reniform nuclei [Figure 1b], plasmacytoid cells, occasional hand mirror cells with eccentric nucleus and elongated cytoplasm [Figure 1c] and occasional doughnut cells [Figure 1d]. Background showed neutrophils, macrophages, lymphocytes, apoptotic cells, mitosis, and sparse lymphoglandular bodies. Keeping in view the above findings cytological diagnosis of non-Hodgkin lymphoma with high possibility of ALCL was made.

Figure 1

(a) Round tumor cells with well defined cell borders, cytoplasmic blebs at places, pleomorphic nuclei, plasmacytoid cells and a mitotic figure (Giemsa, ×400); (b) Hallmark tumor cell (Giemsa, ×400); (c) Hand mirror cell (Giemsa, x400); (d) Doughnut cell (Giemsa, ×400)

Histologically, the sections showed ulcerated squamous epithelium. Dermis showed diffuse population of tumor cells especially arranged around blood vessels. Individual tumor cell showed round to pleomorphic nuclei with an irregular nuclear membrane and conspicuous nucleoli. Many reniform/horseshoe shaped nuclei, mitotic figures and apoptotic bodies were also seen. There was no necrosis in the biopsy tissue examined [Figure 2]. Histopathological features were suggestive of high grade non-Hodgkin lymphoma, ALCL. On immunohistochemistry (IHC), the tumor cells were positive for CD 45 and CD 30 [Figure 2, Inset] which favored the diagnosis of CD 30+ primary cutaneous anaplastic large cell lymphoma.

Figure 2

Diffuse population of tumor cells with round to pleomorphic nuclei, horse shoe shaped nuclei, mitotic figures, apoptotic bodies and part of overlying epidermis can be seen (H and E, ×400), Inset showing CD 30 positivity (IHC, ×400)

Discussion

ALCL is a nodal T-cell malignancy that is characterized by homogenous proliferation of large atypical lymphocytes that express CD 30 antigen. World Health Organisation (WHO) divides ALCL into two groups. First group includes a spectrum of CD30+ T-cell lymphoproliferative disorders that include lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. The second group is systemic ALCL. Systemic ALCL(S-ALCL) is further subdivided into anaplastic lymphoma kinase(ALK) positive and ALK negative subtypes based upon the expression of ALK. Anaplastic lymphoma kinase expression is due to t (2;5) (p23q35) translocation activating NPM-ALK protein that acts like an oncogene. Cutaneous ALCL is confined to skin and usually does not express ALK while systemic ALCL usually presents as advanced stage disease with nodal involvement and B- symptoms (mediastinal mass, spleen, liver or lung involvement). The ALK+ group of S-ALCL generally involve children and young adults having good prognosis, while ALK- S-ALCL mainly affects elderly population with bad prognosis.[16]

As an adjunct to tissue base diagnosis imprint cytology plays important role in the evaluation of lymphoid neoplasm.[7] The diagnosis of ALCL relies on recognition of various morphological features, most important is the presence of ‘hallmark cells’. The nuclei of hallmark cells is reniform, embryo like and horse shoe like with distinct nucleoli and having high mitotic activity. Small cytoplasmic blebs can be identified at the cell periphery. Other cytological variants include ‘plasmacytoid’ cells, ‘hand mirror’ cells, ‘doughnut’ cells, cells with multilobated nuclei, and multinucleated tumor giant cells with wreath like arrangement of nuclei. Neutrophil rich variant have large number of neutrophils admixed with tumor cells.[158] In the present case, the presence of characteristic hallmark cells, plamacytoid cells, cytoplasmic blebbing, doughnut cell, hand mirror cell, sparse lymphoglandular bodies, and apoptotic cells were helpful in the diagnosis on imprint cytology.

The differential diagnosis on imprint smears includes carcinoma, malignant melanoma, diffuse large B cell lymphoma and Hodgkin lymphoma. The distinction between carcinoma and C-ALCL can be difficult. High grade carcinoma can have necrosis, contain neutrophils, and dispersed cells. However, the presence of characteristic hallmark cells, lymphoglandular bodies, and cytoplasmic budding favors a diagnosis of cutaneous anaplastic large cell lymphoma.[18]

Distinguishing malignant melanoma from C-ALCL may be difficult in case of amelanotic melanoma where brown colored melanin pigment is absent. However, melanoma cells have uniform hyperchromatic nuclei, intranuclear inclusions, large prominent nucleoli, and infrequently display significant apoptosis/necrosis. Melanoma cells demonstrate nuclear positivity for S-100 protein and are negative for CD 30 and other lymphoid markers.[89]

Diffuse large B-cell lymphoma is included in the differential diagnosis but cytological hallmark cells or cell variants have not been reported.[10]

Hodgkin lymphoma rarely involves skin. The Reed Sternberg cells (R-S cells) are often identified in Hodgkin lymphoma. The R-S cells are binucleate and contain solitary inclusion like eosinophilic macronucleoli surrounded by clear chromatin. Background has lymphocytes, eosinophils, plasma cells and histiocytes. Immune marker study is helpful in differentiation.[8]

In conclusion, we think that primary cutaneous anaplastic large cell lymphoma can be diagnosed on imprint smears due to its characteristic morphological features. Imprint smears should be considered in patients presenting with ulcerative lesion of the skin. The method is rapid, easily done and a preliminary report can be given as the treatment is different for lymphoma and carcinoma. The diagnosis should be confirmed by histopathological and immunohistochemical studies.