Idiopathic cutaneous pseudolymphoma: An enigma.

Sir,

Pseudolymphoma is not a specific disease but an inflammatory response to known or unknown stimuli that results in a lymphomatous-appearing picture, mimicking lymphoma but in fact a benign accumulation of inflammatory cells. However, the terminology of pseudolymphoma should be reserved for idiopathic cases where inciting cause is unknown. The enigma stems from the fact that the condition has to be differentiated from cutaneous lymphoma which would change the outcome of the disease.

This case presented as a pigmented nodule just above left ala of nose since 2 years resembling a nevus in a middle-aged male which was asymptomatic [Figure 1]. The patient gave a history of recent increase in size since 2 months with no pain, discharge, and itching. On examination, it was a firm red-brown nodule, non-tender with no regional lymph nodes palpable. There was no history of insect bite, trauma, and infection at that site in the past. There was no history of drug ingestion. A wide excision was done; the histopathology was reported as cutaneous pseudolymphoma. At 6-month follow-up, patient was asymptomatic. Immunohistochemistry revealed negative CD3, CD10, leucocyte common antigen (LCA), and CD20 panel, which are markers for lymphoma. After ruling out all etiological factors mentioned above and the histological evidence of top heavy dermal, mixed cellular infiltrate, absence of pigmentation and blast cells, with no necrotic areas, it was labeled as idiopathic pseudolymphoma.

Figure 1

Nodular lesion over left ala of nose

Pseudolymphoma, also called as cutaneous lymphoid hyperplasia, is a skin lesion having lymphomatous appearance mimicking lymphoma that results from known or unknown stimulus like insect bites, vaccination, trauma, folliculitis, drugs, jewelry, and contactants.[12] This results in accumulation of inflammatory cells that not only mimics lymphoma histologically but clinically as well. Nodular lesions resemble B-cell lymphomas, whereas plaque forms resemble T-cell lymphomas. It is essential to differentiate pseudolymphomas from malignant lymphomas, which involves clinical, histological, and immunohistochemistry evidences as even in benign lesions, malignant histological picture may be seen.

Pseudolymphomas are classified according to histological components into B-cell and T-cell variants. Commonly occurring etiological causes have been tabulated along with salient histological features [Table 1]. Cutaneous lymphomas are classified according to EORTC classification.[3]

Table 1

Classification of cutaneous pseudolymphomas

Immunohistochemistry[4] forms the mainstay of differentiation in a rural setup where advanced laboratory techniques are unavailable. Minimum immunohistochemistry for any suspected hematolymphoid lesion is CD10, LCA, CD20, and CD3. CD20 is for B-cell expression, CD3 for T-cell expression and T cell germinal center, and CD10 for B-cell germinal center. In this case, CD3, CD10, LCA, and CD20 were negative, thus suggesting benign nature of the lesion [Figure 2a–d]. Techniques such as immunophenotyping staining patterns are done to diagnose lymphomas.[5]

Figure 2

×40 Immunohistochemistry stains using LCA, CD3, CD10, CD20 antibodies. (a) Leucocyte common antigen shows positivity for lymphocytes indicating predominant lymphocytic lesion (b) CD3 shows positivity for T cells but the larger cells are negative for the stain (c) CD10 shows positivity for B cells (d) CD20 shows Positivity for B cells. The larger cells are negative for the stains

The diagnosis poses a challenge more to pathologists, as the pattern of mixed infiltrate that includes histiocytes, eosinophils, and plasma cells is significant. Polymorphous infiltrates, lack of atypical lymphocytes, and dominant lymphocytic clones are highly suggestive of pseudolymphomas[6] [Figure 3]. The infiltrate tends to be “top-heavy,” in pseudolymphomas, whereas in most lymphomas, they are centered in the deep dermis. The LCA also forms a major source of differentiation, as it is negative in pseudolymphomas and strongly positive in lymphomas.

Figure 3

(a) top heavy infiltrate rich in small T lymphocytes with admixed, scattered T and B immunoblasts, histiocytes, and plasma cells. (H and E, ×10) (b) High-power field showing mixed infiltrate of T and B cells, histiocytes, and plasma cells (H and E, ×40)

In conclusion, pseudolymphomas form a diagnostic challenge in rural medical college hospital with limited resources for advanced investigations. A proper history to rule out etiology, careful histological evaluation along with judicious immunohistochemistry panel suffices, to diagnose pseudolymphomas. In many cases, a proper etiology may not be elicitable leading to labelling these cases idiopathic.[78] A follow-up of at least 5 years is required to rule out risk of cutaneous lymphomas.