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Background
Alopecia mucinosa (follicular mucinosis) occurs in the 3rd to 4th decades. There are various presentations.
Benign transient form Plaques or grouped follicular papules limited to the face or scalp with alopecia Disseminated form Plaques and nodules on the extremities, face, and trunk
Usually lasts>2 yrsDisseminated form associated with lymphoma Widespread lesions associated with malignant lymphoma or mycosis fungoides
15-30% of casesIn the patients with progression to lymphoma, a monoclonal T cell population has been identified in all cases and in over 50% of cases associated with the primary disease. Long term follow-up of 27 months did not reveal progression to lymphoma but obviously long term surveillance is needed.
The pathologist finds a perifollicular, follicular, and perivascular lymphocytic infiltrate. The hair follicle and sebaceous glands show mucin which may coalesce to form small cysts. In cases associated with lymphoma, the inflammatory infiltrate is deeper and more intense. In addition, there is atypicality of the lymphocytes as well as Pautrier microabscesses.
There are secondary causes of follicular mucinosis.
Lichen simplex chronicus
Hypertrophic lichen planus
Discoid lupus erythematosus
Acne vulgaris
Pseudolymphoma
Melanocytic nevi
Arthropod bite
Atopic dermatitis
Grover's disease
Actinic prurigo
Infundibulofolliculitis
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Follicular mucinosis INCIDENCE Rare but secondary forms more common
DISEASE ASSOCIATIONS CHARACTERIZATION ACUTE MYELOBLASTIC LEUKEMIA Follicular mucinosis as a presenting sign of acute myeloblastic leukemia.
Sumner WT, Grichnik JM, Shea CR, Moore JO, Miller WS, Burton CS.
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Am Acad Dermatol 1998 May;38(5 Pt 2):803-5 Abstract quote
Follicular mucinosis is often associated with mycosis fungoides and has been rarely observed to occur with other neoplastic and inflammatory conditions.
We describe a 60-year-old patient with follicular mucinosis who later developed acute myelogenous leukemia.
This is the first reported case of follicular mucinosis as a presenting sign of acute myeloblastic leukemia in the absence of mycosis fungoides or leukemia cutis.
EOSINOPHILIC FOLLICULITIS HIV-Associated eosinophilic folliculitis and follicular mucinosis.
Buezo GF, Fraga J, Abajo P, Rios L, Dauden E, Garcia-Diez A.
Department of Dermatology, Hospital Universitario de la Princesa, Universidad Autonoma, Madrid, Spain.
Dermatology 1998;197(2):178-80 Abstract quote
The term HIV-associated eosinophilic folliculitis (EF) designates an idiopathic dermatitis that appears in HIV-infected patients with different clinical manifestations but with a distinctive histological feature characterized by a predominantly eosinophilic infiltrate in the follicular infundibula. On the other side, follicular mucinosis (FM) is a reaction pattern in the follicular epithelium, characterized by a mucinous degeneration of the outer sheath of follicles and sebaceous glands. It has been described in association with a variety of unrelated conditions.
We report 2 HIV-infected patients with a pruritic papular eruption. Histopathological study revealed the coexistence of EF and FM.
To our knowledge, this is the first report that describes this association. The possible relationship between these two entities is discussed.
MELANOCYTIC NEVUS Follicular mucinosis in association with a melanocytic nevus. A report of two cases.
Jordaan HF.
J Cutan Pathol 1987 Apr;14(2):122-6 Abstract quote
A report of two cases. Jordaan HF. The recognition of follicular mucinosis as a distinct entity is accorded to Pinkus in a 1957 paper under the title Alopecia mucinosa. A primary and a secondary form is recognised. Recently secondary follicular mucinosis was observed in our laboratory in association with an intradermal and a compound melanocytic nevus.
To my knowledge this association has not been reported previously.
MYCOSIS FUNGOIDES
A case of follicular mycosis fungoides with follicular mucinosis: a rare association.Campanati A, Giangiacomi M, Goteri G, Penna L, Turtu S, Offidani AM.
Am J Dermatopathol 2002 Oct;24(5):423-6 Abstract quote Follicular mycosis fungoides (FMF) is a rare cutaneous T cell lymphoma characterized by an atypical lymphoid infiltrate spreading within and around hair follicles without epidermotropism or follicular mucin deposits. Its occasional presentation with minimal epidermal involvement and/or follicular mucinosis suggests the need for uniform histologic criteria.
We describe a new case of FMF associated with follicular mucinosis and discuss its morphologic spectrum of presentation.
OFUJI PAPULOERYTHRODERMA Ofuji papuloerythroderma associated with follicular mucinosis in mycosis fungoides.
Suh KS, Kim HC, Chae YS, Kim ST.
Department of Dermatology, Kosin Medical College, Pusan, South Korea.
J Dermatol 1998 Mar;25(3):185-9 Abstract quote
Ofuji papuloerythroderma is a distinctive clinical entity of unknown etiology, which may occasionally be associated with B cell and T cell lymphoma or visceral malignancy.
We report a case of papuloerythroderma associated with follicular mucinosis in mycosis fungoides (MF) that raises the possibility of papuloerythroderma as a form of prelymphomatous skin eruption.
This specific papuloerythroderma responded well to the Re-PUVA treatment, which is a combination of etretinate and PUVA photochemotherapy.
PATHOGENESIS CHARACTERIZATION CLONAL REARRANGEMENT Clonal rearrangement of the T cell receptor beta gene in the circulating lymphocytes of erythrodermic follicular mucinosis.
LeBoit PE, Abel EA, Cleary ML, Hoppe RT, Williams ML, Wood GS, Parslow TG.
Department of Pathology, School of Medicine, University of California, San Francisco 94143.
Blood 1988 May;71(5):1329-33 Abstract quote
Follicular mucinosis is a condition characterized by the abnormal accumulation of acidic mucopolysaccharides in hair follicles. It is classically described as occurring idiopathically in young persons and within the infiltrates of mycosis fungoides in older individuals.
We report a 12-year-old girl who had erythrodermic follicular mucinosis, hypereosinophilia, circulating Sezary cells, and both immunophenotypic and genotypic evidence of T cell neoplasia.
Erythrodermic follicular mucinosis may represent an unusual variant of the Sezary syndrome, which to date has not been described in children or adolescents.
Primary follicular mucinosis: Long-term follow-up of patients younger than 40 years with and without clonal T-cell receptor gene rearrangement.Brown HA, Gibson LE, Pujol RM, Lust JA, Pittelkow MR.
Department of Dermatology and Section of Dermatopathology and Department of Medicine and Division of Hematology, Mayo Clinic, Rochester; and Hospital de la Santa Creu i Sant Pau, Barcelona.
J Am Acad Dermatol 2002 Dec;47(6):856-62 Abstract quote Since the original descriptions of follicular mucinosis, accumulating experience shows that patient age, distribution of lesions, and duration or extent of disease do not reliably distinguish benign primary follicular mucinosis from secondary follicular mucinosis, associated with cutaneous lymphoma. More recently, it has been suggested that individuals with follicular mucinosis demonstrating a clonal T-cell receptor gene rearrangement may be at higher risk for the development of lymphoma.
Long-term follow-up of 7 patients younger than 40 years with primary follicular mucinosis are reported. In all cases, there was no clinical or histologic evidence of associated dermatoses or lymphoma at the time of diagnosis. Five of the patients have clonal T-cell gene rearrangement as determined by Southern blot analysis.
Clinically, at the time of diagnosis, lesions of primary follicular mucinosis ranged from papules confined to the face to widespread cutaneous plaques. After a mean follow-up of 10 years (range, 5-23 years) from the onset of disease, the majority of patients continue to have cutaneous manifestations of follicular mucinosis despite various treatments. There is no evidence of progression to cutaneous T-cell lymphoma in any patient despite the presence of a clonal T-cell receptor gene rearrangement.
Continued prolonged follow-up of patients with clonal primary follicular mucinosis is necessary to determine the significance of infiltrates harboring a T-cell receptor gene rearrangement. However, in our experience with this group of selected patients, primary follicular mucinosis has been a clonal disorder with limited or "benign" cutaneous manifestations.
HYALURONATE EXPRESSION
- CD44 and hyaluronate expression in follicular mucinosis.
Kaya G, Augsburger E, Chavaz P, Saurat JH.
Department of Dermatology, DHURDV, University Hospital of Geneva, Geneva, Switzerland.
J Cutan Pathol. 2006 Mar;33(3):227-30. Abstract quote
BACKGROUND: CD44 is a membrane glycoprotein and the major cell-surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans.
METHODS: We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44-specific antibodies and biotinylated HA-binding protein (HABP), respectively.
RESULTS: No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin-accumulated areas compared to the interfollicular keratinocytes.
CONCLUSION: Our results suggest an active secretion of HA by follicular cells in follicular mucinosis.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION VARIANTS CHILDHOOD Mycosis fungoides with mucinosis follicularis in childhood.
Hess Schmid M, Dummer R, Kempf W, Hilty N, Burg G.
Department of Dermatology, University of Zurich, Switzerland.
Dermatology 1999;198(3):284-7 Abstract quote
Mycosis fungoides is a cutaneous T-cell lymphoma (CTCL) usually observed in mid to late adulthood. It occurs only rarely during childhood. Follicular mucinosis is a chronic dermatosis involving the sebaceous glands and outer root sheaths. It is normally differentiated into a juvenile benign form and an adult form possibly associated with mycosis fungoides.
We report a 12-year-old boy who presented with an 8-month history of erythematous mucinous plaques on the scalp. Three months later, he developed erythematous patches and plaques on his whole body, accompanied by cervical lymphadenopathy. A biopsy showed follicular mucinosis and epidermotropism of the lymphocytic infiltrate. Immunophenotyping and a PCR clonality test were consistent with CTCL. The patient received PUVA treatment and local steroids, resulting in partial remission.
Mycosis fungoides should be considered in the differential diagnosis of chronic, scaling dermatoses in childhood. Moreover, follicular mucinosis in childhood can be associated with mycosis fungoides.
MYCOSIS FUNGOIDES Rapidly progressing mycosis fungoides presenting as follicular mucinosis.
Bonta MD, Tannous ZS, Demierre MF, Gonzalez E, Harris NL, Duncan LM.
Dermatopathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Am Acad Dermatol 2000 Oct;43(4):635-40 Abstract quote
Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides.
We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides.
In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Alopecia mucinosa is mycosis fungoides.
Boer A, Guo Y, Ackerman AB.
Department of Dermatology, Klinikum der J W Goethe Universitat, Frankfurt, Germany.
Am J Dermatopathol. 2004 Feb;26(1):33-52. Abstract quote
Confusion abounds regarding the terms "follicular mucinosis" and "alopecia mucinosa," not only concerning definition and essential character, but of relationships between themselves on one hand and between themselves and mycosis fungoides on the other.
We address here those issues in methodical fashion, first in historical perspective by review, scrupulously and critically, of what has been said in the many articles devoted to the subject; we next tell how the terms "alopecia mucinosa" and "follicular mucinosis" came to be and how they are employed currently; we then set forth our own observations pertinent to clinical, histopathologic, and biologic aspects of the condition called, conventionally, "alopecia mucinosa," those observations based on our own findings in sections of tissue cut from 54 biopsy specimens taken from 45 patients, all of them having been signed out previously as "follicular mucinosis;" we proceed to forge clinico-pathologic correlation of lesions in 14 of those 45 patients, utilizing assessments, by examination grossly and microscopically, of attributes in the very same lesion.
Last, we propose a concept, and a terminology that derives from it, that synthesizes all that is known now about "alopecia mucinosa" and "follicular mucinosis," in particular the relationship of "alopecia mucinosa" to mycosis fungoides, including "follicular," "syringotropic," and erythrodermic manifestations of it. In short, we affirm that so-called alopecia mucinosa is but one of many morphologic manifestations of mycosis fungoides.Benign idiopathic versus mycosis fungoides-associated follicular mucinosis.
Nickoloff BJ, Wood C.
Pediatr Dermatol 1985 Mar;2(3):201-6 Abstract quote
A study was undertaken in an attempt to identify useful histologic criteria that may allow differentiation between benign idiopathic and mycosis-fungoides-associated follicular mucinosis.
We chose young patients because no person under 20 years of age with coexisting follicular mucinosis and mycosis fungoides disease has ever been reported.
Our three most important observations in benign juvenile idiopathic follicular mucinosis were as follows: The lymphocytic infiltrate was generally confined to follicular, perifollicular, or perivascular zones with no extension of either normal or atypical mononuclear cells into the epidermis or into papillary/reticular dermis. Within follicular epithelium there were dense collections of lymphocytes with occasionally atypical-appearing nuclei in three of the eight patients, but never as Pautrier microabscesses. There was absence of a significant associated plasma cell or eosinophil-containing inflammatory dermal infiltrate.
These findings are in contrast to those of older patients with follicular mucinosis and mycosis fungoides.
VARIANTS FOLLICULOTROPIC Folliculotropic T-cell lymphocytosis (mucin-poor follicular mucinosis).
Kossard S, Rubel D.
Skin and Cancer Foundation Australia, New South Wales, Australia.
Australas J Dermatol 2000 May;41(2):120-3 Abstract quote
A 48-year-old man presented with multiple asymptomatic patches of hair loss over his trunk and limbs associated with focal keratotic follicular plugs.
Multiple skin biopsies showed a panfollicular lymphocytic infiltrate associated with follicular hyperkeratinization, minimal follicular spongiosis, focal basaloid follicular hyperplasia but no overt follicular mucinosis. The lymphocytes were small and there was no atypia. Immunoperoxidase stains showed that the follicular lymphocytes were T cells and predominantly CD4 positive with HLADr (LN3) expressed on their surface. There were insufficient clinical or histopathological features to make a diagnosis of folliculotropic T-cell lymphoma. This case currently may be classified best as folliculotropic T-cell lymphocytosis and may represent a mucin-poor counterpart of follicular mucinosis. Such cases may pursue an indolent course or may evolve to folliculotropic T-cell lymphoma, mycosis fungoides or anaplastic lymphoma.
The term folliculotropic T-cell lymphocytosis may be useful for similar cases lacking clinical or histological criteria for lymphoma and lacking follicular mucinosis.
SYRINGOLYMPHOID HYPERPLASIA Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma.
Tannous Z, Baldassano MF, Li VW, Kvedar J, Duncan LM.
Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon.
J Am Acad Dermatol 1999 Aug;41(2 Pt 2):303-8 Abstract quote
Syringolymphoid hyperplasia with alopecia is an uncommon chronic dermatosis of which 9 cases have been reported, with or without follicular mucinosis or cutaneous T-cell lymphoma.
We report a patient with cutaneous T-cell lymphoma and syringolymphoid hyperplasia and follicular mucinosis and review the previously reported cases. All reported cases with syringolymphoid hyperplasia were men (10 of 10), with the clinical findings of alopecia (9 of 10) and anhidrosis (3 of 10). Only 3 of 10 cases had associated follicular mucinosis. Of the 7 cases investigated, 6 were found to hve cutaneous T-cell lymphoma. Three patients were not investigated for cutaneous T-cell lymphoma. Although syringolymphoid hyperplasia can be idiopathic, it can also reflect a syringotropic cutaneous T-cell lymphoma.
Careful follow-up with a biopsy of persistent lesions is recommended to evaluate for the presence of lymphoma.
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE Follicular mucinosis: a detailed morphologic and immunopathologic study.
Lancer HA, Bronstein BR, Nakagawa H, Bhan AK, Mihm MC Jr.
J Am Acad Dermatol 1984 May;10(5 Pt 1):760-8 Abstract quote
Two patients with the benign type of follicular mucinosis (FM) are presented. Their clinical features and course were characteristic for this subgroup of FM.
Light and electron microscopy, direct immunofluorescence, and immunoperoxidase cell marker studies were undertaken to characterize the nature of the disease process. Light microscopy confirmed the follicular outer root sheath and sebaceous gland epithelial degenerative changes. The infiltrating inflammatory cells were morphologically benign. Electron microscopy detailed the cellular associations in the areas of degenerative change. Disattached keratinocytes were closely apposed to significant numbers of macrophages and Langerhans cells. Direct immunofluorescence studies demonstrated primarily complement (C3) and fibrinogen/fibrin in areas of reticular degeneration. Immunoperoxidase studies revealed large numbers of T cells and macrophages and a striking increase in the number of Langerhans cells in the affected follicular epithelium.
The findings suggest that cell-mediated immune mechanisms may play a role in the pathogenesis of this disorder.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Dermal mucinosis MYCOSIS FUNGOIDES
Follicular mucinosis: a clinicopathologic, histochemical, immunohistochemical and molecular study comparing the primary benign form and the mycosis fungoides- associated follicular mucinosis.|
Rongioletti F, De Lucchi S, Meyes D, Mora M, Rebora A, Zupo S, Cerruti G, Patterson JW.Section of Dermatology, DISEM, University of Genoa, Genoa, Italy.
J Cutan Pathol. 2009 Jul 14. Abstract quote
Objectives: To determine (i) whether primary (idiopathic) follicular mucinosis (PFM) and lymphoma-associated follicular mucinosis (LAFM) are distinct or related entities and whether there are reliable criteria that allow the two forms to be distinguished, (ii) the histochemical properties and consequently the type of mucin that accumulates in the follicle in PFM and LAFM, and (iii) whether there is any difference between the staining properties of mucin in patients with PFM and LAFM.
Methods: Thirty-one patients were divided into two groups. Group 1 comprised 20 patients with no associated mycosis fungoides or Sézary syndrome (PFM) and group 2 was made up of the other 11 patients who had clinicopathological evidence of cutaneous T-cell lymphoma (LAFM). The biopsy specimens of the patients were studied with histopathological, histochemical and immunohistochemical methods. Molecular biology studies were also performed.Results: Patients with PFM were more frequently younger (mean age 39 years), women (F:M=3:1), and presented with a solitary lesion involving the head/neck area more often than patients with LAFM who were older (mean age 54 years), men (M:F=2:1), and presented with multiple lesions on areas of the body other than the head/neck area. As for histopathological findings, large cystic spaces filled with mucin and a slight perivascular and periadnexal polyclonal infiltrate of mostly non-atypical lymphocytes without epidermotropism and with an equivalent CD4+/CD8+ cell rate were more suggestive of PFM. On the contrary, patients with LAFM were more probably to present with a dense band-like infiltrate with some atypical lymphocytes and sign of epidermotropism, a prominent CD4+ immunophenotype and a monoclonal rearrangement of the infiltrate. Mucin proved to be a dermal-type mucin, composed of both hyaluronic acid and sulfated glycosaminoglycans. No differences were found in the composition of the follicular mucin in the PFM compared with LAFM.
Conclusions: Although no single, indisputable feature can reliably differentiate PFM from LAFM and a considerable overlapping among the two groups exists, the use of multiple clinical, histological and immunopathological criteria associated with gene rearrangement analysis can be useful in evaluation of those patients.OFUJI'S DISEASE
Ofuji's disease with follicular mucinosis and its differential diagnosis from alopecia mucinosa.Lee JY, Tsai YM, Sheu HM.
Department of Dermatology, National Cheng Kung University, Tainan, Taiwan.
J Cutan Pathol. 2003 May;30(5):307-13. Abstract quote OBJECTIVES: Ofuji's disease (OD) or eosinophilic pustular folliculitis and human immunodeficiency virus-associated eosinophilic folliculitis (HIV-EF) both show eosinophil-rich folliculocentric infiltrates, and it is not clear whether they are distinguishable pathologically. Follicular mucinosis (FM) has been observed in lesions of EF; such cases need to be differentiated from alopecia mucinosa (AM).
METHODS: We compared various pathologic features in 13 cases of OD, 10 cases of non-OD-typed papular EF (seven HIV-positive and three HIV-negative), and five cases of AM.
RESULTS: All cases of EF showed eosinophilic infiltrates affecting mainly the isthmus or/and sebaceous gland. Eosinophil-rich pilosebaceous pustules or/and microabscesses were noted in 69% of the biopsy specimens of OD, 73% of papular EF, 71% of HIV-EF, and 0% of AM. Mucin deposits, often abundant, were found in sebaceous lobules or/and isthmus in 41% of OD and 100% of AM. Compared with AM, OD with FM tended to show more numerous eosinophils, less abundant mucin, and most significantly, eosinophilic infundibular pustule or sebaceous microabscess.
CONCLUSION: Our study suggests that OD and HIV-EF are indistinguishable pathologically and the diagnosis requires clinical correlation. FM was not uncommonly seen in lesions of OD. OD with FM may be difficult to differentiate from FM, especially in cases presenting with non-annular or non-pustular lesions, but the diagnosis might be facilitated by finding eosinophil-rich pustule, microabscess, or infiltrate in pilosebaceous units microscopically.
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