Neutrophil-Rich Variant of Systemic Anaplastic Large-Cell Lymphoma Masquerading as Sweet’s Syndrome

Dear Editor, Anaplastic large-cell lymphoma (ALCL) is a distinct T-cell non-Hodgkin lymphoma characterized by proliferation of large anaplastic lymphoid cells expressing CD30. It is classified into systemic ALCL (Anaplastic lymphoma kinase (ALK)-positive and ALK-negative) and primary cutaneous ALCL. Systemic ALCL typically presents with lymphadenopathy, B symptoms, and extranodal involvement, including skin, bone, liver, and lung.[1] Among its histopathologic variants, the neutrophil-rich subtype is exceedingly rare, accounting for <2% of ALCL cases, and is diagnostically challenging as atypical lymphoid cells are often obscured by neutrophils.[2] We report a rare case where neutrophil-rich ALK-negative systemic ALCL presented as Sweet’s syndrome, both clinically and histopathologically. A 19-year-old female presented with multiple painful erythematous lesions in the left groin of two weeks’ duration, rapidly progressing to pustules and crusted ulcers. She reported a 5-month history of intermittent fever with left inguinal swelling. Dermatological examination showed multiple erythematous papules, nodules, and pustules extending from the left groin to the left thigh [Figure 1a, 1b].Figure 1: (a and b) Clinical image of the left thigh showing initial presentation of erythematous papules and pustules with crusting. (c) Histopathology of skin lesion showing dense dermal infiltration by neutrophils without evidence of vasculitis (Hematoxylin and eosin, 40×)On investigation, her hemoglobin was 8.5 g/dL, total leucocyte count was 68,400 cells/uL, with 91% neutrophils, and thrombocytosis. The erythrocyte sedimentation rate was 80 mm/hr, and C-reactive protein was 253 mg/L. Peripheral smear showed neutrophilic leukocytosis. A comprehensive fever evaluation, including blood and wound cultures, smear for acid-fast bacilli, cartridge-based nucleic acid amplification test (CBNAAT), potassium hydroxide (KOH) mount, and fungal cultures, yielded negative results. Antinuclear antibody (ANA) showed weak positivity; perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) were negative. Ultrasound of the left groin revealed multiple hypoechoic lymph nodes. Fine needle aspiration cytology revealed inflammatory changes. Left inguinal lymph node biopsy was suggestive of reactive lymphadenitis. Skin biopsy from the left thigh revealed neutrophilic exocytosis without vasculitis, consistent with neutrophilic dermatosis [Figure 1c]. With two major and two minor criteria satisfied, a diagnosis of Sweet’s syndrome was made, and she was started on intramuscular dexamethasone (8 mg once daily) and oral potassium iodide (300 mg thrice daily). Despite one week of therapy, lesions worsened [Figure 2a], and the patient developed a painful left submandibular swelling. Neck ultrasonography revealed submandibular adenitis with cervical necrotic lymphadenopathy. Abdominal ultrasonography showed splenomegaly. Serum lactate dehydrogenase (LDH) was elevated (601 IU/L), serum uric acid was 1.6 mg/dL, and direct Coombs test was negative.Figure 2: (a) Clinical photograph of the left thigh showing worsening of lesions. (b) Histopathological section showing key features- large atypical lymphoid cells with moderate eosinophilic cytoplasm, pleomorphic vesicular nuclei, prominent eosinophilic nucleoli (black arrow), classical hallmark or reniform cell characteristic of anaplastic large-cell lymphoma (blue arrow), plump endothelial cells, indicating vascular proliferation (yellow arrow) (Hematoxylin and eosin, 40×)Although neutrophilic leukocytosis is typical of Sweet’s syndrome, the total leucocyte count of 68,400 cells/μL was high for classic Sweet’s, prompting consideration of other underlying causes. Repeat skin biopsy with immunohistochemistry (IHC) revealed neutrophilic microabscesses, intraepidermal lymphocytes, and dermal lymphoplasmacytic infiltrates with atypical lymphoid cells having a high nucleus cytoplasmic ratio, hyperchromatic nuclei, and eosinophilic nucleoli [Figure 2b]. IHC showed CD30+, CD3+, MUM1+, EMA+, ALK–, PAX5–, CK–, HMB45– [Figure 3a, 3b, 3c, 3d], consistent with neutrophil-rich ALK-negative systemic ALCL. Positron emission tomography–computed tomography (PET-CT) demonstrated widespread supra- and infra-diaphragmatic lymphadenopathy with involvement of skin, spleen, and bone. A final diagnosis of stage IV neutrophil-rich ALK-negative systemic ALCL was made. Unfortunately, the patient succumbed before definitive oncologic therapy could be initiated.[1]Figure 3: (a) Immunohistochemistry showing CD30 positivity, (b) CD3 positivity, (c) Epithelial membrane antigen (EMA) positivity, (d) Multiple myeloma oncogene-1 (MUM1) positivityNeutrophil-rich ALCL is extremely rare, with only sporadic cases reported.[2] It usually presents as tumorous or nodular lesions and has been reported to mimic cellulitis, panniculitis, or pyoderma gangrenosum.[3] In most cases, although histopathology suggested a neutrophilic dermatosis, clinical suspicion of malignancy persisted due to nodular lesions. However, in our case, the presentation uniquely mimicked Sweet’s syndrome both clinically and histologically. The patient fulfilled two major (abrupt onset of tender erythematous papules, nodules, pustules and predominantly neutrophilic dermal infiltrate in the absence of leukocytoclastic vasculitis in the initial biopsy) and two minor criteria (fever, abnormal laboratory values of erythrocyte sedimentation rate, C-reactive protein, total leucocyte count and neutrophils with values as mentioned earlier) for Sweet’s syndrome, and initial treatment was accordingly initiated, but poor steroid response and systemic deterioration necessitated reevaluation.[4] Other clinical differential diagnoses considered were pustular pyoderma gangrenosum (but the patient did not fulfill the diagnostic criteria), necrotizing fasciitis (ruled out by negative pus culture and absence of crepitus on clinical examination), cutaneous tuberculosis (excluded by negative acid-fast bacilli smear and negative CBNAAT results), Sweet’s like bacterial and deep fungal infections (ruled out by negative culture). The differentiation from paraneoplastic Sweet’s syndrome is essential. In paraneoplastic Sweet, skin lesions are reactive, whereas in our patient, skin was directly infiltrated by lymphoma cells, confirmed on repeat biopsy and IHC.[5] The dense neutrophilic infiltrate in this lymphoma variant may result from tumor-cell overexpression of interleukin-8 (IL-8), a potent chemotactic factor that recruits and activates neutrophils, thereby obscuring the underlying atypical lymphoid cells. This case emphasizes the aggressive potential of neutrophil-rich systemic ALCL, particularly the ALK-negative subtype, which generally carries a poor prognosis. In conclusion, this case adds to the spectrum of neutrophil-rich ALCL and underscores the diagnostic complexity posed by it, particularly when it masquerades as Sweet’s syndrome both clinically and histopathologically. Recognizing this rare presentation broadens the differential diagnosis of acute febrile neutrophilic dermatoses and reinforces the need for vigilance to avoid misdiagnosis and ensure timely initiation of appropriate oncologic therapy. Authors’ contributions All authors confirm that they have read and approved the final version of the manuscript. The manuscript represents original and honest work, and all authors take full responsibility for the integrity of its content. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.