Alopecia in Lymphoproliferative Disorders



Alopecia in Lymphoproliferative Disorders


Cecilia Larocca

Lynne J. Goldberg



INTRODUCTION

Alopecia is an uncommon presentation in patients with cutaneous lymphoproliferative disorders, and, when present, can provide clinicians with insight into the subtype and biology of the disease. Several types of alopecia in such patients have been reported (Table 77-1). While patients dealing with cutaneous lymphomas may have debilitating pruritus and disfiguring lesions, it is important to realize that alopecia can be equally disturbing.








TABLE 77-1 Clinical Presentations of Hair Loss in Lymphoproliferative Disorders



















Alopecia Areata–Like


Mycosis fungoides


Folliculotropic mycosis fungoides


Subcutaneous panniculitis-like T-cell lymphoma


Inflammatory Lesions (Patches, Plaques, Tumors, Nodules)


Mycosis fungoides


Erythrodermic mycosis fungoides


Sézary syndrome


Lymphomatoid papulosis


B-cell lymphoma


Follicular Papules


Hypopigmented mycosis fungoides


Folliculotropic mycosis fungoides


Syringotropic mycosis fungoides


Alopecia Universalis–Like


Erythrodermic mycosis fungoides


Sézary syndrome


Ichthyosiform mycosis fungoides


Here, we review the types of alopecia that can occur in lymphoproliferative diseases, whether primary (due to the disease process itself), or secondary, for example, due to therapeutic interventions.


ALOPECIA IN CUTANEOUS T-CELL LYMPHOMA


Mycosis Fungoides and Its Variants


Folliculotropic Mycosis Fungoides

Of all the subsets of mycosis fungoides (MF), alopecia is most commonly observed in folliculotropic MF (FMF). Multiple case series have observed alopecia in anywhere from 33% to 78% of patients with FMF.1,2,3,4 It is commonly appreciated on the scalp (Fig. 77-1); however, alopecic FMF lesions have been observed in all hair-bearing regions including the eyebrows (Fig. 77-2) and eyelashes,5 the trunk, and the upper and lower extremities including the axillae.6 Clinically, hair-bearing areas may be replaced by noninflammatory alopecia areata–like (AA-like) hair loss,7,8 grouped follicular papules, inflammatory alopecic patches or plaques, or acneiform lesions with comedones and epidermal cysts (Figs. 77-2 and 77-3). In pediatric patients, as in adults, alopecia is a prominent finding in FMF lesions; however, it can be subtle to absent in very young patients.3






FIGURE 77-1. Scalp alopecia in a 72-year-old woman with folliculotropic MF.






FIGURE 77-2. Scaly plaques, milia, and eyebrow loss in the same patient as in Figure 77-1.






FIGURE 77-3. Eyebrow loss and forehead milia in a 57-year-old woman with folliculotropic MF.

Histologically, in both inflammatory and AA-like alopecia in FMF, there is perifollicular inflammation with variable infiltration of follicular epithelium by neoplastic lymphocytes (Fig. 77-4). A majority of lesions show deposition of mucin within follicular epithelium, referred to as follicular mucinosis (FM) (Fig. 77-5).5,7 A case series of 51 patients with FMF found that 96% had evidence of FM, ranging from focal deposition to lakes of mucin, which did not correlate with the number of folliculotropic atypical lymphocytes.5 During disease progression, these patients exhibited a denser dermal infiltrate with complete effacement of hair follicles. Histologic patterns of FMF have been described by Gerami and Guitart,9 and include granulomatous inflammation, cystic and comedonal changes (Fig. 77-6), eosinophilic folliculitis, basaloid folliculolymphoid hyperplasia, pustular changes, interface dermatitis, and an interstitial dermatitis-like pattern.






FIGURE 77-4. Histopathology of a scalp follicle of the patient in Figure 77-1 reveals infiltration by lymphocytes (H&E, 1003).






FIGURE 77-5. FM on the back of the patient in Figure 77-1 (H&E, 100×).






FIGURE 77-6. Follicular infiltration and an adjacent milium from the postauricular area of the patient in Figure 77-2 (H&E, 100×).

The mechanism of alopecia may be secondary to destruction of the hair follicle from mucinous degeneration or from the dense inflammatory infiltrate.5 However, not all patients with folliculotropic infiltrates on histology develop alopecia.


Syringotropic Mycosis Fungoides

Syringotropic MF (SMF), considered by the World Health Organization–European Organization for Research and Treatment of Cancer (WHO-EORTC) to be a rare histologic subtype of FMF characterized by prominent peri-eccrine infiltration with varying degrees of eccrine hyperplasia and folliculotropism (Figs. 77-7 and 77-8), can also present with alopecia (Figs. 77-9 and 78-10).10 Clinically, lesions of SMF are more commonly found on the trunk and extremities, unlike the predominant head and neck distribution of FMF. Lesions of SMF may present as inflammatory scaly patches and plaques with prominent alopecia,11 as well as alopecic hypopigmented patches composed of follicular erythematous papules.12 Histologically, there is significant overlap between SMF and FMF. The largest case series of SMF reviewed a total of 19 patients and found that 63% had clinical alopecia, and 68% exhibited folliculotropism histologically.13






FIGURE 77-7. Histopathology of SMF on the shoulder of the patient in Figure 77-9. Low power showing epidermotropism and a syringotropic infiltrate near the deep specimen margin (H&E, 40×).






FIGURE 77-8. Histopathology of SMF. Higher power showing a nodular lymphoid infiltrate surrounding hyperplastic eccrine glands (H&E, 200×).






FIGURE 77-9. Scalp alopecia in a 74-year-old patient with SMF.






FIGURE 77-10. Beard alopecia and comedones in the same patient with SMF.

The histologic findings in SMF were originally thought to represent a benign inflammatory dermatosis called “syringolymphoid hyperplasia” or “syringolymphoid hyperplasia with alopecia.”12 It is now appreciated that these early cases in the literature are syringotropic variants of MF. However, there are isolated case reports of syringolymphoid hyperplasia presenting with similar alopecic patches that are felt to have no histologic evidence of cutaneous lymphoma.14,15 The authors in these cases have proposed that this entity is a syringotropic variant of FM.15


Patch, Plaque, and Tumor Stage Mycosis Fungoides

Two patterns of alopecia have been described in patients with MF. Alopecia may be limited to clinically overt patches, plaques, or tumors (Fig. 77-11) or may appear as AA-like patches of hair loss in areas clinically devoid of inflammatory skin changes.7






FIGURE 77-11. Alopecia on the scalp due to tumor stage MF in a 57-year-old man.

The incidence of alopecia in patch or plaque lesions of MF is unknown. A large retrospective review of 1,550 patients by Bi et al.,7 including patients with MF, folliculotropic MF, and Sézary syndrome (SS), identified only six patients with alopecia in patches or plaques in the absence of histologic evidence of folliculotropism. However, the total number of Stage IA-IIB MF patients in this series is unknown. When MF evolves from patches and plaques to tumors, there is often a loss of epidermotropism and a denser dermal infiltrate with complete effacement of hair follicles.5,10 Thus, it is reasonable to conclude that alopecia in tumor stage MF is a result of follicular destruction by the lymphocytic infiltrate (Fig. 77-12). The histologic findings in alopecic patch and plaque stage MF are not sufficiently characterized to address the mechanism of alopecia in these early stages.






FIGURE 77-12. Histopathology of follicular involvement in the tumor of the patient in Figure 77-11. Low power showing a dense lymphoid infiltrate, distorted follicular architecture, and intrafollicular lymphocytes (H&E, 100×).

Bi et al.7 identified seven Stage IA-IIA MF patients with AA-like hair loss, the majority of whom had disease that was limited to the scalp. The remaining patients had AA-like patches on the face and/or extremities. In all patients, alopecia developed at the same time, or after, the development of MF lesions elsewhere on the body. Histologic evaluation of AA-like lesions in MF patients has found epidermotropic infiltrates of predominately CD4+ T lymphocytes, except in one child with a predominance of CD8+ T cells. A clonal T-cell receptor gene rearrangement was found in two of five biopsies.

Very rarely, patients without known malignancy develop alopecia as a presenting complaint. This condition has been termed “scalp alopecia due to a clinically unapparent or minimally apparent neoplasm,” or SACUMAN.16 Although this is most commonly the result of metastatic breast cancer,16 one case report identified MF as the cause of alopecia prior to the observation of MF lesions elsewhere.17


Erythrodermic Cutaneous T-Cell Lymphoma

Erythrodermic cutaneous T-cell lymphoma consists of three subtypes: SS, erythrodermic MF, and erythrodermic cutaneous T-cell lymphoma, not otherwise defined.18 Despite their similar histology, alopecia appears to be more common in SS (Fig. 77-13). Small case series have indicated that between 16.5% and 21% of SS patients have alopecia.19,20 Erythrodermic MF, in the presence or absence of SS, can exhibit patchy alopecia21,22 or diffuse hair loss with an alopecia universalis–like presentation.23 Miteva et al.23 described dermatoscopic findings in patients with this pattern of hair loss, which included perifollicular or diffuse scaling, a reduction in follicular orifices, and follicular openings with short, broken hairs or keratotic horny spines. Histologically, these patients had decreased follicular density, absent sebaceous glands, an interface-like epidermotropic lymphoid infiltrate of the follicular epithelium with focal giant cells and FM. Hair follicles were predominately in telogen phase and miniaturized. Several follicular infundibulae showed lamellar hyperkeratosis surrounding vellus hairs. The alopecia in these patients may be directly related to the presence of an atypical lymphocytic infiltrate, secondary to FM, or indirectly related, as erythroderma in the absence of cutaneous lymphoma (e.g., from pityriasis rubra pilaris) can lead to patchy or diffuse but reversible alopecia.24,25 In these cases, alopecia may be caused by the effect of the inflammatory cytokine milieu on cycling hair follicles, which triggers anagen hair loss with dystrophic hairs in the acute stage and follicular miniaturization in the chronic stages.23






FIGURE 77-13. Scalp and eyebrow loss in a 70-year-old man with SS.


Hypopigmented Mycosis Fungoides

Hypopigmented MF is a clinical variant of MF that is most commonly present in the pediatric population.26 Interestingly, alopecia has been observed in a subset of these patients. Clinically, this presents as follicular papules within alopecic lesions of hypopigmented MF (Fig. 77-14). Folliculotropism is seen histologically (Fig. 77-15).3






FIGURE 77-14. Hair loss on the leg in a 7-year-old girl with hypopigmented MF.






FIGURE 77-15. Histopathology of the patient in Figure 77-14. Careful inspection revealed focal FM (H&E, 100×).


Ichthyosiform Mycosis Fungoides

Very rarely, patients may present with a diffuse or localized ichthyosiform eruption overlying MF lesions. This uncommon secondary change, reported in less than 20 patients, predominately occurs in FMF,27,28,29 but has also been reported to occur in patients with patch and plaque MF,30,31,32,33 granulomatous MF,34 lymphomatoid papulosis (LyP),35 and anaplastic large-cell lymphoma (ALCL).36,37 Four patients have been reported to have alopecia develop in ichthyosiform MF. Three patients with a diffuse ichthyosiform eruption in the setting of FMF presented with a moth-eaten pattern of patchy alopecia of the scalp and sparse body hair.28,29,38 In these patients, skin biopsies revealed focal parakeratosis, hyperkeratosis, acanthosis, and a thinned granular layer consistent with ichthyosis, with an underlying atypical lymphocytic infiltrate. The lymphocytic infiltrate displayed folliculotropism in a pattern consistent with FMF. A fourth patient with ichthyosis and granulomatous MF presented with alopecia universalis. Interestingly, his skin biopsy had evidence of folliculotropism along with granulomatous inflammation.34 It is unclear if this represents FMF with granulomatous change.

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Nov 8, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Alopecia in Lymphoproliferative Disorders
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