Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Quiz
89 (
2
); 283-286
doi:
10.25259/IJDVL_1200_20
pmid:
34379962

Rapidly progressive hyperpigmented keratotic plaques with epidermotropism

Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
Corresponding author: Dr. Vishal Gupta, Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India. doctor.vishalgupta@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Taneja N, Dev T, Patel U, Arava S, Gogia A, Gupta V. Rapidly progressive hyperpigmented keratotic plaques with epidermotropism. Indian J Dermatol Venereol Leprol 2023;89:283-6.

A 47-year-old, otherwise healthy man presented with multiple hyperpigmented plaques on his trunk and extremities. The plaques were first noticed on the trunk five months back which subsequently involved the extremities. He had no systemic complaints. On cutaneous examination, we noted numerous round-to-oval hyperpigmented keratotic papules and mildly scaly plaques (size 1-5 cm) on the trunk and extremities [Figure 1a]. The truncal and lower limb plaques were larger, with some showing superficial ulceration and annular configuration [Figure 1b]. There was prominent palmoplantar involvement, with coalescing keratotic papules and plaques on the soles [Figure 1c]. Routine laboratory investigations including complete blood count, serum biochemistry and lactate dehydrogenase levels (143 U/L) were within normal limits. A punch skin biopsy was performed from keratotic plaques over the abdomen and sole.

Figure 1a:
Hyperpigmented papules and plaques on the trunk. Some plaques show central ulceration
Figure 1b:
Ulcerated plaques arranged in an annular configuration around a resolving plaque
Figure 1c:
Confluent plaques over bilateral soles; few plaques on the right sole are ulcerated

Question

What is your diagnosis?

Answer

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma

Discussion

Skin biopsies showed irregularly acanthotic epidermis with dense diffuse pan-dermal infiltrate of lymphocytes and histiocytes. There were scattered large and atypical lymphocytes in the epidermis, present singly and in clusters forming microabscesses [Figures 2a and b]. We observed mild-to-moderate epidermal spongiosis and focal spongiotic vesicles, along with few necrotic keratinocytes [Figures 2c and d]. The lymphocytes were strongly immunopositive for CD3 and CD8 [Figure 3a], focally positive for CD4 [Figure 3b] and negative for CD20 and CD30. Peripheral blood examination and bone marrow biopsy were unremarkable. 18-fluorodeoxyglucose whole body positron emission tomography scan demonstrated metabolically active uptake limited to cutaneous and soft-tissue lesions. The patient was treated with methotrexate (15–30 mg/week) for three months, followed by all-trans-retinoic acid (80 mg/day) for a month without much improvement. Subsequently, pegylated doxorubicin (50 mg/month) was administered with partial flattening of the plaques. Six months following treatment, the disease worsened with multiple new plaques and new-onset bullous lesions and crusted erosions, with immunohistological features of aggressive epidermotropic CD8+ T-cell lymphoma. He was subsequently administered one cycle of gemcitabine (1.2 g/m2) and oral prednisolone 40 mg/day, however, COVID-19 lockdown prevented further follow-up visits. We lost the patient after three months due to worsening of skin lesions and general condition.

Figure 2a:
Skin biopsy from abdomen showing lymphocytes in the epidermis, both singly and in a few clusters, with minimal spongiosis (epidermotropism) (hematoxylin and eosin, ×100)
Figure 2b:
Higher magnification shows the lymphocytes to be large, pleomorphic and atypical; a necrotic keratinocyte is also visible (hematoxylin and eosin, ×400)
Figure 2c:
Skin biopsy from sole shows clusters of atypical lymphocytes (Pautrier microabscesses) in the epidermis (hematoxylin and eosin, ×200)
Figure 2d:
Another focus from the same biopsy shows epidermal spongiosis with spongiotic blisters as well as lymphocyte epidermotropism (hematoxylin and eosin, ×100)
Figure 3a:
Immunohistochemistry showing strong CD8 expression in lymphocytes (×40)
Figure 3b:
Immunohistochemistry showing focally positive CD4 lymphocytes (×40)

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma represents less than 1% of all cutaneous T-cell lymphomas and is included as a provisional entity in the latest WHO/EORTC classification.1 It was referred to as “Berti’s lymphoma,” “generalized pagetoid reticulosis,” or “Ketron-Goodman disease” before the category of primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma was established.2-4 It is characterized by rapidly progressing disseminated patches, papules, plaques, nodules and tumors with central necrosis and ulceration.4 There is a propensity for visceral metastasis to lung, testis, central nervous system and oral mucosa, but lymph nodes are often spared. However, skin-limited disease has been reported rarely, similar to our case.5 Histological features include dense dermal lymphocytic infiltrates, with marked pagetoid epidermotropism composed of pleomorphic small- to medium-sized T-cells. The neoplastic T-cells have a CD8+/CD4- cytotoxic T-cell profile with granzyme B, perforin and TIA-1 marker expression.6 Conventional therapies for cutaneous T-cell lymphomas are generally ineffective, while interferon-alpha and multiagent chemotherapy have been tried with unsatisfactory results.7,8 It has an aggressive clinical course and poor prognosis with a median survival of 12–32 months.4,7 Allogenic hematopoietic stem cell transplantation has induced partial or complete remission in few patients.4 A recent report has highlighted long-term remission with brentuximab vedotin monotherapy.9 In the absence of a standard accepted treatment for this lymphoma and skin-limited disease in our patient, we tried methotrexate initially, but later escalated to monoagent chemotherapies such as doxorubicin and gemcitabine due to inadequate response.

Apart from primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma, differential diagnoses of CD8+ lymphoproliferative disorders include CD8+ mycosis fungoides, pagetoid reticulosis, lymphomatosis papulosis type D, primary cutaneous acral CD8+ lymphoma and subcutaneous panniculitic T-cell lymphoma. Of these, CD8+ mycosis fungoides particularly can be a close differential diagnosis due to its clinical and histologic similarity (epidermotropism). Although both can present with plaques and ulcerated tumors, the verrucous or hyperkeratotic and annular morphology of plaques, accentuated palmoplantar involvement and rapid disease progression favour the diagnosis of primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. On histopathology, features such as spongiosis with spongiotic blisters, necrotic keratinocytes, deep dermal infiltrate, angio- and adnexotropism in addition to epidermotropism should raise the possibility of primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma [Table 1]. It is not unusual for these patients to be initially misdiagnosed as mycosis fungoides.4 Correct diagnosis of this aggressive lymphoma requires a strong clinicopathological correlation.

Table 1: Differences between primary cutaneous aggressive epidermotropic CD8+ T-Cell lymphoma and CD8+ mycosis fungoides
Features Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma CD8+ mycosis fungoides
Clinical features
History Short, weeks to months, rapid progression Long, months to years
Course Aggressive; rapidly fatal course with a median survival time of 12–32 months Indolent
Morphology of skin lesions Patches, plaques, verrucous or hemorrhagic papules, nodules and tumors
A few show annular plaques with peripheral erosions and central ulceration; some may show a spontaneous central resolution
Patches, plaques and nodules
Distribution of skin lesions Generalized
Acral accentuation
Photocovered area
Progression No sequential progression from patches to plaques to nodules Sequential progression from patches to plaques to nodules noted
Mucosal involvement Common Rare
Metastasis Common, early
Spares lymph nodes
Involves lung, testes, CNS and
oral cavity
Rare, late
Usually nodal
Rare extranodal; spreads to lung, spleen and liver
Histopathology
Epidermotropism All stages show marked epidermotropism and it usually follows a pagetoid or linear
pattern
Less pronounced, usually present in early lesions
Spongiosis Usually seen, sometimes
prominent with spongiotic vesicles
Rare
Necrotic keratinocytes Quite common Rare
Pautrier
microabscess
Common, with large
intraepidermal aggregates of atypical lymphocytes
Less common and scattered microaggregates of atypical lymphocytes
Depth of infiltrate Nodular or diffuse infiltrate extending to deep dermis or subcutis Superficial dermal infiltrate
Adnexae Usually involved (lymphoepithelioid pattern) Rarely affected, seen in syringotropic and folliculotropic variants
Angiocentricity and angioinvasion Relatively common Very rare
Immunophenotyping CD2–, CD4–, CD5–, CD45RO–
CD3+, CD7+, CD8+, CD45RA+
βF-1+, TIA-1+, perforin+, granzyme-B+ commonly positive
High Ki-67
CD4±, CD7–, CD45RA±
CD2+, CD3+, CD5+, CD8+, CD45RO+
TIA-1±, perforin±, granzyme-B± uncommon
Treatment
Conventional
therapy (skin-
directed treatment/low-dose methotrexate)
Ineffective Usually first line of treatment
Multiagent chemotherapy Usually required, though not effective
Allogenic hematopoietic stem
cell transplantation
Rarely needed

βF-1: Beta-factor-1, TIA-1: T-cell intracellular antigen-1

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Conflicts of interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

References

  1. , , , , , . The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133:1703-14.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , , , , . Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol. 1999;155:483-92.
    [CrossRef] [Google Scholar]
  3. , , , , , , et al. Aggressive epidermotropic cutaneous CD8+ lymphoma: A cutaneous lymphoma with distinct clinical and pathological features, Report of an EORTC cutaneous lymphoma task force workshop. Histopathology. 2015;67:425-41.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , , et al. Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: Reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas. Mod Pathol. 2017;30:761-72.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. A case of Ketron-Goodman disease. Case Rep Dermatol. 2009;1:39-43.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , , . Cutaneous CD8+ cytotoxic T-cell lymphoma infiltrates: Clinicopathological correlation and outcome of 35 cases. Oncol Ther. 2016;4:199-210.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , . Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: Proposed diagnostic criteria and therapeutic evaluation. J Am Acad Dermatol. 2012;67:748-59.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , , , , et al. Fatal cytotoxic cutaneous lymphoma presenting as ulcerative psoriasis. Arch Dermatol. 2009;145:801-8.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , , . Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma: Long-term remission after brentuximab vedotin. Int J Dermatol. 2017;56:1448-50.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
2,665

PDF downloads
2,108
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections