EXTRAORDINARY CASE REPORT
Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis Erica Riveiro-Falkenbach, MD, PhD,* Yolanda Ruano, PhD,* Maria Garrido, MD, PhD,* Pablo L. Ortiz-Romero, MD, PhD,† and José Luis Rodríguez-Peralto, MD, PhD*
Abstract: Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. This entity may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses. Among its histopathological variants, spongiosis is an infrequent finding, and spongiotic microvesiculation is particularly rare. Mucinous deposition is a common event in folliculosebaceous units of folliculotropic MF but rarely described within the epidermis. Herein, we report a patient with eczematous palmoplantar lesions whereby the histological, immunohistochemical, and molecular studies confirmed to be a unique case of MF showing epidermal microvesiculation mucinosis. Key Words: mycosis fungoides, epidermal microvesiculation mucinosis, acral lesions (Am J Dermatopathol 2015;37:632–634)
CASE REPORT A 47 year-old male presented to the Department of Dermatology with a 5-year history of erythematous papules and plaques on the face and trunk. The biopsy of the follicular papule of the chin led to the diagnosis of folliculotropic mycosis fungoides (MF). Molecular analysis of T-cell receptor gamma (TCR gamma) rearrangement through GeneScanning of polymerase chain reaction products1 detected 2 monoclonal peaks at 184 and 219 bp. One year after the diagnosis, the patient developed new lesions on the abdomen, which were diagnosed as MF with large cell transformation. Since the onset of symptoms, the patient presented eczematous palmoplantar lesions, negative for fungal culture and unresponsive to corticosteroids (Fig. 1). A biopsy of the plantar region was performed identifying a lymphocytic proliferation occupying the papillary dermis with epidermotropism and alignment on the basal layer of the epidermis. The epidermis also shows intercellular spaces and microvesicles containing a basophilic granular deposit, positive for colloidal iron staining. Intraepidermal and dermal lymphocytes are irregular, convoluted and express CD3, CD4, CD5, and CD43 (Fig. 2). Most of the cells are negative for CD8 and CD7. TCR gamma rearrangement of plantar lesion showed the same 2 monoclonal peaks (184 and 219 bp) detected in folliculotropic lesions of From the Departments of *Pathology, and †Dermatology, Hospital Universitario 12 de Octubre, Medical School, Universidad Complutense, Instituto de Investigación I+12, Madrid, Spain. E. Riveiro-Falkenbach is the recipient of a postdoctoral fellowship from “Fundación Científica de la Asociación Española Contra el Cáncer.” The remaining authors declare no conflicts of interest. Reprints: José Luis Rodríguez-Peralto, MD, PhD, Department of Pathology, Hospital Universitario 12 de Octubre, Universidad Complutense, Instituto de Investigación I+12, Madrid, Spain 28041 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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the face (Fig. 3). The palmoplantar lesions were thus diagnosed as MF with epidermal mucinosis and treated with corticosteroids under occlusion with partial clinical response.
DISCUSSION MF is the most common type of cutaneous T-cell lymphoma, which may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses.2 Among its histological variants, slight spongiosis might be seen in patch- or plaque-stage mycosis fungoids.3 However, the presence of substantial spongiosis and microvesiculation is extremely rare in MF.4 The study of 222 biopsies performed by Shapiro et al5 identified 6% of moderate spongiosis but no case of marked spongiosis. The precise mechanism of spongiosis in MF is unclear. In an attempt to elucidate its mechanism, Nickoloff6 studied 20 cases of MF with spongiotic appearance. Interestingly, they found that 19 of 20 biopsies presented colloidal ironpositive material between the intercellular spaces. Indeed, the degree of epidermal mucin deposition correlated with the degree of spongiosis.6 In this study, none of the cases presented microvesicles into the epidermis. Herein, we report a patient who presented with folliculotropic MF and eczematous palmoplantar lesions. The histological study of acral lesions identified the presence of intraepidermal microvesiculation with granular mucinous deposits, in which the presence of mucinous material was confirmed with colloidal iron stain. Although the finding of microvesiculation is rarely seen in mycosis fungoides, the diagnosis of acral MF was confirmed by the identification of atypical CD4+ lymphocytic infiltrate and monoclonal peaks of TCR gamma rearrangement. To our knowledge, this is the first report in the literature of a clinically long-standing acral “eczema,” whereby the histological, immunohistochemical, and molecular studies confirmed the diagnosis of MF with epidermal microvesiculation mucinosis. Taking into account the study of Nickoloff6 and this case report, we believe that the production of mucin could contribute mechanistically to spongiosis and microvesicular formation in mycosis fungoides. Indeed, the alteration in mucin deposition in the epidermis could provide pathways for the migration of transformed T lymphocytes.7 Additional studies are still necessary to elucidate the precise mechanism of spongiosis in MF. The presence of intraepidermal mucinosis is an interesting feature that could bring new insight into the physiopathology of mycosis fungoides. Am J Dermatopathol Volume 37, Number 8, August 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Acral Mycosis Fungoides
FIGURE 1. “Eczematous lesions” in palmoplantar regions in a patient with MF.
FIGURE 2. A and B, Panoramic and higher power views of the plantar lesion demonstrate lymphocytic epidermotropism, increment of epidermal intercellular spaces, and microvesiculation with granular and basophilic deposits. C, Colloidal iron stain shows positive material inside the epidermal vesicles. D, Immunoperoxidase staining reveals that the majority of atypical cells stain with CD4.
FIGURE 3. Molecular analysis for T-cell receptor gamma rearrangement of folliculotropic lesion on the face (top) and plantar lesion (bottom). The amplified fragments were analyzed by fluorescent capillary electrophoresis (GeneScanning). Two monoclonal peaks were detected at 184 and 219 bp. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
633
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Riveiro-Falkenbach et al
REFERENCES 1. van Dongen JJ, Langerak AW, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–2317. 2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768–3785. 3. Ackerman AB. Mycosis fungoides: diagnosis and pretreatment evaluation of the patient: I. Light microscopy. Prog Dermatol. 1982;16:1–3.
4. LeBoit PE. Variants of mycosis fungoides and related cutaneous T-cell lymphomas. Semin Diagn Pathol. 1991;8:73–81. 5. Shapiro PE, Pinto FJ. The histologic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes. Am J Surg Pathol. 1994;18:645–667. 6. Nickoloff BJ. Epidermal mucinosis in mycosis fungoides. J Am Acad Dermatol. 1986;15:83–86. 7. Reed RJ. The T-lymphocyte, the mucinous epithelial interstitium, and immunostimulation. Am J Dermatopathol. 1981;3:207–214.
634
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
| www.amjdermatopathology.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Acral Mycosis Fungoides With Epidermal Microvesiculation Mucinosis Erica Riveiro-Falkenbach, MD, PhD,* Yolanda Ruano, PhD,* Maria Garrido, MD, PhD,* Pablo L. Ortiz-Romero, MD, PhD,† and José Luis Rodríguez-Peralto, MD, PhD*
Abstract: Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. This entity may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses. Among its histopathological variants, spongiosis is an infrequent finding, and spongiotic microvesiculation is particularly rare. Mucinous deposition is a common event in folliculosebaceous units of folliculotropic MF but rarely described within the epidermis. Herein, we report a patient with eczematous palmoplantar lesions whereby the histological, immunohistochemical, and molecular studies confirmed to be a unique case of MF showing epidermal microvesiculation mucinosis. Key Words: mycosis fungoides, epidermal microvesiculation mucinosis, acral lesions (Am J Dermatopathol 2015;37:632–634)
CASE REPORT A 47 year-old male presented to the Department of Dermatology with a 5-year history of erythematous papules and plaques on the face and trunk. The biopsy of the follicular papule of the chin led to the diagnosis of folliculotropic mycosis fungoides (MF). Molecular analysis of T-cell receptor gamma (TCR gamma) rearrangement through GeneScanning of polymerase chain reaction products1 detected 2 monoclonal peaks at 184 and 219 bp. One year after the diagnosis, the patient developed new lesions on the abdomen, which were diagnosed as MF with large cell transformation. Since the onset of symptoms, the patient presented eczematous palmoplantar lesions, negative for fungal culture and unresponsive to corticosteroids (Fig. 1). A biopsy of the plantar region was performed identifying a lymphocytic proliferation occupying the papillary dermis with epidermotropism and alignment on the basal layer of the epidermis. The epidermis also shows intercellular spaces and microvesicles containing a basophilic granular deposit, positive for colloidal iron staining. Intraepidermal and dermal lymphocytes are irregular, convoluted and express CD3, CD4, CD5, and CD43 (Fig. 2). Most of the cells are negative for CD8 and CD7. TCR gamma rearrangement of plantar lesion showed the same 2 monoclonal peaks (184 and 219 bp) detected in folliculotropic lesions of From the Departments of *Pathology, and †Dermatology, Hospital Universitario 12 de Octubre, Medical School, Universidad Complutense, Instituto de Investigación I+12, Madrid, Spain. E. Riveiro-Falkenbach is the recipient of a postdoctoral fellowship from “Fundación Científica de la Asociación Española Contra el Cáncer.” The remaining authors declare no conflicts of interest. Reprints: José Luis Rodríguez-Peralto, MD, PhD, Department of Pathology, Hospital Universitario 12 de Octubre, Universidad Complutense, Instituto de Investigación I+12, Madrid, Spain 28041 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
632
| www.amjdermatopathology.com
the face (Fig. 3). The palmoplantar lesions were thus diagnosed as MF with epidermal mucinosis and treated with corticosteroids under occlusion with partial clinical response.
DISCUSSION MF is the most common type of cutaneous T-cell lymphoma, which may present with a wide spectrum of clinicopathological manifestations and mimic different dermatoses.2 Among its histological variants, slight spongiosis might be seen in patch- or plaque-stage mycosis fungoids.3 However, the presence of substantial spongiosis and microvesiculation is extremely rare in MF.4 The study of 222 biopsies performed by Shapiro et al5 identified 6% of moderate spongiosis but no case of marked spongiosis. The precise mechanism of spongiosis in MF is unclear. In an attempt to elucidate its mechanism, Nickoloff6 studied 20 cases of MF with spongiotic appearance. Interestingly, they found that 19 of 20 biopsies presented colloidal ironpositive material between the intercellular spaces. Indeed, the degree of epidermal mucin deposition correlated with the degree of spongiosis.6 In this study, none of the cases presented microvesicles into the epidermis. Herein, we report a patient who presented with folliculotropic MF and eczematous palmoplantar lesions. The histological study of acral lesions identified the presence of intraepidermal microvesiculation with granular mucinous deposits, in which the presence of mucinous material was confirmed with colloidal iron stain. Although the finding of microvesiculation is rarely seen in mycosis fungoides, the diagnosis of acral MF was confirmed by the identification of atypical CD4+ lymphocytic infiltrate and monoclonal peaks of TCR gamma rearrangement. To our knowledge, this is the first report in the literature of a clinically long-standing acral “eczema,” whereby the histological, immunohistochemical, and molecular studies confirmed the diagnosis of MF with epidermal microvesiculation mucinosis. Taking into account the study of Nickoloff6 and this case report, we believe that the production of mucin could contribute mechanistically to spongiosis and microvesicular formation in mycosis fungoides. Indeed, the alteration in mucin deposition in the epidermis could provide pathways for the migration of transformed T lymphocytes.7 Additional studies are still necessary to elucidate the precise mechanism of spongiosis in MF. The presence of intraepidermal mucinosis is an interesting feature that could bring new insight into the physiopathology of mycosis fungoides. Am J Dermatopathol Volume 37, Number 8, August 2015
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Acral Mycosis Fungoides
FIGURE 1. “Eczematous lesions” in palmoplantar regions in a patient with MF.
FIGURE 2. A and B, Panoramic and higher power views of the plantar lesion demonstrate lymphocytic epidermotropism, increment of epidermal intercellular spaces, and microvesiculation with granular and basophilic deposits. C, Colloidal iron stain shows positive material inside the epidermal vesicles. D, Immunoperoxidase staining reveals that the majority of atypical cells stain with CD4.
FIGURE 3. Molecular analysis for T-cell receptor gamma rearrangement of folliculotropic lesion on the face (top) and plantar lesion (bottom). The amplified fragments were analyzed by fluorescent capillary electrophoresis (GeneScanning). Two monoclonal peaks were detected at 184 and 219 bp. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.amjdermatopathology.com |
633
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Riveiro-Falkenbach et al
REFERENCES 1. van Dongen JJ, Langerak AW, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–2317. 2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768–3785. 3. Ackerman AB. Mycosis fungoides: diagnosis and pretreatment evaluation of the patient: I. Light microscopy. Prog Dermatol. 1982;16:1–3.
4. LeBoit PE. Variants of mycosis fungoides and related cutaneous T-cell lymphomas. Semin Diagn Pathol. 1991;8:73–81. 5. Shapiro PE, Pinto FJ. The histologic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes. Am J Surg Pathol. 1994;18:645–667. 6. Nickoloff BJ. Epidermal mucinosis in mycosis fungoides. J Am Acad Dermatol. 1986;15:83–86. 7. Reed RJ. The T-lymphocyte, the mucinous epithelial interstitium, and immunostimulation. Am J Dermatopathol. 1981;3:207–214.
634
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
| www.amjdermatopathology.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
