Poikiloderma vasculare atrophicans: a distinct clinical entity?

This paper describes a typical case of poikiloderma vasculare atrophicans (PVA) in a 48-year-old female. Histologically, the features were suggestive of PVA with the absence of Pautrier's microabscess or atypical lymphoid cells. The biopsy specimen was positive for cluster of differentiation (CD) 8 on immunohistochemical staining. Its exact pathogenesis remains obscure, and it remains unclear whether PVA actually is mycosis fungoides (MF), a forme fruste of MF, or a distinct and benign dermatosis with CD8+ phenotype that can perhaps be labeled as PVA. However, it has a long benign clinical course without progression to tumor stage of MF in most cases, and its status within the spectrum of cutaneous T-cell lymphoma remains poorly understood. Yet it is imperative to distinguish PVA from poikilodermic MF.

What was known?

Poikiloderma is usually a manifestation of (1) genodermatoses such as Kindler syndrome, Rothmund–Thomson syndrome, dyskeratosis congenita, xeroderma pigmentosum, Bloom syndrome, Cockayne syndrome, and so on; (2) collagen vascular disorders like dermatomyositis or systemic sclerosis; or (3) poikilodermic mycosis fungoides.

Introduction

Poikiloderma is characterized generally by erythema, atrophy, telangiectasias, hypo, and hyperpigmentation in a reticulate pattern. It is usually considered a manifestation of varied dermatoses and seen commonly in association with (1) genodermatoses such as Kindler syndrome, Rothmund-Thomson syndrome, dyskeratosis congenita, xeroderma pigmentosa, Bloom syndrome, Cockayne syndrome, and so on; (2) collagen vascular disorders like dermatomyositis or systemic sclerosis; or (3) as an early stage of mycosis fungoides (MF) or poikilodermic MF. Poikiloderma vasculare atrophicans (PVA; synonyms: Parakeratosis variegata, parapsoriasis lichenoides, lichen variegates, parapsoriasis poikilodermique) usually manifests clinically as asymptomatic or sometimes mildly itchy, red–brown papules with mild scaling, coalescing into net-like patterned lesions. It mostly affects middle-aged individuals with some male preponderance. The sites of predilection are the breast, abdomen, and buttocks, or flexures. Its status within the spectrum of cutaneous T-cell lymphoma is poorly understood. We describe a typical case of PVA having a prolonged clinical course without actual progression to MF, suggesting its benign nature.

Case Report

This 48-year-old female presented with asymptomatic, generalized brownish-red papulo-macules in a network-like pattern interspersed with atrophy and prominent telangiectasias predominantly over the breasts, abdomen, back, and extremities [Figure 1]. Upper limbs, especially extensors, and front of the trunk were involved more severely than the lower limbs and back. The lesions had begun over the thighs and progressed to involve the entire body in a period of 10 years. Her face, palms, and soles were not involved. Hair, nails, and mucous membranes were normal. She was obese, had no lymphadenopathy, and systemic examination was normal. Laboratory investigations including complete hemogram, serum biochemistry, antinuclear antibody (ANA), urinalysis, and X-rays/computed tomography scans of chest, abdomen, and pelvic organs showed no abnormality. Histologic features of effaced rete ridges, hydropic degeneration of basal cells, focal dense band-like infiltrate of lymphoid cells (prominently perivascular), dilated capillaries and extravasation of red blood cells, melanin incontinence and a few melanophages in the upper dermis, and no Pautrier's microabscess or atypical lymphoid cells were suggestive of PVA [Figure 2]. Immunohistochemical staining was negative for cluster of differentiation (CD) 3, CD4, and CD7 and positive for CD8. Molecular/polymerase chain reaction (PCR) studies were not done because of economic reasons. She was treated with PUVA-SOL (oral methoxsalen 20 mg followed by sunlight exposure) on alternate days. She did not continue treatment after 3 months and discontinued follow-up after another 2 years despite counseling for the need of repeat future biopsies. The status of her skin lesions during follow-up had remained unchanged both clinically and histologically.

Figure 1

Poikiloderma vasculare atrophicans–erythematous and brownish-red papulo-macules in a network-like pattern interspersed with atrophy and prominent telangiectasias predominantly over the abdomen and breasts. Similar lesions were present over the back and extremities

Figure 2

Orthokeratosis, moderate-to-marked epidermal thinning, effacement of the rete ridges, and focal band-like dense cellular infiltrate of lymphoid cells in upper dermis (a). Hydropic degeneration of basal cells, melanin incontinence, dermal edema with focal exocytosis (arrow), and a few melanophages in the upper dermis (b). Arrows indicate prominent perivascular infiltrate, dilated capillaries, and extravasation of red blood cells within the upper dermis (c) [stain: hematoxylin and eosin (H and E), ×40]. A positive immunohistochemical staining of cells with CD8 surface markers in the upper dermis (d)

Discussion

Several clinicopathologic forms of PVA (hypopigmented, vesiculobullous, erythrodermic, pustular) have been described.[1] However, its pathogenesis and status within the spectrum of cutaneous T-cell lymphoma remains poorly elucidated. Some workers consider PVA as a rare variant of early-stage MF as its histologic features are similar to those of long-standing patch or plaque stage of classic MF with poikiloderma.[23] Another view is that PVA is per se a premycosis, an early-stage MF or “poikilodermic MF” presenting clinically with hypopigmentation and hyperpigmentation in reticulate pattern, dryness, atrophy, and telangiectasias.[3] In view of its prolonged benign clinical course without progression to tumor stage after several years, even ≥30 years in some cases, it also remains debatable whether this is a distinct benign dermatosis.[45] However, MF (particularly its poikilodermic variant), being the commonest of cutaneous T-cell lymphomas, remains the most crucial differential of the more benign PVA. Repeated biopsies and clinicopathologic correlation, of course, is of crucial value in the early diagnosis of MF. However, immunohistologic features of MF are not distinct and may be observed in other inflammatory dermatoses as well.[6] Staining for CD3 or CD4 highlights epidermotropic T cells, but staining for CD7 has a limited usefulness in early-stage MF as partial loss of CD7 in T cells is usual in other inflammatory dermatoses. On the other hand, CD8 + phenotype of MF is reportedly observed having a long, mild, indolent, and benign clinical course.[4] The recent PCR techniques with enhanced sensitivity have limitations of low specificity as they may detect a population of monoclonal T lymphocytes present in other benign inflammatory dermatoses as well.[6] Hence, the absence of clonality or negative immunohistochemical results is not construed to exclude the diagnosis of MF. Similarly, monoclonal rearrangement of the T-cell receptor (TCR) gene or immunohistochemical analysis of TCRs are not considered useful in differentiating MF from other chronic benign inflammatory dermatoses (psoriasis, chronic contact dermatitis, lichen planus, lichen sclerosis, etc.) as monoclonal rearrangement in MF is seen in only 50%-60% cases.[789] Hence, the presence or absence of monoclonal pattern of TCR gene rearrangement is not an absolute criterion to diagnose MF in early stage. Moreover, all these sophisticated techniques are too complex, expensive, and have limited availability in routine clinical settings. Our patient had characteristic clinicopathologic presentation of PVA with an observed long benign clinical course without progression to tumor stage of MF. However, it remains unclear whether PVA actually is MF, a forme fruste of MF, a CD8+ MF phenotype, or a distinct and benign entity that can perhaps be labeled as PVA. The last one appears more meaningful to us as distinguishing benign cases of PVA from pokilodermic MF will save these patients from unnecessary psychological distress and expensive therapy for MF. However, regular long-term clinicopathologic and immunohistochemical follow-up studies of these patients will perhaps clear some of these unresolved issues.

What is new?

Poikiloderma vasculare atrophicans (PVA) with a characteristic histopathology, cluster of differentiation (CD) 8 + cell infiltrate on immunohistochemical staining, and long benign clinical course can perhaps be labeled as a distinct and benign PVA phenotype.