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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 . 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 .
it can involve lymph nodes and extranodal sites including skin , soft tissue , and the gastrointestinal tract .
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 .
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 )
we describe a case of alcl mimicking a high - grade sarcoma on fna cytology .
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 .
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 .
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 )
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 ] .
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 .
mitotic figures are noted by arrows ( diff - quick stain , 400 ) smear shows a cell with a wreath - like nucleus in the center .
prominent nucleoli are noted ( papanicolaou stain , 400 ) 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 .
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 ) 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 .
immunohistochemical staining for cd30 shows strong cytoplasmic staining in the neoplastic cells ( ihc , 400 )
there are only a few case reports / series describing the cytomorphologic features of alcl on fna biopsy.[36 ] the largest series reported by rapkiewicz et al . reviewed 37 patients with alcl of which
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 .
the study concluded that although difficult , alcl can be accurately diagnosed on fna specimens when aided by ancillary studies such as ihc .
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 .
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 .