Follicular mycosis fungoides: Clinicohistopathologic features and outcomes in a series of 12 Chinese cases.

Background Follicular mycosis fungoides is a distinct variant of mycosis fungoides with a broad clinical spectrum. Recently, many studies have indicated that follicular mycosis fungoides should be divided into different subtypes with disparate prognoses. Objective To define the clinicohistopathologic features and outcomes of follicular mycosis fungoides and to identify risk factors that may be related to the prognosis of Chinese patients with follicular mycosis fungoides. Materials and methods We conducted a single-centre retrospective study and reviewed the clinical, histopathologic and immunophenotypic data of 12 patients diagnosed with follicular mycosis fungoides between 2009 and 2020 in the Department of Dermatology of West China Hospital of Sichuan university. Results A total of 12 patients (seven males and five females) with a mean age of 30 ± 14 years (age range 16-55 years) were included. Scalp and face were the most common involved sites (100%). Follicular papules, acneiform lesions, plaques, and nodules, were the main clinical presentations. Histopathological findings were consistent with the classic manifestations of follicular mycosis fungoides, including folliculotropism, perifollicular and intrafollicular lymphocytic infiltrates and mucinous degeneration. Interferon α-1b was the most common treatment. Four patients died of follicular mycosis fungoides in three years. Notably, immunohistochemical analysis revealed a decreased number of CD20+ cells in the deceased patients. Limitations This is a retrospective evaluation with a small number of cases; further prospective studies are warranted to support our inferences. Conclusion Our patients were much younger than in previous studies. The observed difference in this cohort may be explained by race, in addition to the limited number of cases. A decreased number of B cells might be associated with a poor prognosis, and more studies are necessary to discover the role of B cells in follicular mycosis fungoides as well as in mycosis fungoides.

Hypopigmented mycosis fungoides mimicking leprosy successfully treated with oral and topical corticosteroids: a new great imitator?

Hypopigmented mycosis fungoides (HMF) is a rare variant of patch stage MF, which is often misdiagnosed. A 35-year-old male presented with non-pruritic white patches on his chest that had been present for 10 years. The patient had previously been treated for leprosy without any improvement. Physical examination showed well-defined multiple hypopigmented patches and macules on the chest, posterior trunk, and gluteus, with some lesions exhibiting anhidrosis and central erythema. The result of sensibility examination was unclear. Slit-skin-smear examination for acid-fast bacilli and anti-phenolic-glycolipid-1 examination were negative. Histopathological examination showed Pautrier microabscesses. The patient was diagnosed with HMF and was treated with 16 mg methylprednisolone b.i.d., topical application of desoximetasone, and 1% methoxsalen lotion followed by sun exposure. A significant improvement was observed during the following 6 months. This case shows that HMF needs to be considered in patients presenting with chronic unexplained hypopigmented patches to avoid unnecessary treatment and progression to more advanced stages.

Thymocyte selection-associated high-mobility group box as a potential diagnostic marker differentiating hypopigmented mycosis fungoides from early vitiligo: A pilot study.

BACKGROUND: Hypopigmented mycosis fungoides is a rare variant of mycosis fungoides that may mimic many benign inflammatory hypopigmented dermatoses, and as yet there is no identified marker to differentiate between them. AIM: The aim of this study was to study the expression of thymocyte selection-associated high-mobility group box (TOX) in hypopigmented mycosis fungoides and one of its inflammatory mimickers (early active vitiligo) to assess its potential as a differentiating diagnostic marker. METHODS: A case-control study was done using immunohistochemical analysis of TOX expression in 15 patients with hypopigmented mycosis fungoides and 15 patients with early active vitiligo. Immunohistochemical analysis was done via a semi-quantitative method and an image analysis method. RESULTS: Hypopigmented mycosis fungoides showed a statistically significant higher expression of TOX than early active vitiligo. The expression of TOX was positive in a majority of hypopigmented mycosis fungoides cases (14 cases, 93.3%), while only one case (6.7%) of vitiligo was weakly positive. TOX also displayed 93.3% sensitivity and specificity, with a cut-off value of 1.5. LIMITATIONS: This was a pilot study testing hypopigmented mycosis fungoides against only a single benign inflammatory mimicker (early vitiligo). Other benign mimickers were not included. CONCLUSION: Our findings showed that TOX expression can differentiate hypopigmented mycosis fungoides from early active vitiligo which is one of its benign inflammatory mimickers, with a high degree of sensitivity and specificity.

Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment.

Acquired hypopigmented skin changes are commonly encountered by dermatologists. Although hypopigmentation is often asymptomatic and benign, occasional serious and disabling conditions present with cutaneous hypopigmentation. A thorough history and physical examination, centered on disease distribution and morphologic findings, can aid in delineating the causes of acquired hypopigmented disorders. The second article in this 2-part continuing medical education series focuses on conditions with a hypopigmented phenotype. Early diagnosis and appropriate management of these disorders can improve a patient's quality of life, halt disease progression, and prevent irreversible disability.

Perineural and intraneural cutaneous granulomas in granulomatous mycosis fungoides mimicking tuberculoid leprosy.

BACKGROUND: Histological similarities between granulomas and granulomatous mycosis fungoides (GMF) may lead to misdiagnoses of sarcoidosis or leprosy. METHODS: This report presents four patients with GMF in whom skin biopsies showed perineural and intraneural granulomas that were confused with tuberculoid leprosy granulomas. RESULTS: Patient 1 presented with erythematous plaques and bulky nodules. Biopsy findings suggested cutaneous sarcoidosis. Tumor resection showed granulomatous infiltrate extending to the fascia and skeletal muscle. Clinicopathological correlations permitted a diagnosis of GMF. Patient 2 presented with erythematous plaques. Skin biopsies had indicated sarcoidosis. Resection of a thigh nodule excluded leprosy, and GMF was diagnosed. Patient 3 presented with scaly, hyperpigmented plaques. Biopsy showed diffuse granulomatous inflammation with epithelioid and giant cells, abundant lymphocytes, and some eosinophils, and indicated GMF. Patient 4 presented with pruritic, erythematous plaques. Biopsy of an indurated mammary plaque initially indicated sarcoid granulomatous inflammation. Biopsy review suggested GMF. CONCLUSIONS: This study highlights both the diagnosis of GMF, and granulomatous cutaneous nerve injury in GMF and its possible confusion with leprosy granulomas. The histological diagnosis of GMF includes: (i) a granulomatous infiltrate rich in giant cells, emperipolesis, histiocytic cells, and scattered eosinophils, which may reach the fascia and muscle; (ii) the absence of elastic fibers or their phagocytosis by giant cells; and (iii) lymphocytes that may show atypia and epidermotropism. Deep biopsies reveal GMF diagnostic changes and, in conjunction with clinicopathological correlations, exclude a diagnosis of leprosy and support one of GMF, thus facilitating its appropriate management.

Keratoderma-like T cell dyscrasia: A report of 13 cases and its distinction from mycosis fungoides palmaris et plantaris.

BACKGROUND: Atypical epitheliotropic T cell lymphocytic infiltrates are commonly encountered in routine and consultative dermatopathology practices and typically do not represent mycosis fungoides. Other conditions can mimic certain light microscopic and phenotypic findings encountered in mycosis fungoides, comprising a diverse spectrum of conditions including the lymphomatoid drug reaction, collagen vascular disease, viral hypersensitivity reactions and cutaneous T cell dyscrasia. AIMS: To examine biopsies obtained from cutaneous T cell dyscrasia localized to the palms and soles and to evaluate whether it exhibits a morphologic and pathogenetic continuum with mycosis fungoides plantaris et palmaris. METHODS: We examined 13 biopsies showing an epidermotropic superficial lymphocytic infiltrate from thirteen patients who presented with a palmar and/or plantar keratoderma without other sites of cutaneous involvement. Conventional light microscopy, immunophenotyping and clonality studies were carried out. The clinical features were recorded. RESULTS: Biopsies showed a variably dense, superficial, angiocentric CD4 or CD8 dominant lymphocytic infiltrate accompanied by a non-destructive pattern of epidermotropism. Low-grade cerebriform atypia along with variable diminution in the expression of CD7 and CD62L was noted. In three cases, statins were suspected to be the cause. Due to lack of familiarity with the entity, treatment interventions were inconsistent and not aggressively pursued. There was no evidence of disease progression to mycosis fungoides in any case. LIMITATIONS: The limitations of this study include the lack of long-term follow up and information on the nature of the therapeutic interventions and responses to treatment. CONCLUSION: The spectrum of cutaneous lymphoid dyscrasias should be expanded to include cases manifesting as palmo-plantar keratoderma. These cases are to be distinguished from mycosis fungoides palmaris et plantaris. As with other forms of cutaneous lymphoid dyscrasia, the lesions tend to be persistent. The course however, is indolent in most cases.

Cutaneous annular lesions as the first sign of transformation of follicular lymphoma into diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with diverse clinical, pathological and genetic features. An 80-year-old woman was diagnosed with a stage IV-X-A (Ann Arbor staging system) low grade systemic follicular lymphoma (FL). Four months after the diagnosis, she developed asymptomatic, indurated, annular erythematous plaques with centrifugal growth on the abdomen, arms and neck. The skin biopsy revealed a dermal infiltration compatible with diffuse large B-cell lymphoma. Light chain restriction by flow cytometry was demonstrated. The variable, diverse and joining genes of immunoglobulin G heavy chains were sequenced and cloned, and showed the same pattern for both the initial follicular lymphoma and the skin infiltration. Translocation t (14;18) was present in both samples. Based on these findings, a diagnosis of transformation of follicular lymphoma into diffuse large B cell lymphoma was made. Although other hematological disorders such as primary cutaneous diffuse large B cell lymphoma, mycosis fungoides and the cutaneous infiltration of chronic juvenile myeloid leukemia can present as annular lesions, we were unable to find any previous reports of these as a manifestation of cutaneous infiltration by systemic non-Hodgkin lymphoma.

Phototherapy for mycosis fungoides.

BACKGROUND: Both phototherapy and photochemotherapy have been used in all stages of mycosis fungoides since they improve the symptoms and have a favourable adverse effect profile. MATERIALS AND METHODS: We performed an extensive search of published literature using keywords like "phototherapy", "photochemotherapy", "NBUVB", "PUVA", "UVA1", "mycosis fungoides", and "Sezary syndrome", and included systematic reviews, meta-analysis, national guidelines, randomized controlled trials (RCTs), prospective open label studies, and retrospective case series. These were then arranged according to their levels of evidence. RESULTS: Five hundred and forty three studies were evaluated, of which 107 fulfilled the criteria for inclusion in the guidelines. CONCLUSIONS AND RECOMMENDATIONS: Photochemotherapy in the form of psoralens with ultraviolet A (PUVA) is a safe, effective, and well tolerated first line therapy for the management of early stage mycosis fungoides (MF), that is, stage IA, IB, and IIA (Level of evidence 1+, Grade of recommendation B). The evidence for phototherapy in the form of narrow-band UVB (NB-UVB) is less robust (Level of evidence 2++, Grade of recommendation B) but may be considered at least as effective as PUVA in the treatment of early-stage MF as an initial therapy. In patients with patches and thin plaques, NB-UVB should be preferentially used. PUVA may be reserved for patients with thick plaques and those who relapse after initial NB-UVB therapy. For inducing remission, three treatment sessions per week of PUVA phototherapy or three sessions per week of NB-UVB phototherapy may be advised till the patient achieves complete remission. In cases of relapse, patients may be started again on PUVA monotherapy or PUVA may be combined with adjuvants like methotrexate and interferon (Level of evidence 2+, Grade of recommendation B). Patients with early-stage MF show good response to combination treatments like PUVA with methotrexate, bexarotene or interferon-α-2b. However, whether these combinations hold a significant advantage over monotherapy is inconclusive. For late stage MF, the above-mentioned combination therapy may be used as first-line treatment (Level of evidence 3, Grade of recommendation C). Currently, there is no consensus regarding maintenance therapy with phototherapy once remission is achieved. Maintenance therapy should not be employed for PUVA routinely and may be reserved for patients who experience an early relapse after an initial course of phototherapy (Level of evidence 2+, Grade of recommendation B). Bath-water PUVA may be tried as an alternative to oral PUVA in case the latter cannot be administered as the former may show similar efficacy (Level of evidence 2-, Grade of recommendation C). In pediatric MF and in hypopigmented MF, both NB-UVB and PUVA may be tried (Level of evidence 3, Grade of recommendation D).

Childhood hypopigmented mycosis fungoides: a commonly delayed diagnosis.

Primary cutaneous lymphomas (PCLs) are exceedingly rare in children and adolescents, with mycosis fungoides (MF) being the most frequent PCL diagnosed in childhood. There are numerous unusual clinical variants of MF, including the hypopigmented type form (HMF). HMF is exceptional overall, but comparatively common among children. We present an 8-year-old boy with a 3-year history of progressive, generalised, scaly, hypopigmented round patches and few erythematous papules. He was first diagnosed with pityriasis alba (PA), and moisturisers were prescribed with no improvement. Skin biopsy showed typical features of MF, and the patient was successfully treated with narrowband ultraviolet B. HMF may simulate atopic dermatitis, PA, pityriasis lichenoides, tinea versicolour, vitiligo, postinflammatory hypopigmentation or leprosy. Therefore, persistent and unusual hypopigmented lesions should be biopsied to rule out this rare variant of MF.

Borderline tuberculoid leprosy mimicking mycosis fungoides.

A 65-year-old unemployed man, originally from Michoacán and currently living in Toluca, state of Mexico, presented for medical consultation for disseminated dermatosis in all body segments. The condition was limited to the head and neck, was bilateral and symmetrical, and was characterized by infiltrated and confluent erythematous-edematous plates of diverse diameter covering 90% of the upper and lower extremities (Figure 1). The ailment had 2 years' evolution and a progressive course. The patient was diagnosed in private practice as having atopic dermatitis. After exacerbation of symptoms, he was treated with deflazacort and hydroxychloroquine with no improvement. Results from lesion biopsies revealed sarcoidal granulomas and the patient was therefore referred to the dermatology department at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán for further study and treatment with the presumptive diagnosis of mycosis fungoides vs sarcoidosis.

A study of clinicopathologic profile of 15 cases of hypopigmented mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is cutaneous lymphoma of the T-cell lineage. Hypopigmented MF is a clinical variant of MF, described mainly in Asians. This is a retrospective clinicopathologic analysis of hypopigmented MF at a tertiary care center. AIMS: To describe the clinicopathologic profile of hypopigmented MF. METHODS: Records of clinicopathologic notes over a 5-year period ranging from January 2005 up to December 2009 were reviewed over a period of 3 months, of which 15 cases were diagnosed with hypopigmented MF based on clinicopathologic correlation. RESULTS: Hypopigmented MF was found to be more common in males, and between second and fourth decades of life. The latent period between onset and diagnosis was around 3.83 years. Most of the patients were asymptomatic 80% (12/15), with skin changes of subtle atrophy in 46.66% (7/15), scaling in 20% (3/15) and focal changes of poikiloderma in 26.66% (4/15) patients. Most common sites of distribution of the lesions were the trunk and extremities. Many of the cases had been clinically mistaken for Hansen's disease prior to correct diagnosis. Marked epidermotropism and tagging of epidermis by large lymphocytes characterizes the condition histopathologically. Of the 15 cases, immunohistochemistry was possible in 10 cases, of which 8 showed predominant CD8 positive epidermotropic infiltrates and two cases showed absence of CD8 positive and CD4 positive lymphocytic infiltrate in the epidermis. CONCLUSION: Hypopigmented MF presents as hypopigmented asymptomatic patches without any erythema or infiltration in its early stage and mimics Hansen's disease. Skin biopsy clinches the diagnosis.

Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy.

We describe here a rare case of variant of mycosis fungoides (MF): ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG), IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

Granulomatous mycosis fungoides with large cell transformation misdiagnosed as leprosy.

BACKGROUND: Granulomatous mycosis fungoides is an unusual histopathological variant of cutaneous T-cell lymphoma without clinical distinction from classic mycosis fungoides. Symptoms associated with peripheral nerve involvement have rarely been reported in the literature. CASE REPORT: The authors described a case of granulomatous MF stage IIB with large cell transformation who initially presented with leprosy-like condition and chronic left peroneal neuropathy The patient received six courses ofgemcitabine with greater than 90% improvement of skin lesions. The rest of the lesions were successfully treated with local electron beam radiation. CONCLUSION: Granulomatous MF with neuropathy can be clinically misdiagnosed if there is no histopathological and immunohistochemical finding to support the diagnosis of lymphoma.

Granulomatous mycosis fungoides with hypohidrosis mimicking lepromatous leprosy.

Granulomatous mycosis fungoides (GMF) is a rare type of cutaneous T cell lymphoma. A 38-year-old married male presented with decreased sweating all over the body for last 8 years, progressive redness and scaling over body for 2 years and multiple noduloulcerative lesions over the body for 1 year. Cutaneous examination revealed generalized erythema and scaling with poikilodermatous changes over chest and upper back along with multiple noduloulcerative lesions. Skin biopsy from a nodular lesion revealed dense granulomatous infiltrate of atypical lymphocytes with epidermotropism and sparing of appendages. Diagnosis of GMF was made. Computed tomographic scan of thorax, abdomen and pelvis revealed axillary and inguinal lymphadenopathy. Immunohistochemistry revealed leukocyte common antigen and CD3 positivity suggestive of T cell origin. Patient was started on CHOP (Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisolone) regimen of chemotherapy with marked improvement after three cycles of chemotherapy. This case had some clinical resemblance to lepromatous leprosy.

Comparison of seropositivity of human T lymphotropic virus type 1 in mycosis fungoides patients and normal volunteers: a case-control study and review of literature.

BACKGROUND: There have been controversial reports about the possible association between mycosis fungoides (MF), its leukemic variant Siotazary syndrome (SS) and human T lymphotropic virus type 1 (HTLV-1) in different geographical regions. AIMS: The purpose of this study was to explore any association between MF and presence of HTLV-1 infection in Iran. METHODS: In a case-control setting, 150 clinically and histopathologically proven MF patients had been admitted to the tertiary referral skin center during a 10-year period and another 150 normal volunteers had been compared with each other for the presence of HTLV-1 infection. Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies against HTLV-1, and positive results were confirmed with western blotting. RESULTS: Only three MF patients had HTLV-1 infection, whereas two cases of normal subjects had the infection (P > 0.05). The only three seropositive MF patients were male and from North-Eastern Iran. CONCLUSION: This study showed that MF does not correlate with HTLV-1 infection in Iran.