T-Cell-Rich Angiomatoid Polypoid Pseudolymphoma: A Case Report and Comparison With Key Differential Diagnoses

T-cell-rich angiomatoid polypoid pseudolymphoma (TRAPP) is a rare and recently defined entity, conceptualized just over a decade ago. Recognition of TRAPP is important because it can be clinically and microscopically confused with low-grade cutaneous lymphomas and other vascular proliferations. We report a case of a 28-year-old male with a solitary 1.2 cm red polypoid papule on the middle posterior base of the neck. The histopathological examination revealed a well-circumscribed dermal nodular proliferation of banal-appearing lymphovascular spaces with plump endothelial cells. Immunohistochemical analysis showed a T-cell-rich infiltrate. The clinical-pathological differential diagnosis for TRAPP includes pyogenic granuloma, angiolymphoid hyperplasia (epithelioid hemangioma), acral pseudolymphomatous angiokeratoma of children, cutaneous lymphoid hyperplasia, and low-grade cutaneous lymphomas and lymphoproliferative disorders. We review the literature and discuss the key differentiating features between TRAPP and its common differential diagnoses.


Introduction
T-cell-rich angiomatoid polypoid pseudolymphoma (TRAPP) is a rare cutaneous vascular proliferation that presents as a solitary polypoid papule mainly on the head and neck of adults, with a slight female predominance [1,2]. In contrast to low-grade lymphomas or other cutaneous vascular neoplasms, most literature characterizes TRAPP as a solitary, exophytic erythematous papule with a striking dermal-based Tcell-rich lymphocytic infiltrate and prominent vessels lined by plump endothelial cells [1,3]. Herein, we report an additional case of TRAPP with a review of the literature and comparison to entities in the clinical and histopathological differential diagnoses.

Case Presentation
A 28-year-old male with no known relevant past medical history presented to his family physician for evaluation of a 1.2 cm red polypoid plaque on the middle posterior base of the neck. Shave excision was completed, and the specimen was submitted to dermatopathology with the differential diagnosis of hemangioma.
The specimen revealed an exophytic, dome-shaped profile with a well-circumscribed dermal nodular proliferation of banal-appearing lymphovascular spaces lined by plump CD34+ endothelial cells ( Figure 1A-C) with a dense surrounding mononuclear cell infiltrate ( Figure 1D). The majority of these small cells were CD3+ T-cells with a lesser background population of CD20+ B-cells ( Figure 1E and F). The CD4+ to CD8+ ratio was approximately 2:1 ( Figure 1G and H). A diagnosis of TRAPP was rendered. The patient was followed by his family physician, and clinical course records were not available.

Discussion
TRAPP is characterized by a solitary, polypoid, exophytic erythematous papule that most commonly arises on the head and neck [1]. TRAPP typically occurs in young adults [2], with a slight female predominance [1]. Its pathogenesis is unknown [2]. TRAPP does not have a tendency for local recurrence [2], and no recurrences after lesional excision have been reported in one study of 17 cases with a follow-up range from 24 to 120 months [1].
Histopathology shows a polypoid profile with prominent lymphovascular spaces lined by plump endothelial cells. There is a dense lymphocytic infiltrate separated from the epidermis by a grenz zone [2,4]. The infiltrate is composed of CD3+ T-cells with a mix of CD4+ and CD8+ cells [1,2]. The proportion of CD4+ to CD8+ T-cells have been inconsistently reported in the literature, with some reports suggesting CD4+ predominance [1] and others suggesting CD8+ predominance [3]. Scattered B-cells, eosinophils, and plasma cells may be seen [2]. Mild lymphocytic atypia has been reported [4].
Evolving proposals of nomenclature changes contribute to the conceptual ambiguity and diagnostic difficulty of TRAPP and similar lymphoid vascular tumors. Various terms have been proposed over the past several decades to describe this spectrum of lesions with similar morphological and immunophenotypic findings, including papular angiolymphoid hyperplasia [5], papular angiolymphoid proliferation with epithelioid features in adults and children (PALE-FACE) [6], and angiolymphoid hyperplasia with high endothelial venules (ALH-HEV) [7]. The appellation, TRAPP, was proposed just over a decade ago [1]. More recently, the term 'inflammatory lobular hemangioma (ILH)' was proposed to describe the spectrum of related cutaneous vascular lesions including TRAPP, APACHE, PALE-FACE, and ALH-HEV [8]. 'ILH' was proposed in place of 'pseudolymphoma' to emphasize the primary classification of these lesions as vascular proliferations and neoplasms, accompanied by a dense lymphocytic inflammatory infiltrate [8]. For the purposes of this discussion, the term 'TRAPP' will be used to describe the entity in question.

Pyogenic granuloma
TRAPP is most often clinically misdiagnosed as pyogenic granuloma [1]. Both PG and TRAPP have been observed in a wide range of ages, from adolescents to older adults [1,2]. While PG often presents on the head like TRAPP, its common sites also include the mucous membranes of the gingiva, lips, and nasal mucosa [9,10], which are not observed in TRAPP. PG is usually ulcerated [9], unlike TRAPP. Histologically, the lack of a well-developed lobular capillary proliferation and the presence of a brisk lymphocytic infiltrate in TRAPP draw a distinction from PG [1].

Angiolymphoid hyperplasia with eosinophilia
Like TRAPP, ALHE often presents on the head and neck regions of adults [1,9]. However, ALHE presents as grouped papules [1] rather than single lesions. In contrast to TRAPP, ALHE is characterized by plump epithelioid endothelial cells protruding into vascular lumens in a "hobnail" fashion [3,19]. TRAPP lacks this multilobular vascular pattern with a feeder vessel [1,3]. ALHE features a diffuse inflammatory infiltrate dominated by lymphoid aggregates with eosinophils [3,9,20], which is not observed in TRAPP. Additionally, TRAPP is not known to recur, while ALHE often recurs [1,2]. Fos proto-oncogene (FOS) and FosB protooncogene (FOSB) immunohistochemical expression are associated with ALHE [2,20], more frequently than TRAPP. In one report, FOSB and FOS were expressed in four and three of 11 TRAPP cases, respectively, while FOSB and FOS co-expression were observed in seven of nine ALHE cases [3].

Cutaneous epithelioid angiomatous nodule
Like TRAPP, CEAN is a cutaneous vascular proliferation that may present as a well-circumscribed solitary erythematous papule [1,2,13]. CEAN commonly occurs on the trunk and extremities [2,13], which are uncommon sites for TRAPP. While both feature a lymphocytic infiltrate, CEAN is composed of sheets of large epithelioid cells that are not observed in TRAPP [1,2,9,13].

Acral pseudolymphomatous angiokeratoma of children
TRAPP shares nearly identical histopathologic features of APACHE. The main distinguishing feature is the clinical setting. TRAPP presents as a solitary polypoid papule on non-acral sites, mainly in adults, whereas APACHE presents as multiple acral papules or plaques on the hands and feet, mainly in children [1][2][3]9], although some cases of APACHE have been reported in middle-aged and elderly adults [14]. Additionally, TRAPP features a T-cell-rich infiltrate, while APACHE features a more heterogeneous infiltrate, featuring small lymphocytes, histiocytes, plasma cells, eosinophils, and occasional giant cells [9].

Low-grade cutaneous lymphomas and lymphoproliferative disorders
On histopathology, TRAPP may raise diagnostic concerns for several lymphoproliferative disorders. Compared to PCMZLD and PCFCL, TRAPP is T-cell rich and lacks germinal centers or expanded marginal zones [1]. The predominance of T-cells in TRAPP may raise concern for cutaneous T-cell lymphomas. However, TRAPP lacks significant lymphocyte atypia and epidermotropism seen in mycosis fungoides [2,9].
Monoclonal T-cell receptor (TCR) rearrangement should not be seen in TRAPP. PCSM-TCLPD has small-to medium-sized pleomorphic CD4+/CD8-lymphocytes and PD1+ cells in clusters [18], which are not expected in TRAPP. The prominent vascular component in TRAPP is not a feature of cutaneous lymphomas or lymphoproliferative disorders.

Cutaneous lymphoid hyperplasia
Like TRAPP, CLH occurs on the upper extremities, trunk, head, and neck of adults [11] with a female predominance [1,9], but CLH does not classically appear as a polypoid papule. TRAPP lacks germinal center formation, which is often seen in CLH [9,11]. Additionally, the prominent vascular pattern [1] seen in TRAPP would be unusual for CLH.

Conclusions
TRAPP clinically presents as a solitary raised red papule or nodule on the head and neck of adults.
Histopathologically, TRAPP reveals a well-circumscribed vascular proliferation with plump endothelial cells and a dense T-cell-rich lymphocytic infiltrate. This case report and literature review highlights the clinical and histopathologic features to distinguish TRAPP from lymphomas, lymphoproliferative disorders, pseudolymphomas, and other vascular proliferations and neoplasms.

Additional Information Disclosures
Human subjects: All authors have confirmed that this study did not involve human participants or tissue.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.