Lymphoplasmacytic plaque in children: a report of two new cases with review of the literature

Abstract

Lymphoplasmacytic plaque in children has been proposed as a rare, emerging clinicopathologic entity characterized by solitary, extratruncal, asymptomatic papules and plaques that are typically found in healthy young Caucasian females. Biopsy of these lesions reveals a dermal lymphoplasmacytic infiltrate with or without epithelioid granulomas. Two unique patients with lymphoplasmacytic plaque in children are presented in this report, including a 26-month-old female with a lesion on her finger, who represents both the youngest described patient and the first documented with a finger lesion, as well as a 17-year-old young woman with a left thigh lesion, who represents the patient with the longest clinically and histopathologically observed lesion to date. These two additional patients corroborate the experience of lymphoplasmacytic plaque in children in the six previously reported cases and further expand the clinicopathologic spectrum of the disease. Recognition of lymphoplasmacytic plaque in children is important to facilitate distinction from potential differential considerations, including lymphoproliferative disorders and infectious conditions, particularly as the experience to date appears to suggest that lymphoplasmacytic plaque in children represent a reactive (pseudolymphomatous) condition.

‘Pretibial lymphoplasmacytic plaque in children’ was the term recently proposed for an emerging clinicopathologic entity by Fried et al.[1] On the basis of the six reported cases to date, affected patients are typically healthy Caucasian girls or adolescents with a solitary extratruncal plaque or papules. In each reported case, the plaque had typically been stable and asymptomatic. A dermal lymphoplasmacytic infiltrate, with or without epithelioid granulomas, is noted histopathologically. Significantly, no hypergammaglobulinemia, lymphadenopathy or hepatosplenomegaly has been reported in these patients. Presented herein are two patients who show clinical and histopathologic features that both corroborate the previous characterization of this condition as a pseudolymphomatous state, expand its clinicopathologic spectrum to lesions occurring on the thigh and digits and document lesions occurring in younger children, thereby lending support to adoption of the broader term ‘lymphoplasmacytic plaque in children’.

Report of patients

Patient 1

A 17-year-old otherwise healthy Caucasian young woman presented with a slowly enlarging plaque on the left thigh of more than 10 years duration. She had first presented with this plaque 5 years previously and had had a biopsy revealing plasmacytic and granulomatous dermatitis (Fig. 1A,B). Since that point there had been minimal interval change in clinical appearance. The lesion had been asymptomatic aside from occasional tenderness when dressing. She denied any history of trauma or foreign body exposure. The patient's medical history and review of systems were otherwise unremarkable.

Figure 1. A) Initial skin punch biopsy of patient #1 demonstrating dense, chronic and granulomatous inflammatory infiltrate in lichenoid arrangement extending in inverted wedge-shaped pattern into the deep dermis [H&E; 40x]. B) Higher magnification revealing the infiltrate to be composed of predominantly lymphocytes and plasma cells [H&E; 400x].

Examination revealed firm pink papules coalescing into a somewhat serpiginous 2 cm plaque on the patient's left thigh (Fig. 2). The lesion was slightly erythematous and non-tender to palpation. No lymphadenopathy was appreciated. There were no other primary skin lesions on examination.

Figure 2. Irregularly grouped, coalescent small erythematous papules on the left thigh of patient #1.

Histopathologic examination of a skin punch biopsy revealed a dense, nodular and lichenoid inflammatory infiltrate occupying the upper dermis with extension perivascularly into the deep dermis (Fig. 3A,B). The infiltrate consisted predominantly of lymphocytes, prominent admixed plasma cells and histiocytes forming small epithelioid granulomas. Occasional dilated small blood vessels were noted within the superficial dermis. No birefringent foreign material was detected on polariscopic examination. No microorganisms were identified on Grocott's methenamine silver, acid fast bacilli and Warthin–Starry stains. Subsequent re-excision of the lesion was performed, showing similar histopathologic features (Fig. 4A,B). Polyclonality was confirmed by co-existence of kappa and lambda light chain positive cells by immunohistochemical studies.

Figure 3. A) Second skin punch biopsy of patient #1 demonstrating a dense, lichenoid chronic inflammatory infiltrate [H&E; 100x]. B) Higher magnification highlighting the largely lymphocytic and plasmacytic nature of the infiltrate [H&E; 600x].

Figure 4. A) Excision specimen from patient #1 showing similar dense, chronic inflammatory infiltrate of the upper dermis [H&E; 100x]. B) Higher magnification featuring small lymphocytes and plasma cells associated with small slender blood vessels [H&E; 400x].

Follow up with the patient 11 months post excision revealed no residual or recurrent lesion at the excision site and the patient continues to be asymptomatic without skin complaints or other concerns.

Patient 2

A 26-month-old healthy Caucasian girl presented with her mother, who complained of a ‘red bump’ on her child's left third finger. The lesion was first noticed 2 weeks after birth and at that time was reportedly smaller and flat. At 20 months of age, the patient's mother noted that the lesion had enlarged, become raised and at times would become irritated and tender. The patient's mother had observed the patient biting the lesion on several occasions. The child's medical history and review of systems were unremarkable except for an appendectomy at age two. The patient's mother denied any other known trauma or foreign body exposure.

On examination, the patient showed an 8 mm erythematous, smooth papule with slight scaling on the dorsal surface of the left third finger near the proximal interphalangeal joint. Dermatologic examination revealed no other rashes. A shave biopsy was performed, showing a brisk, lichenoid lymphoplasmacytic infiltrate obscuring the dermal–epidermal junctional interface with overlying parakeratosis and irregular epidermal hyperplasia featuring basilar squamotization with ‘saw-tooth’ rete and dyskeratosis (Fig. 5). Immunohistochemical studies showed the co-existence of kappa and lambda light chain positive cells, confirming polyclonality. No organisms were identified on a Warthin–Starry stain. Acid fast bacilli and Giemsa stains were unrevealing.

Figure 5. Shave skin biopsy of patient #2 showing a brisk lymphoplasmacytic infiltrate arranged in lichenoid fashion obscuring the dermal-epidermal junction with attendant basilar squamatization [H&E; 250x].

Of note, while lichen striatus was entertained as a diagnostic possibility in this patient, the lack of clear blaschkoid distribution to the lesion, the lack of nail involvement despite the lesion's location on the distal finger and the lesion's persistence for more than 2 years clinically, in conjunction with the prominent plasmacellularity seen on biopsy spoke against lichen striatus as the likely diagnosis.

Three months after shave biopsy was performed, a residual papule remained at the site. Examination revealed a clinically unchanged smooth erythematous 8-mm papule with a central linear scar at the shave biopsy site (Fig. 6). The patient's mother has elected to observe the lesion at this point, as she weighs options for further management.

Figure 6. Persistent 8 mm smooth erythematous papule with biopsy scar near the PIP of the left middle finger of patient #2.

Discussion

Lymphoplasmacytic plaque in children represents an emerging diagnosis whose clinicopathologic characterization continues to evolve. Born of the recognition that indolent, localized plaques exhibiting a prominent lymphoplasmacytic infiltrate can occur in children lacking evidence of systemic involvement, lymphoplasmacytic plaque was originally termed ‘isolated benign primary cutaneous plasmacytosis in children’ by Gilliam et al.[2] In retrospect, however, a patient who also likely would meet criteria for this condition had been previously reported under the label of ‘primary cutaneous plasmacytosis in a child’, distinct from the classic primary cutaneous plasmcytosis seen in adults with many systemic symptoms.[3] Gilliam et al.[2] acknowledged this and reported two additional healthy young patients with plasmacytic plaques overlying the tibia. A subsequent patient with similar features was then documented by Fried et al.[1] who in their analysis suggested the term ‘pretibial lymphoplasmacytic plaque in children’ to emphasize the absence of systemic plasmacytosis in these individuals. Since these reports, two additional patients have been reported in the literature (Table 1), including one 7-year-old Asian girl whose lesion arose on the buttock[4] and a 9-year-old girl with a pretibial lesion exhibiting the epithelioid granulomatous component on histopathology.[5]

Table 1. Reported cases of lymphoplasmacytic plaque in children

	Age (years)	Gender	Ethnicity	Location	Morphology	Duration by history (years)	Hematoxylin–eosin staining	Clinical course/treatment
* Five years confirmed clinically and histopathologically.
Aricò and Bongiorno[3]	7	F	Caucasian	Trunk	10 cm plaque with red–brown papules	4	Dermal lymphoplasmacytic infiltrate	Intermittent treatment with topical corticosteroids was unsuccessful
Gilliam et al.[2]	15	F	Caucasian	Pretibial	4.5 cm red–brown violaceous plaque	11	Dermal lymphoplasmacytic infiltrate	Pulse-dye laser was used to diminish the color of the lesion
	7	M	Caucasian	Pretibial	Several centimeters scaled violaceous papulonodules	2	Dermal lymphoplasmacytic infiltrate	N/A
Fried et al.[1]	11	F	Caucasian	Pretibial	4 cm red–brown plaque	5	Dermal lymphoplasmacytic infiltrate ± small granulomas	Partial, short-term remission was achieved with intralesional steroid injection
Ahn et al.[4]	7	F	Asian	Buttock	3 cm erythematous scaly plaque	7	Dermal lymphoplasmacytic infiltrate	Partial remission was achieved with a combination of tapered prednisolone, intralesional steroids and topical steroids. Excision was eventually performed
Moulonguet et al.[5]	9	F	Caucasian	Pretibial	3.5 cm red–brown plaque	5	Dermal lymphoplasmacytic infiltrate ± epithelioid granulomas	Local and topical steroids resulted in slight improvement
Present report	17	F	Caucasian	Thigh	2 cm pink serpiginous plaque	>10*	Lichenoid dermal lymphoplasmacytic infiltrate with small epithelioid granulomas	The lesion was excised and the patient was recurrence free at 11 months
	2 years and 2 months	F	Caucasian	3rd Finger	8 mm erythematous scaled papule	2 years and 6 weeks	Lichenoid dermal lymphoplasmacytic infiltrate	The patient's family has elected to observe the lesion while weighing options for further management

Clinically, lymphoplasmacytic plaque in children is characterized by minimally symptomatic, solitary, pink to violaceous erythematous papulonodular plaques up to a few centimeters in dimension with a variably smooth to lobulated surface, and variable scaling. Affected individuals to date have ranged from age 7 to 15, with predilection for females. As indicated by the earlier term pretibial lymphoplasmacytic plaque, the anterior shins appear the favored site; however, more recent experience has showed occurrence of lesions at other locations, including the buttock. This clinical picture can raise differential consideration for vascular lesions, spitzoid proliferations, histiocytic tumors, infectious processes or lichenoid conditions. Significantly, none of these individuals evidenced any signs of systemic involvement related to their lymphocytic plaques, and all the patients accordingly have experienced a favorable course, with treatment for the lesions including observation, topical steroids and excision.

Histopathologically, lymphoplasmacytic plaque shows a dense, mixed infiltrate featuring lymphocytes with admixed plasma cells. Recent reports have highlighted that an epithelioid granulomatous infiltrate can also be seen. Additionally, some lesions have been noted to exhibit a strikingly lichenoid pattern. The presence of variably robust lymphocytic and plasmacytic populations can raise suspicion for a primary lymphoproliferative disorder or for an infectious process. With regard to the former category, particular differential consideration can be given to cutaneous plasmacytoma, primary cutaneous plasmacytosis, end-stage multiple myeloma or marginal zone B-cell lymphoma. In contrast to this group of disorders, lymphoplasmacytic plaque in children does not feature lymphoid or plasmacytic atypia, and clonality has not been showed. With respect to the latter category of infectious disease, syphilis and other treponemal diseases need to be excluded by appropriate clinical and serologic evaluation. The presence of a granulomatous infiltrate obliges work-up for mycobacterial or deep fungal infection. Additional possible conditions which may enter into the pathologic differential diagnosis of lymphoplasmacytic plaque include nodular amyloidosis and even Kaposi's sarcoma.

Consideration of the pathologic differential possibilities that are raised by the histopathologic features of lymphoplasmacytic plaque in children not only highlights the importance of distinction of indolent lymphoplasmacytic plaque from potentially aggressive alternatives but also offers intriguing insight into the possible nosologic position of the entity on the continuum of lymphoid–plasmacytic disorders. Primary cutaneous plasmacytosis, in particular, represents a significant entity with overlapping and contrasting features with lymphoplasmacytic plaque. Primary cutaneous plasmacytosis typically presents as multiple truncal red–brown plaques in Asian individuals with onset in adulthood and typically with associated hypergammaglobulinemia. Furthermore, patients with primary cutaneous plasmacytosis often have lymphadenopathy, hepatosplenomegaly and an elevated erythrocyte sedimentation rate,[6] features not found in lymphoplasmacytic plaque. One additional entity meriting consideration in the differential diagnosis of lymphoplasmacytic plaque is acral pseudolymphomatous angiokeratoma of children (APACHE). APACHE is a rare clinical entity characterized clinically by multiple unilateral angiomatous papules located on hands and feet of children and microscopically by a lymphoplasmacytic infiltrate with long, thick-walled blood vessels and prominent endothelial cells. Given the observation that some reported patients with APACHE clinically and microscopically appear to closely resemble patients with lymphoplasmacytic plaque. Moulonguet et al. suggested that these disease entities may both reside on the spectrum of pseudolymphoma.[5]

The two patients presented here, representing the seventh and eighth cases of lymphoplasmacytic plaque reported to date, offer an additional experience with this provisional entity and support the conclusion that this condition may represent a pseudolymphomatous state. Both the patients detailed here appear to fulfill criteria for a diagnosis of a lymphoplasmacytic plaque while at the same time showing novel, previously undocumented features. To our knowledge, patient 1 is the first to show stability, clinically and histopathologically, for greater than 5 years. In addition, the localization of the plaque on the thigh in the case of patient 1 and on the finger in the case of patient 2, rather than in the pretibial area, is unique (Table 1). These two patients further corroborate previous observations that these plaques arise in childhood, often in Caucasian females, and are extratruncal, solitary and asymptomatic. To our knowledge, these two patients are the oldest and youngest reported with lymphomplasmacytic plaque, respectively. Histopathologically, these cases are consistent with past reports of a dermal polyclonal lymphoplasmacytic infiltrate. The biopsy in the case of patient 1 is also notable histopathologically for the presence of small epithelioid granulomas, a finding that was only also reported by Fried et al.[1] and Moulonguet et al.[5] The fact that patient 1 developed a lesion that was stable in size for over 10 years supports the conclusion that conservative therapy is appropriate for these lesions. Additional investigation is necessary to answer why this indolent condition occurs in childhood and thereby elaborate where on the lymphoplasmacytic spectrum lymphoplasmacytic plaque of children truly exists.