QUIZ SECTION

Painless Red Nodule on the Right Cheek of a Young Woman: A Quiz

Matiar MADANCHI¹, Maximilian K. QUOSS¹ and Beda MÜHLEISEN^1,2

¹Department of Dermatology, University Hospital of Basel, Burgfelderstrasse 101, CH-4055 Basel and ²Department of Dermatology, Dermatopathology Training Center, University Hospital of Basel, Basel, Switzerland. E-mail: matiar.madanchi@usb.ch

 

 

A 45-year-old woman presented with an erythematous nodule on her right cheek since 3 months. She reported that the skin lesion manifested suddenly with the appearance of a small painless erythematous papule, which enlarged slowly. The patient was in good general health with no underlying diseases. She was not taking any regular medication, and denied fever, recent infections or insect bites. There was no family history of skin cancer.

Clinical examination revealed a circular erythematous nodule 0.5 cm in diameter (Fig. 1A), which was moveable on palpation. Dermoscopy revealed a vascular pattern characterized by an orange-pink background with overlying serpiginous blood vessels (Fig. 1B). There was no lymphadenopathy. Blood tests (haemogram and general blood chemistry) were normal. A punch excision of the entire lesion was performed.

Fig. 1. Clinical presentation. (A) A solitary erythematous nodule 0.5 cm diameter on the right cheek. (B) Dermoscopy revealing a well-vascularized nodule characterized by an orange-pink background with overlying serpiginous blood vessels.

What is your diagnosis?

Differential diagnosis 1: Primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder

Differential diagnosis 2: Amelanotic melanoma

Differential diagnosis 3: Dermal naevus

Differential diagnosis 4: Merkel cell carcinoma

See next page for answer.

ANSWERS TO QUIZ

Painless Red Nodule on the Right Cheek of a Young Woman: A Commentary

Diagnosis: Primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder

Punch biopsy revealed a dense dermal infiltrate of small- to medium-sized slightly pleomorphic CD4⁺ lymphocytes with increased proliferative activity (20% MiB1-positive cells) without epidermotropism. The cells were immunoreactive for PD-1 and ICOS. There was no increase in CD30 expression and a balanced ratio of kappa/lambda light chain immunoexpression (1:1). PCR revealed a biclonal rearrangement of the T-cell receptor gene yielding 2 clones of 232-bp (type V-II) and 240-bp (type III) length (Fig. 2). These findings allowed a diagnosis of a primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder to be established. The punch excision wound healed spontaneously. At subsequent follow-ups there were no signs of recurrence.

Fig. 2. Histology revealed a dense non-epidermotropic dermal infiltrate (A) (HE staining, 40x magnification) of small to medium sized slightly pleomorphic lymphocytes (B) (HE, 250x) with increased proliferative activity (20% MiB1-positive cells) (C) (250x). The tumor cells were immunoreactive for CD4 (D) (250x) but not for CD8 (E)(250x) or CD20 (F) (250x). The tumor cells expressed PD-1 (G) (250x) and ICOS (H) (250x). There was a balanced ratio (1:1) of kappa (brown) / lambda (red) light chain immunexpression (I) (250x) in the group of CD20+ B-lymphocytes and there was no increase in CD30 expression (J) (250x).

Primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a provisional entity within the spectrum of primary cutaneous T-cell lymphomas (1). The WHO revised and updated the classification of lymphoid neoplasms in 2016, and primary cutaneous CD4⁺ small- to medium-sized T-cell lymphoma was reclassified as primary cutaneous CD4⁺ small- to medium-sized T-cell lymphoproliferative disorder (PCSMLPD) (1). PCSMLPD is generally considered to be a low-grade lymphoma, meaning that it has a relatively slow growth rate and tends to be limited to the skin (2).

The exact cause and pathogenesis of PCSMLPD is not fully understood. This disorder most commonly affects middle-aged adults (women > men) (3).

PCSMLPD usually presents as 1 or more red/purple skin nodules. The most commonly affected body regions are the head and/or neck, but the trunk or limbs may also be affected (2).

Diagnosis of PCSMLPD involves a combination of clinical examination, imaging studies and biopsy of the affected skin. Histologically, PCSMLPD shows an infiltrate composed mainly of small- to medium-sized slightly pleomorphic lymphocytes, and the percentage of any large atypical cells is <30% (4). Some plasma cells, eosinophils, and histiocytes may also be present. The dermal infiltrate may have a nodular or band distribution and, as in the current case, a border zone separating it from the epidermis. Occasionally, epidermotropism or extension into the subcutaneous fat tissue may also occur (4–6).

Treatment for PCSMLPD depends on the extent and severity of the disease. Localized lesions can be treated with surgery (7), radiation therapy (8), topical steroids (2) or topical chemotherapy (7). Systemic therapy, such as chemotherapy or immunotherapy, may be used for more extensive disease (7). The prognosis for PCSMLPD is generally favourable, with most patients experiencing long-term remission after treatment. However, there is a risk of recurrence; hence, close monitoring and follow-up care are important (9).

REFERENCES

1. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375–2390.
2. Beltzung F, Ortonne N, Pelletier L, Beylot-Barry M, Ingen-Housz-Oro S, Franck F, et al. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders: a clinical, pathologic, and molecular study of 60 cases presenting with a single lesion: a multicenter study of the French Cutaneous Lymphoma Study Group. Am J Surg Pathol 2020; 44: 862–872.
3. Kempf W, Rozati S, Kerl K, French LE, Dummer R. Cutaneous peripheral T-cell lymphomas, unspecified/NOS and rare subtypes: a heterogeneous group of challenging cutaneous lymphomas. G Ital Dermatol Venereol 2012; 147: 553–562.
4. Ally MS, Robson A. A review of the solitary cutaneous T-cell lymphomas. J Cutan Pathol 2014; 41: 703–714.
5. Lan TT, Brown NA, Hristov AC. Controversies and considerations in the diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoma. Arch Pathol Lab Med 2014; 138: 1307–1318.
6. Beltraminelli H, Leinweber B, Kerl H, Cerroni L. Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases. Am J Dermatopathol 2009; 31: 317–322.
7. James E, Sokhn JG, Gibson JF, Carlson K, Subtil A, Girardi M, et al. CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma: a retrospective case series and review of literature. Leuk Lymphoma 2015; 56: 951–957.
8. Topal IO, Goncu EK, Ozekinci S, Ayaz G, Aksaray F. Primary cutaneous CD4(+) small/medium-sized T-cell lymphoma of the face: successful treatment with radiation therapy. J Dtsch Dermatol Ges 2016; 14: 522–524.
9. Gru AA, Wick MR, Eid M. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder-clinical and histopathologic features, differential diagnosis, and treatment. Semin Cutan Med Surg 2018; 37: 39–48.