Diagnostic challenge of mycosis fungoides: a case report of progression in a 46-year-old Filipino woman

Introduction

Background

Cutaneous T-cell lymphomas (CTCL) encompass a broad array of dermatological disorders characterized by aberrant T-cell proliferation within the skin. Intricate interplay between genetic predisposition and environmental factors underscores the complexity of CTCL pathogenesis (1). According to epidemiologic data, CTCL has an estimated incidence of approximately 6.4 cases per million population, with mycosis fungoides (MF) and Sézary syndrome (SS) accounting for nearly two-thirds of cases (2). In its classic form, MF typically exhibits erythematous patches and/or plaques that can progress to tumors or erythroderma, initially appearing in areas protected from sunlight such as the breasts, buttocks, lower trunk, and inguinal regions (3). It predominantly affects males and older adults, and is more frequently reported among African Americans (2). In the Philippines, a tertiary hospital-based study reported that mycosis fungoides accounted for 2.87 cases per 100,000 patients with histopathologically diagnosed skin tumors, with a median age of 49 years, underscoring that CTCL, while rare, remains a clinically relevant entity in the local setting (4).

Rationale and knowledge gap

Despite advances in diagnostic techniques, MF remains challenging to diagnose in its early stages due to its indolent course and close clinical and histopathologic resemblance to benign inflammatory dermatoses such as eczema or psoriasis (5). Furthermore, MF is more commonly observed in males, making reports in middle-aged Filipino women exceptionally uncommon. This gap underscores the need to document atypical presentations, enhance clinical awareness, and improve diagnostic vigilance.

MF slowly progresses from patch to plaque and tumor stages, although not all patients follow this sequence (6). Delayed diagnosis may result in disease progression to advanced stages, which are associated with poorer prognosis and the need for systemic therapy.

Objective

This case report aims to describe the progression from contact dermatitis to MF in a middle-aged Filipino woman, highlighting the diagnostic challenges, histopathologic and immunohistochemical findings, treatment course, and clinical outcome. By presenting this case, we seek to enrich and diversify the literature and emphasize the importance of a multidisciplinary approach to early recognition and management of MF. We present this article in accordance with the CARE reporting checklist (available at https://aol.amegroups.com/article/view/10.21037/aol-25-13/rc).

Case presentation

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the institutional ethics committee of Jose R. Reyes Memorial Medical Center (IRB No. 2025-007). Written informed consent was obtained from the patient’s husband for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A 46-year-old, female, Filipino, food vendor from Manila presented with a one-year history of pruritic erythematous patches and plaques on bilateral cheeks and forearms with no noted triggers nor aggravating factors. The patient had no fever, abdominal pain, or weight loss. She was incidentally diagnosed with chronic hepatitis B, low replication with no current treatment. She has no known allergies. She had no history of surgeries, injuries, accidents, or blood transfusions. She has not been on any maintenance medication or supplement. She has no history of prolonged exposure to ionizing radiation. She has no family history of cancer or autoimmune diseases. She was assessed as having allergic contact dermatitis, etiology to be determined and was treated with topical clobetasol propionate 0.05% lotion twice a day for 2 weeks with noted improvement of lesions and resolution of pruritus (April 2022). Interval history revealed recurrence of pruritic erythematous patches and plaques on her face, trunk and extremities; hence patch testing was done and was negative for all 30 haptens tested. Persistence of some erythematous patches, some of which evolved into plaques, warranted a skin biopsy of the lower back, which showed findings consistent with contact dermatitis (Figure 1).

Figure 1 Focal parakeratosis of the stratum corneum with irregular acanthosis and focal spongiosis of the epidermis. The upper dermis shows edema with moderate superficial perivascular lymphocytic infiltrates admixed with few eosinophils and dilated blood vessels (hematoxylin-eosin stain, ×40).

The patient was still managed with topical clobetasol propionate 0.05% lotion twice a day for two weeks and reported resolution of patches and plaques on her trunk and extremities but noted persistence of the plaque on the cheek. Hence, repeat biopsy was done (January 2023) on the cheek which revealed parapsoriasis (Figure 2).

Figure 2 Orthokeratosis of the stratum corneum with an atrophic epidermis showing basal layer hyperpigmentation and focal basal vacuolar change. The dermis demonstrates dense superficial and deep perivascular and periadnexal infiltrates of lymphocytes and histiocytes with numerous melanophages; some lymphocytes exhibit cytologic atypia with hyperchromatic nuclei, and blood vessels are dilated (hematoxylin-eosin stain, ×20).

The patient was given topical clobetasol propionate 0.05% lotion twice a day for 2 weeks and narrowband ultraviolet B (NBUVB) phototherapy three times weekly, with doses escalated from 360 mJ/cm² to a maximum of 1,305 mJ/cm². However, she noted appearance and persistence of multiple plaques on the back, as well as a nodule on the forehead despite topical clobetasol propionate 0.05% lotion and NBUVB phototherapy (Figure 3). Skin punch biopsy was done (June 2023) on the back and forehead, which revealed CTCL (Figure 4). Alcian blue stain highlighted pools of mucin inside follicular structures, while CD3 and CD20 stains were positive (Figure 5).

Figure 3 Clinical photographs after treatment of topical clobetasol propionate 0.05% lotion and narrowband ultraviolet B phototherapy, which were used as biopsy sites. (A) Multiple erythematous plaques on the back. (B) Nodule on the forehead. The images were published with the patient’s consent.

Figure 4 Histopathologic findings from skin punch biopsies of the back and forehead. (A) Orthokeratosis of the stratum corneum with an atrophic epidermis. The arrow shows the dermis with diffuse infiltrates of small- to medium-sized lymphocytes, histiocytes, and eosinophils surrounding blood vessels and adnexal structures (hematoxylin-eosin stain, ×30). (B) Orthokeratosis of the stratum corneum with focal scale crust. The arrow shows the epidermis with spongiosis and focal basal layer vacuolization, scattered dyskeratotic cells, and lymphocyte exocystosis. The dermis shows nodular dense periadnexal infiltrates of small- to medium-sized lymphocytes, histiocytes, and eosinophils extending into the subcutaneous layer, with swollen and distorted hair follicles (hematoxylin-eosin stain, ×20).

Figure 5 Immunohistochemical characterization of infiltrates. (A) Dense lymphocytic infiltrates predominantly composed of T cells highlighted by CD3 immunostaining (CD3 stain, ×40). (B) B cells highlighted by CD20 immunostaining within the dermal infiltrates (CD20 stain, ×40).

Baseline laboratory evaluation revealed leukocytosis (16.0×10⁹/L; normal range: 5.0–11.0 ×10⁹/L) with eosinophilia (8.3%; normal range: 1–3%), while hemoglobin, platelet count, renal function, electrolytes, and liver enzymes were within normal limits. Lactate dehydrogenase was elevated (467 U/L; normal range: 135–214 U/L). Serologic testing showed chronic hepatitis B infection with low viral replication (HBsAg reactive, anti-HBc IgG reactive, anti-HBc IgM non-reactive, hepatitis B virus DNA 258 IU/mL). Human immunodeficiency virus and hepatitis C serologies were negative, and antinuclear antibody testing was negative. Coagulation profile and urinalysis were unremarkable, and sputum GeneXpert testing for Mycobacterium tuberculosis was negative.

Fluorodeoxyglucose positron emission tomography-computed tomography scan (July 2023) showed multiple areas of increased metabolic activity in the skin, primarily on the right side, which are likely associated with the CTCL. Additionally, there were hypermetabolic lymph nodes in the left axilla and bilateral groin, along with smaller nodes in the neck, indicating possible secondary involvement by malignant lymphoma. It revealed diffuse low metabolic activity in the bones and pelvis, which could be due to either malignant infiltration or inflammation (Figure 6). Inguinal lymph node biopsy showed reactive hyperplasia (August 2023). Bone marrow core needle biopsy showed fibro-osseous and fibrocartilaginous tissue. No bone marrow tissue seen (September 2023). The patient was diagnosed with MF, stage IIB (T3N1aM0B0).

Figure 6 Fluorodeoxyglucose positron emission tomography-computed tomography scan results.

She then presented with multiple well-defined to ill-defined, irregularly shaped erythematous to hyperpigmented nodules and plaques some with crusting and xerosis on face, trunk, both upper and lower extremities and both palms and soles and palpable nontender lymph nodes on the right cervical, left axillary, and right inguinal area (Figure 7).

Figure 7 Clinical photographs showing multiple erythematous plaques on the back (A), nodules on the forehead (B) and plaques and nodules on the legs (C,D) after treatment of topical tretinoin 0.05% cream and narrowband ultraviolet B phototherapy. The images were published with the patient’s consent.

She was treated with topical betamethasone valerate 0.1% lotion twice a day for 2 weeks, then once a day for the next 2 weeks, with minimal improvement. Due to persistence of lesions, she was shifted to tretinoin cream once at night for 1 month with minimal improvement. NBUVB phototherapy three times weekly, with doses escalated from 360 mJ/cm² to a maximum of 1,305 mJ/cm² over 116 sessions, for a cumulative dose of 138,531 mJ/cm². She was treated with external beam radiation therapy with partial response.

Despite compliance with the regimen, there were noted new plaques and nodules on the face, trunk and extremities. She was referred back to the Hematology Department and was started on methotrexate 10 mg per week for 1 month (January 2024). However, there was still progression of cutaneous nodules, and the patient was lost to follow-up (February 2024). Fluorodeoxyglucose positron emission tomography-computed tomography scan (June 2024) showed interval progression in size and hypermetabolic features on left palatine tonsil, bilateral cervical, axillary, mediastinal and hilar, right external iliac and bilateral inguinal lymphadenopathies and multiple hypermetabolic bilateral lower extremity cutaneous/dermal, subcutaneous and intramuscular lesions. CD30 stain was requested, which revealed negative result. The patient was still lost to follow-up. Due to febrile episodes accompanied with a productive cough, the patient sought consultation at a nearby hospital and was diagnosed with pneumonia. She was admitted, however, she subsequently died (July 2024). The entire treatment timeline reported by the patient and relatives during the treatment is summarized in Figure 8.

Figure 8 Timeline and duration of each treatment. The images were published with the patient’s consent. PET-CT, positron emission tomography-computed tomography.

Discussion

Key findings

This case highlights a diagnostically challenging progression from clinically and histopathologically documented contact dermatitis to parapsoriasis to MF in a middle-aged Filipino woman. The patient initially responded to topical corticosteroids, consistent with inflammatory dermatoses, but subsequently developed persistent and progressive lesions refractory to standard therapy. Serial biopsies demonstrated evolving histopathologic features—from contact dermatitis to parapsoriasis and finally MF—underscoring the dynamic nature of early MF and the limitations of single time-point histologic assessment. The patient’s eventual diagnosis of stage IIB disease with tumor formation and nodal involvement reflects the potential consequences of delayed recognition.

Strengths and limitations

The primary strength of this report lies in its detailed longitudinal documentation, including serial biopsies, clinicopathologic correlation, advanced imaging, and treatment initiations, which collectively illustrate the evolution of MF from an inflammatory mimic. This report adds to the limited literature on dermatitis-like presentations progressing to MF, particularly in a Southeast Asian female population. However, this report is limited by the absence of molecular studies assessing T-cell clonality during early disease stages and by the restricted number of immunohistochemical stains performed, a constraint commonly encountered in low to middle-income countries such as the Philippines. These limitations may have further clarified the timing and nature of malignant transformation.

Comparison with similar research

Progression from contact dermatitis to MF only has limited reports and a small number of case series describing dermatitis-like presentations that were ultimately reclassified as MF on repeat biopsy (7-9). Atopic dermatitis, which can mimic contact dermatitis, has occasionally been associated with MF, and treatments like dupilumab may unmask previously undiagnosed disease (10). Another study reported four patients with long-standing chronic dermatitis who later developed histologically confirmed MF after a latency period of 5 to 9 years. Duration of dermatitis prior to MF ranged from 2 months to 15 years, and in two cases, contact allergens such as nickel, potassium dichromate, and formaldehyde were identified through patch testing. They proposed that persistent antigenic stimulation from chronic dermatitis may contribute to malignant T-cell clonality and eventual lymphomatous transformation (9).

Compared with these cases, this report demonstrated an accelerated clinical course, with progression from contact dermatitis to parapsoriasis and MF occurring over approximately one year. This highlights the heterogeneity in disease evolution and underscores that malignant transformation may occur more rapidly than previously recognized, particularly when early lesions are repeatedly treated as benign inflammatory dermatoses.

In a 26-year retrospective cohort study of 105 patients, about 35% of those with large plaque parapsoriasis progressed to histologically confirmed MF within a median period of 6 years. Furthermore, small plaque parapsoriasis, long considered benign, demonstrated a 10% progression rate to MF over a median of 10 years (11).

Explanation of findings

Data from the Philippines (2011–2023) show 471 newly diagnosed CTCL cases, with a male predominance (274 males, 197 females). The highest incidence occurred in the 61–70 age group, followed by 71–80 and 21–30 years. Pediatric cases (1–10 years) numbered 18, and those in the 81–90 years group numbered 13, with no cases in infants or those over 91. Case numbers peaked in 2011 (43 cases) and 2014 (41 cases) and were lowest in 2015 and 2020 (<13 cases each) (12).

Diagnosing MF, particularly in its early stage, is challenging because it closely resembles several more common skin conditions, with subtle histopathological distinctions. These include spongiotic dermatitis (primarily eczema), lichenoid dermatitis, chronic superficial scaly dermatitis, and pigmented purpuric dermatoses (13,14).

In histopathology, MF is characterized by epidermotropism, atypical lymphocytes, and Pautrier’s microabscesses compared to benign conditions showing spongiosis without nuclear atypia. Immunohistochemical analysis typically shows an elevated CD4:CD8 ratio with loss of CD7. Molecular tests, such as T-cell receptor gene rearrangement, can confirm clonality, which supports a diagnosis of MF. Furthermore, the International Society for Cutaneous Lymphomas (ISCL) and European Organization for Research and Treatment of Cancer (EORTC) guidelines recommend combining clinical, histopathological, and molecular data for accurate diagnosis (15).

In the early stages of MF (stages IA–IIA), prognosis is generally positive, and treatment mainly revolves around skin-directed therapies. These treatments may involve topical steroids, retinoids/rexinoids, psoralen plus ultraviolet A (PUVA) or NBUVB phototherapy, topical nitrogen mustard, spot radiation, and total skin electron beam therapy. For advanced-stage MF/SS (stages IIB–IVB), the aim is to reduce tumor size, delay disease progression, and maintain quality of life. Commonly used first-line monotherapies include biological agents such as interferon-alpha, retinoids, rexinoids (e.g., bexarotene), and low-dose methotrexate. These therapies may also be combined with skin-directed treatments for early-stage disease that does not respond well (3).

Patients who receive early comprehensive therapy, including phototherapy, radiation, or systemic agents tailored to disease stage, often achieve durable responses. Patients who received phototherapy had a longer median time to tumor progression and survived longer than those who did not (16). NBUVB phototherapy is an effective first-line therapy for early-stage MF, offering safety advantages over broadband ultraviolet B and PUVA, with PUVA reserved for nonresponders or disease progression. Systemic therapies including retinoids, interferon-alpha, bexarotene, and low-dose methotrexate can stabilize disease, but response rates vary (17-19).

The strongest prognostic factor in MF is disease stage, with T stage and the presence of extracutaneous involvement being the most important determinants of survival (20). Patients with localized or generalized patches or plaques (stage IA–IIA, early-stage) generally have an indolent course, with a 10-year overall survival exceeding 70%. In contrast, patients presenting with skin tumors, erythroderma, or extracutaneous disease (stage IIB–IVB, advanced-stage) have a markedly reduced 10-year overall survival of less than 30% (21). A large-cell phenotype at diagnosis is associated with a more favorable prognosis, while age over 60, male gender, presence of plaques, folliculotropism, eosinophilia, and extracutaneous disease predict worse outcomes. Elevated lactate dehydrogenase levels correlate with advanced tumor stages, and emerging molecular markers, such as KIR3DL2, have been linked to malignant transformation (20).

Implications and actions needed

Accurate diagnosis of early-stage MF may require repeated or multiple biopsies from different representative lesions, particularly when initial histopathology is inconclusive. To optimize pathological evaluation, topical treatments should be discontinued 2 to 4 weeks prior to biopsy, allowing the characteristic histologic features to become more apparent (21). Patients with cutaneous lymphoma should be educated to regularly examine their skin and palpate lymph nodes. Follow-up schedules should be individualized based on disease stage, subtype, treatment received, and overall clinical status, and maintained lifelong. While standardized guidelines are limited, recommendations from European Society for Medical Oncology suggest monitoring patients with stable or indolent disease, or those in complete remission, every 6–12 months, whereas patients with active or progressive disease should be seen every 4–6 weeks (22).

This reinforces the need for heightened clinical suspicion when dermatitis-like lesions persist, recur, or progress despite appropriate therapy. Dermatologists should consider repeat biopsies from evolving or treatment-resistant lesions and pursue multidisciplinary collaboration with dermatopathology and hematology. Early integration of immunohistochemical and molecular studies may facilitate earlier diagnosis and staging, potentially improving outcomes.

Conclusions

This case involves a 46-year-old Filipino female with a presentation of erythematous patches to plaques on extremities with initial biopsy results showing allergic contact dermatitis, followed by parapsoriasis, and ultimately diagnosed as CTCL.

MF can mimic more prevalent skin conditions such as eczema or psoriasis, potentially persisting undiagnosed for many years, even decades, due to its slow progression. Given the rarity of documented progressions and the potential for misdiagnosis, specific statistics on the number of contact dermatitis cases evolving into cutaneous lymphoma are not available based from our knowledge. If a skin condition persists or worsens despite appropriate treatment, further evaluation by a dermatologist is advisable to rule out underlying malignancies. Accurate diagnosis, staging, and risk assessment of MF necessitate a multidisciplinary approach.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aol.amegroups.com/article/view/10.21037/aol-25-13/rc

Peer Review File: Available at https://aol.amegroups.com/article/view/10.21037/aol-25-13/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aol.amegroups.com/article/view/10.21037/aol-25-13/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This paper was approved by the institutional ethics committee of Jose R. Reyes Memorial Medical Center (IRB No. 2025-007). Written informed consent was obtained from the patient’s husband for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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