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Submission Instructions for RNA in situ hybridization (RISH) studies

For psoriasis versus dermatitis and diagnosis of lupus and dermatomyositis

Case Submission Instructions

Testing of prior biopsies:

  • If a biopsy is available at Yale Dermatopathology, call or email Yale Dermpath
    to request RISH testing (contact info below)
  • If a biopsy is available at another laboratory, request Yale Dermpath consult with
    RISH testing; please send outside H&E slides, tissue block(s) and report.

Testing of new biopsies:

  • Send specimen to Yale Dermatopathology by trackable mail FedEx, request "RISH" on the requisition.

Clinical history:

  • For optimal interpretation of all cases, please include brief relevant history.
    • Clinical diagnosis or differential diagnosis
    • Biologic or other systemic therapies at the time of the biopsy
    • Response patterns to prior therapies, e.g. nonresponse, worsening, morphology change)

Shipping address, please use FedEx:

Dr. Jennifer McNiff
Yale Dermatopathology
15 York Street LMP 5031
New Haven 06510

Frequently Asked Questions

Can I request this testing on a case that was previously signed out by Yale Dermatopathology?

Yes, please email or call (below) to request the testing. An addended report will be issued.

Can older cases be tested?

Yes, archival blocks up to 10 years old have been successfully evaluated

Can this testing exclude cutaneous T cell lymphoma?

No, appropriate additional workup and molecular studies for T cell clonality should be considered on a case-by-case basis

How is RISH testing billed?

Patient insurance will be billed for a panel of 4 biomarkers (IL17A, NOS2, IL13, IFNG) or single marker (ISG15) by in situ hybridization, typically covered by insurance

Background

Marker panel for psoriasis and dermatitis

Name Description
IL17A Biomarker of psoriasis-like immunology

Generally negative in eczematous diseases

Our experience to date suggests the presence of this marker correlates with responsiveness to molecularly targeted psoriasis therapies against IL-23, IL-17, and others
NOS2 Biomarker of psoriasis-like immunology

Generally negative in eczematous diseases
IL13 Biomarker of atopic/eczematous dermatitis and immunologically related disorders

Our experience to date suggests the presence of this marker correlates with responsiveness to molecularly targeted dermatitis therapies against IL-13 and IL-4Ra
IFNG (Interferon gamma) Generally positive in psoriasis cases

When significant staining is seen in cases of eczematous/atopic dermatitis, in our experience,
- these patients may respond sub-optimally to IL-13 and IL-4Ra inhibitors.
- consider allergic contact dermatitis or superimposed allergic contact dermatitis.

Marker for interferon-high connective tissue diseases (lupus erythematosus and dermatomyositis)

Name Description
ISG15 and IFI6 Biomarkers of elevated type I interferon signatures in the skin – increased in cutaneous lupus, systemic lupus, dermatomyositis, and other immunologically related disorders.

Suggestive of strong response to type I interferon-targeted therapies like type I interferon receptor (IFNAR) antagonists or TYK2 inhibitors.

Disclaimer

This test is not FDA approved. This testing does not have the ability to exclude the possibility of cutaneous T cell lymphoma. This testing was developed by the Yale Dermatopathology laboratory to detect mRNA of key cytokines and biomarkers in inflammatory skin disease. The information below is based on our collective experience to date with this approach. The relevance of staining to any individual case requires clinical-pathologic correlation.

Molecular Instruments partnered with Yale on the development of these tests.

References

  1. Wang A, Fogel AL, Murphy MJ, Panse G, McGeary MK, McNiff JM, Bosenberg M, Vesely MD, Cohen JM, Ko CJ, King BA, Damsky W. Cytokine in situ hybridization permits individualized molecular phenotyping in biopsies of psoriasis and atopic dermatitis. JID lnnov. 2021; 1:1000021.
  2. Singh K, Valido K, Swallow M, Okifo KO, Wang A, Cohen JM, Damsky W. Baseline skin cytokine profiles determined by RNA in situ hybridization correlate with response to dupilumab in patients with eczematous dermatitis. J Am Acad Dermatol. 2023; 88: 1094.
  3. Chen JS, Murphy MJ, Singh K, Wang A, Chow RD, Kim SR, Cohen JM, Ko CJ, Damsky W. IL17A mRNA staining distinguishes palmoplantar psoriasis from hyperkeratotic palmoplantar eczema in diagnostic skin biopsies. JID lnnov. 2023; 3: 100189.