INTRODUCTION

Anaplastic large cell lymphoma (ALCL) is a non-Hodgkin’s lymphoma (NHL) characterized by a high expression of CD30 [1]. The presence or absence of anaplastic lymphoma kinase expression (ALK) subdivides it into two groups: ALCL-ALK+ and -ALK-. These differ in clinical and prognostic aspects. The primary site is most often the lymph node, and muscle localization is extremely rare [2,3]. Herein, we report a case of ALK-negative systemic LAGC with primary involvement of the skeletal muscle mimicking dermo-hypodermatitis.

CASE REPORT

A 69-year-old male with no significant pathological history was admitted for the management of dermohypodermatitis evolving for three weeks before admission. An examination revealed a warm, painful, edematous, erythematous placard taking the whole left axillary cavity and extending to the left lateral and anterior chest wall (Fig. 1a) with the presence of a homolateral axillary induration, which was suggestive of a collection at the early stage and a limitation of mobility in the left upper limb. No adenopathy or hepatosplenomegaly was noted. The patient was put on parenteral antibiotic therapy based on amoxicillin clavulanic acid and ciprofloxacin without improvement with the extension of the erythematous placard and a rise in C-reactive protein contrasting with negative procalcitonin. An ultrasound scan of soft tissues revealed a heterogeneous hypoechoic axillary mass with peripheral vascularization on Doppler, measuring 55mm in diameter, raising suspicion of an axillary tumor process. An echo-guided biopsy of the mass with a histological study revealed a widely necrotic tumor proliferation arranged in diffuse layers, made of large atypical cells with enlarged, irregular hyperchromatic nuclei and abundant cytoplasm, sometimes eosinophilic (Fig. 2a). On an immunohistochemical study, the tumor cells expressed CD30 intensely (Fig. 2b), without the expression of CD15, CD20, ALK, T markers, cytokeratin (CK), or melanin markers, evoking anaplastic large cell lymphoma of null phenotype, CD30-positive, ALK-negative. A skin biopsy was also performed and revealed no lymphomatous proliferation in the skin. A CT scan revealed an isodense mass with heterogeneous enhancement at the expense of the pectoralis minor muscle, with no individualization of suspicious adenopathies or secondary localizations (Fig. 3a). The evolution was marked by the appearance of an ulcerating left axillary tumor with the enlargement of the homolateral upper limb and the alteration of the general condition (Fig. 1b). Doppler showed deep venous thrombosis of the left axillary vein and a follow-up CT scan showed a progression of the lymphomatous disease with the invasion of the axillary vein (Fig. 3b). The patient was a candidate for chemotherapy yet died several days later probably due to a pulmonary embolism.

	Figure 1: (a) Warm, painful, edematous, erythematous placard on the left axilla. (b) Ulcerating left axillary tumor with a necrotic surface and swelling of the homolateral upper limb.
	Figure 2: (a) Tumor proliferation made of large, atypical cells with enlarged, irregular hyperchromatic nuclei and cytoplasm sometimes dropping eosinophils (H&E, 400×). (b) On the immunohistochemical study, the tumor cells expressed CD30 intensely.
	Figure 3: (a) Isodense mass of 5.5 cm in diameter with heterogeneous enhancement, depending on the pectoralis minor muscle. (b) Progression of lymphomatous disease with the invasion of the axillary vein.

DISCUSSION

ALCL ordinarily expresses T-cell phenotype, null phenotype representing only 15% of cases [4]. ALK-negative ALCL accounts for 15% to 50% of systemic LAGC and often occurs at an advanced stage of the disease. It mainly affects adults between 40 and 65 years of age, with a slight male predominance [1,5]. Nodal involvement is found in approx. 50% of cases, while extranodal involvement represents only 20% of cases. The most frequently affected sites are the skin, liver, lungs, and gastrointestinal tract [1,5].

Skeletal muscle involvement is exceptional [2] and may be primary, as in our patient, or secondary by local extension from adjacent bone or lymph node lesions [3]. Highly rare cases of primary muscular LAGC have been reported in the literature, such as the case reported by Yang et al. [2] in which the tumor was located in the psoas muscle, and the patient complained of lumbar pain resistant to analgesic treatment, and another case in the flexor muscle of the forearm reported by Chim et al. [3], whose diagnosis in both cases was confirmed by imaging and histological and immunohistochemical studies.

Skin involvement may present as solitary or multiple lesions, including papules, nodules, or tumors [1], yet sometimes may mimic other common dermatological conditions, responsible for a delay in diagnosis. In our case, the fever, the hot and painful erythematous placard, and the initial biological check-up were misleading and indicated an infection. Rare cases of dermo-hypodermatitis and cellulitis of different locations revealing ALCL or other NHL have been reported in the literature [6–9], characterized by a rapid aggravation and a lack of clinical improvement despite a well-conducted antibiotic treatment [3], as was the case in our patient. The diagnosis is based on the correlation between clinical, histological, and immunohistochemical studies and imaging findings to exclude lymph node involvement with secondary muscle involvement.

ALK-negative ALCL has an aggressive course and poor prognosis, with five-year survival rates of 30% to 49% [10]. Peripheral blood dissemination (leukemic phase) is highly rare [1]. Treatment consists of multidrug chemotherapy [1], among which CHOP is the most frequent regimen to treat systemic ALCL [5].

CONCLUSION

ALCL may have a variety of cutaneous presentations. As it is uncommon, it may be underdiagnosed, hence the interest in performing complementary investigations in front of any suspicion of malignancy in order to detect the disease at an early stage and improve the prognosis of atypical cases.