mycosis fungoides

Definition: Mycosis fungoides (also known as Alibert-Bazin syndrome or granuloma fungoides), is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time.

Mycosis fungoides is the most common type of ’Cutaneous T-cell Lymphoma’ (CTCL). MF has architectural effacement and pleomorphic cerebriform lymphocytes.

Images

 Mycosis fungoides.

• https://twitter.com/JMGardnerMD/status/877468345808957440
• https://twitter.com/BenjaminAwood/status/877055519936045056

 Mycosis fungoides. The cerebriform nuclear morphology is highlighted by CD3.

• https://twitter.com/KyleBradleyMD/status/877192144418738178

Digital cases

 UI:918 : Mycosis fungoides.
 JRC:10716 : Mycosis fungoides.

Epdiemiology

Approximately 1000 new cases of mycosis fungoides occur per year in the USA (ie, 0.36 cases per 100,000 population).

An analysis of 20-year trends reporting on incidence and associated mortality of those with mycosis fungoides shows a decline in the mortality rate in the United States, perhaps related to an increased recognition and earlier diagnosis of the disease.

The overall mortality rate is 0.064 per 100,000 persons.

It is rare for the disease to appear before age 20, and it appears to be noticeably more common in males than females, especially over the age of 50, where the incidence of the disease (the risk per person in the population) does increase. The average age of onset is between 45 and 55 years of age for patients with patch and plaque disease only, but is over 60 for patients who present with tumours, erythroderma (red skin) or a leukemic form (the Sézary syndrome).

Pathopghysiology

Mycosis fungoides is a malignant lymphoma characterized by the expansion of a clone of CD4+ (or helper) memory T cells (CD45RO+) that normally patrol and home to the skin.

The malignant clone frequently lacks normal T-cell antigens such as CD2, CD5, or CD7. The normal and malignant cutaneous T cell homes to skin by virtue of interactions with dermal capillary endothelial cells.

Cutaneous T cells express cutaneous lymphocyte antigen (CLA), an adhesion molecule that mediates tethering of the T lymphocyte to endothelial cells in cutaneous postcapillary venules via its interaction with E-selectin.

Further promoting the proclivity of the cutaneous T cell to home in to the skin is the release by keratinocytes of cytokines, which infuse the dermis, coat the luminal surface of the dermal endothelial cells, and upregulate the adhesion molecules in the dermal capillary endothelial lumen, which react to CCR4 found on cutaneous T cells.

Extravasating into the dermis, the cells show an affinity for the epidermis, clustering around Langerhans cells as seen microscopically as Pautrier microabscesses.

However, the malignant cells that adhere to the skin retain the ability to exit the skin via afferent lymphatics. They travel to lymph nodes and then through efferent lymphatics back to the blood to join the circulating population of CLA-positive T cells.

Then, mycosis fungoides is fundamentally a systemic disease, even when the disease appears to be in an early stage and clinically limited to the skin.

Variants

 folliculotropic mycosis fungoides (17721200)

Cytogenetics

Chromosome abnormalities, mostly complex karyotypes, are seen in about 50% of patients with MF/SS, and there have only been a few instances of recurrent rearrangements.

 47% of abnormal karyotype by SKY/FISH (16382449)

• chromosome 10
• chromosome 6 (deletion)
• chromosome 3
• chromosome 7
• chromosome 9
• chromosome 17
• chromosome 19
• chromosome 1
• chromosome 12
• chromosome 8
• chromosome 11
• chromosome 13 (deletion)

 recurrent breakpoints

• 1p32-36 (16382449)
• 6q22-25 (16382449)
• 17p11.2-13 (16382449)
• 10q23-26 (16382449)
• 19p13.3(16382449)

 pseudodicentric translocation between the short arms of chromosomes 8 - dic(17;8)(p11.2;p11.2) (16382449)

CGH

 gains

• 1p36-pter gain
• 7 gain
• 9q34-qter gain
• 17q24-qter gain
• 19 gain

 losses

• 2q36-qter loss
• 9p21 loss
• 17p loss

LOH (17895757)

Prognosis

The mortality rate widely varies depending on the stage of disease at diagnosis.

Late-stage mycosis fungoides or Sézary syndrome is associated with declining immunocompetence. Death most often results from systemic infection, especially with Staphylococcus aureus, Pseudomonas aeruginosa, and other organisms.

Secondary malignancies, such as higher-grade non-Hodgkin lymphoma, Hodgkin disease, colon cancer, and cardiopulmonary complications (eg, high output failure, comorbid cardiopulmonary disease) also contribute to mortality.

Differential diagnosis

• The major differential diagnosis for a primary cutaneous T-cell lymphoproliferative disorder with CD30 (Ki-1) positivity includes primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, pagetoid reticulosis and transformed mycosis fungoides (MF).
• CD30 expression is not restricted to transformed MF but higher levels of dermal CD30 expression and, even more so, dermal Ki-67 levels are independent adverse prognostic indicators. (19898220)

 pseudo-mycosis fungoides ( pseudo-MF )

• anti-TNFalpha treatment / TNF inhibitors

Links

 Wikipedia
 e-medecine

See also

 Tumors

• Lymphomas
• cutaneous tumors
  • cutaneous T-cell lymphoma (CTCL)
    • mycosis fungoides

References

 CD30 Expression and Proliferative Fraction in Nontransformed Mycosis Fungoides. Edinger JT, Clark BZ, Pucevich BE, Geskin LJ, Swerdlow SH. Am J Surg Pathol. 2009 Oct 23. PMID: 19898220

 Katona TM, O’malley DP, Cheng L, Hiatt KM, Wang M, Anagnostou JJ Jr, Billings SD, Smoller BR. Loss of Heterozygosity Analysis Identifies Genetic Abnormalities in Mycosis Fungoides and Specific Loci Associated With Disease Progression. Am J Surg Pathol. 2007 Oct;31(10):1552-1556. PMID: 17895757

 Batista DA, Vonderheid EC, Hawkins A, Morsberger L, Long P, Murphy KM, Griffin CA. Multicolor fluorescence in situ hybridization (SKY) in mycosis fungoides and Sezary syndrome: search for recurrent chromosome abnormalities. Genes Chromosomes Cancer. 2006 Apr;45(4):383-91. PMID: 16382449

 Prochazkova M, Chevret E, Mainhaguiet G, Sobotka J, Vergier B, Belaud-Rotureau MA, Beylot-Barry M, Merlio JP. Common chromosomal abnormalities in mycosis fungoides transformation. Genes Chromosomes Cancer. 2007 Jun 21; PMID: 17584911

 Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med. 2004 May 6;350(19):1978-88. PMID: 15128898