Histiocytoid Sweet’s syndrome: a histological variant

Sometimes, Sweet’s syndrome can occur in an unusual form. This is called a disease variant.

What is histiocytoid Sweet’s syndrome?

Histiocytoid Sweet’s syndrome is a rare histological variant of Sweet’s syndrome that has most commonly been associated with cancer (35-55% of cases), and medications (Morgado-Carrasco et al, 2018; Wick and Bush, 2015). In regards to the former, it normally occurs in association with a group of blood cancers called myelodysplastic syndromes (MDS) (Shalaby et al, 2016). It has also developed secondary to infections and autoimmune conditions (Morgado-Carrasco et al, 2018).

How is histiocytoid Sweet’s syndrome different from Sweet’s syndrome?

In patients with histiocytoid Sweet’s syndrome, their biopsy results show something different from what you would normally expect to find in Sweet’s syndrome.

In Sweet’s syndrome, mature white blood cells called neutrophils accumulate in the tissues. In histiocytoid Sweet’s syndrome, immature myeloperoxidase-positive cells and not mature neutrophils can be seen (mainly M2-like CD 163+macrophages) (Arima et al, 2015; Fernandez-Torres et al, 2014; Jo et al, 2012; Miller et al, 2015; Requena et al, 2005). Myeloperoxidase is an enzyme that’s abundantly expressed in neutrophils.

The immature cells in histiocytoid Sweet’s syndrome can be mistaken for histiocytes; immune cells that destroy foreign substances and help fight infection. Sometimes, real or ‘authentic histiocytes’ may also be present (Alegria-Landa et al, 2017).

What are the symptoms of histiocytoid Sweet’s syndrome?

The symptoms of histiocytoid Sweet’s syndrome and Sweet’s syndrome are the same. Read more here. 

Skin lesions are the commonest symptom of Sweet’s syndrome, and there are different lesion types. In Sept/Oct 2016, the first case of histiocytoid Sweet’s syndrome with annular or ring-shaped lesions was reported in medical literature (Macarini et al, 2016). Initially, it was thought that this particular lesion type might be a symptom of another condition such as erythema multiforme, sarcoidosis, or granuloma annulare.

How is it treated?

Histiocytoid Sweet’s syndrome is treated in the same way as Sweet’s syndrome. The most common treatment is steroid medication, e.g. prednisone, but other treatments have been used. In 2015, a female patient with histiocytoid Sweet’s syndrome was successfully treated with 50mg of azathioprine, daily (Miller et al, 2015). In 2018, the biologic drug, etanercept, was used to treat persistent Sweet’s syndrome in a 34-year-old woman (Watson et al, 2018).

Can histiocytoid Sweet’s syndrome be confused with other conditions?

Yes, histiocytoid Sweet’s syndrome can be confused with the conditions leukaemia cutis and Kikuchi-Fujoimoto disease (histiocytic necrotizing lymphadenitis), or other skin conditions that show histiocytes or histiocyte-like cells in the tissues (Macarini et al, 2016; Requena et al, 2005; Yeom et al, 2017).

Diagnostic recommendations.

Due to histiocytoid Sweet’s syndrome association with cancer and blood disorders, it’s recommended that:

  • A complete haematological assessment be given at diagnosis (Ghoufi et al, 2016).
  • Blood cell counts be monitored for at least 6 months after diagnosis.

Other information.

In both histiocytoid Sweet’s syndrome and Sweet’s syndrome, biopsy can sometimes show other types of white blood cell, e.g. lymphocytes (Morgado-Carrasco et al, 2018).

Very rarely, a patient may develop subcutaneous histiocytoid Sweet’s syndrome. The most recent case was reported in a patient with relapsed acute myeloid leukaemia (Lee et al, 2017).

References.

Alegría-Landa, V., Rodríguez-Pinilla, S., Santos-Briz, A., Rodríguez-Peralto, J., Alegre, V., Cerroni, L., Kutzner, H. and Requena, L. (2017) Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome. JAMA Dermatology, Mar 15 (PubMed).

Arima, Y., Namiki, T., Ueno, M., Kato, K., Tokoro, S., Takayama, K., Miura, K. and Yokozeki, H. (2015) Histiocytoid sweet syndrome: a novel association with relapsing polychondritis. The British Journal of Dermatology, Oct 16th (PubMed).

Fernandez-Torres, R., Castro, S., Moreno, A., Alvarez, R. and Fonseca, E. (2014) Subcutaneous histiocytoid sweet syndrome associated with crohn disease in an adolescent. Case Reports in Dermatological Medicine, March 26th (PMC).

Ghoufi, L., Ortonne, N., Ingen-Housz-Oro, S., Barhoumi, W., Begon, E., Haioun, C., Pautas, C., Beckerich, F., Robin, C., Wolkenstein, P., Cordonnier, C., Chosidow, O. and  Toma, A. (2016) Histiocytoid Sweet Syndrome Is More Frequently Associated With Myelodysplastic Syndromes Than the Classical Neutrophilic Variant: A Comparative Series of 62 Patients. Medicine (Baltimore), Apr;95(15):e3033 (PubMed).

Jo, M., Lim, Y., Shin, H., Choe, J., Seul, J. and Jang T. (2012) A Case Report of Sweet’s Syndrome with Parotitis. Archives of Plastic Surgery, Jan;39(1):59-62 (online).

Lee, J., Cornejo, K., Rork, J. Rothman, K. and Deng, A. (2017) Subcutaneous Histiocytoid Sweet Syndrome in a Patient With Relapsed Acute Myeloblastic Leukemia. The American Journal of Dermatopathology, Mar 9 (PubMed).

Marcarini, R., Araujo, R., Nóbrega, M., Medeiros, K., Gripp, A. and Maceira, J. (2016) Histiocytoid Sweet’s syndrome presenting with annular erythematous plaques. Anais Brasileiros de Dermatologia, Sep-Oct;91(5 suppl 1):154-156 (PMC).

Miller, J., Lee, N. and Sami, N. (2015) Histiocytoid Sweet syndrome treated with azathioprine: a case report. Dermatology Online Journal, Jul; 21(7).

Morgado-Carrasco, D., Moreno-Rivera, N., Fusta-Novell, X., Garcia-Herrara, A., Carrera, C. and Puig, S. (2018) Histiocytoid Sweet’s syndrome during combined therapy with BRAF and MEK inhibitors for metastatic melanoma. Melanoma Research, Jun;28(3):256-257 (PubMed). Dabrafenib and trametinib.

Requena, L., Kutzner, H., Palmedo, G., Pascual, M., Fernández-Herrera, J., Fraga, J., García-Díez, A. and Yus, E. (2005) Histiocytoid Sweet Syndrome:  A Dermal Infiltration of Immature Neutrophilic Granulocytes. JAMA Dermatology (online).

Shalaby, M., Riahi, R., Rosen, L. and Soine, E. (2016) Histiocytoid Sweet’s Syndrome in a Patient with Myelodysplastic Syndrome: Report and Review of the Literature. Dermatology Practical & Conceptual, Jan; 6(1): 9-13 (PMC).

Watson, I., Haugh, I., Gardner, A. and Menter, Martin Alan (2018) Histiocytoid Sweet syndrome successfully treated with etanercept. Baylor University Medical Center Proceedings, May 9 (Taylor & Francis Online).

Wick, M. and Bush, J. (2015) Cutaneous Histiocytoid Sweet Syndrome & its Relationship to Hematological Diseases. Journal of Cutaneous Pathology, Dec 23rd (PubMed).

Yeom, S., Ko, H., Moon, J.,  Kang, M., Byun, J., Choi, G. and Shin, J. (2017) Histiocytoid Sweet Syndrome in a Child without Underlying Systemic Disease. Annals of Dermatology, Oct;29(5):626-629 (PMC online).

2012-present, Sweet’s Syndrome UK

7 thoughts on “Histiocytoid Sweet’s syndrome: a histological variant”

  1. Dual diagnosis of histiocytoid Sweet syndrome and anti-neutrophil cytoplasmic antibody-associated vasculitis, APR 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039867/

    “Histiocytoid Sweet syndrome (H-SS) is a rare variant of acute febrile neutrophilic dermatosis. It is frequently associated with hematologic malignancies but has also been associated with certain inflammatory states. Here we report a case of concurrent anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and H-SS diagnoses.”

    “Our patient had a very rare combination of H-SS skin lesions in the setting of ANCA proteinase-3 granulomatosis with polyangiitis glomerulonephritis.”

    ANCA-ASSOCIATED VASCULITIS: Neutrophilic dermatoses, including Sweet’s syndrome, have previously been recognized in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.

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  3. New Practical Aspects of Sweet Syndrome, Feb 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853033/

    “Histiocytoid SS is characterized by the presence of immature neutrophils in the dermis that resemble histiocytes; the entity was first described by Requena et al. in 2005. Microscopic examination of histiocytoid SS reveals exuberant infiltrate of immature neutrophils; immunohistochemical staining is positive for cluster of differentiation 68 (CD68) and myeloperoxidase. Since the publication of the disease defining case series by Requena et al., over 200 cases of histiocytoid SS have been reported [60].

    In 2020, Haber et al. performed a systematic review of all published cases of histiocytoid SS to better characterize this histologic variant. The investigators reported histiocytoid SS to have a fairly equal (1.11:1) female:male ratio. They additionally noted extracutaneous involvement to be a relatively rare occurrence. Moreover, histiocytoid SS, compared with classical SS, was found to be associated with a higher risk of underlying malignancy [61].

    There has been some controversy over whether histiocytoid SS overlaps with leukemia cutis. However, in 2017 Alegría-Landa et al. performed immunohistochemical studies on 33 patients with histiocytoid SS to unequivocally show that the cells in histiocytic SS were of myeloid, not lymphoid, lineage. The study also failed to reveal histiocytoid SS being more frequently associated with malignancy compared with classical SS [62], a result inconsistent with the systematic review by Haber et al [61]. However, as malignancy-associated cases of histiocytoid SS may be overrepresented in literature due to novelty, the pooled analysis by Haber et al. may artificially create an association between malignancy and histiocytoid SS where such an association may not veritably exist [61]. Further studies are warranted to elucidate whether histiocytoid SS is more likely to be associated with malignancy than classical SS.

    It is unclear if the treatment for histiocytoid SS should differ from those for other SS variants. Several cases of histiocytoid SS have been shown to regress completely with steroid treatment [63–65], while one case of histiocytoid SS refractory to steroid therapy has been recently described [66]. Once again, larger studies of patients with histiocytoid SS would help elucidate the best treatment options for this variant.”

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  4. Pseudocarcinomatous Sweet syndrome, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343922/

    A case of the rare Sweet’s syndrome variant, pseudocarcinomatous Sweet’s syndrome. This variant may be misdiagnosed as the skin cancer, squamous cell carcinoma.

    On biopsy, pseudocarcinomatous Sweet’s syndrome can show a neutrophilic dermal infiltrate (lots of neutrophils in the dermal skin layer), and pseudoepitheliomatous hyperplasia – pronounced thickening of the skin due to proliferation of all layers of the epidermis with irregular elongation of the rete ridges/pegs (rete pegs are intermittent regular protrusions of the outermost skin layer (epidermis) into the underlying skin layer (dermis)). Pseudoepitheliomatous hyperplasia can be seen in chronic inflamed skin lesions, and mimic a well-differentiated (keratoacanthoma-type) squamous cell carcinoma.

    Biopsy won’t show certain features found in squamous cell carcinoma, such as a prominent dyskeratosis (abnormal keratinization occurring prematurely within individual cells or groups of cells below the stratum granulosum (granular layer of skin). Keratinization is a process by which keratin hardens). Keratinocyte skin cells are major building blocks of the epidermis. They make keratin, a protein that provides strength to skin, hair, and nails.

    IMP! Sufficient sample of dermis needed in order to distinguish between pseudocarcinomatous Sweet’s syndrome and squamous cell carcinoma.

    “Pseudocarcinomatous Sweet syndrome (pSS) is a rare histopathologic variant of acute febrile neutrophilic dermatosis that may clinically and histologically mimic squamous cell carcinoma (SCC).”

    “A 65-year-old female with recurrent acute myeloid leukemia (AML) treated with the FLT3 inhibitor gilteritinib presented to the emergency department with a 4-day history of worsening facial lesions, rapidly increasing in size and number.”

    “Examination revealed a large violaceous, crusted plaque on the left cheek, several smaller pinkish-purple crusted papules scattered on the cheek and left temple, and a firm subcutaneous mass with overlying ill-defined erythema on the left upper chest. Of note, 1 month prior she was admitted with fever and submandibular erythema and edema, diagnosed as possible differentiation syndrome secondary to gilteritinib, although she did not have enough clinical features to establish the diagnosis. She improved with a 3-week oral dexamethasone taper, which ended 13 days prior to this presentation. When these new facial lesions appeared, oncology admitted her to the hospital for IV dexamethasone and consulted inpatient teledermatology service.”

    “Punch biopsies from the left cheek revealed complex epidermal hyperplasia, initially interpreted as SCC by general pathology. On reevaluation by dermatopathology, a neutrophilic dermal infiltrate with a differential of infectious process versus pSS was diagnosed.”

    “Approximately 20% of all SS cases are associated with malignancy, most commonly AML. pSS is a rare subtype of SS characterized by pseudoepitheliomatous epidermal hyperplasia (PEH). To our knowledge, only 1 other case of pSS has been reported.”

    “Pseudocarcinomatous hyperplasia is a reactive epidermal hyperplasia characterized by elongated, thickened, and broad rete ridges. It is generally associated with infection (especially deep fungal infection), chronic inflammation, hypersensitivity reactions, and malignancy. Histologically, PEH may closely resemble SCC, especially in biopsy specimens with insufficient dermis. However, unlike SCC, the pathology of pSS lacks nuclear atypia, abundant or abnormal mitoses, and prominent dyskeratosis. Clinicopathological correlation is important in differentiaPEH from SCC.”

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  6. Click on ‘Med J Malaysia’ to access free full-text PDF. https://pubmed.ncbi.nlm.nih.gov/36448383/

    Sweet’s syndrome: A review from two tertiary hospitals in Malaysia, 2022.

    Screening for underlying cancer is essential especially for SS patients who present with anaemia, low platelets, and pathergy phenomenon (where skin damage, most commonly minor damage, triggers the development of skin lesions). Mycobacterial infection should be considered in this region due to high tuberculosis burden.

    Studies have showed that fluorescence in situ hybridisation (FISH) analysis of the cells in the skin may help to distinguish between histiocytoid SS and leukaemia cutis.

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