Calderm 2017 NorCal Conference

Jiminy Cricket & Appropriate Use in Dermatopathology

Maxwell A. Fung, MD Professor of Clinical Dermatology & Pathology University of California, Davis Sacramento, California

No relevant financial relationships “Audience response (ARS)” a) Do you read your own dermpath? b) Read path for other providers? c) Mostly read path reports? +/- recut review d) More than one of the above? Objectives • Gain insight: WHEN to listen to the “little voice” in your head to “do the right thing,” improve patient care and stay out of trouble

• “Appropriate Use”: a concept to improve patient care, stay out of trouble, reduce cost, and get paid

Highly predictive dermpath “rule outs” • Epidermal inclusion cyst Ring CM, et al. Clinical simulators of cysts. J Am Acad Dermatol 2016; 75:1255-1257. • Lipoma • Skin tag • Pyogenic granuloma • Granuloma annulare 58/M “r/o cyst” left chest 58/M “r/o cyst” left chest 22/M “FINAL DIAGNOSIS: CYST, EXCISION” 22/M “FINAL DIAGNOSIS: CYST, EXCISION”

Post-op √ “Wound is closed, no redness”

22/M “FINAL DIAGNOSIS: CYST, EXCISION”

What would you do next? a) Accept diagnosis b) Additional excision c) Call pathologist d) Review pathology/2nd opinion

“FINAL DIAGNOSIS: CYST, EXCISION” What is the “official” disease of California? Coccidioidomycosis (California disease, Valley fever, San Joaquin Valley fever, desert rheumatism) H&E • Coccidioides immitis

• Thick walled spherule PAS containing endospores 10-80 mm “FINAL DIAGNOSIS: CYST, EXCISION” Annular plaques in a woman from SoCal

• 81/WF from The OC • 4 year history annular erythematous dermal plaques • Started on left upper arm • Clinical diagnosis: GA (multiple derms) 81 yr old woman R/O GA right flank 81 yr old woman, R/O GA 81 yr old woman, R/O GA 81 yr old woman, R/O GA 81 yr old woman, R/O GA 81 yr old woman, R/O GA What is your diagnosis?

a) Actinic granuloma b) Granuloma annulare c) Interstitial granulomatous dermatitis d) Other 81 yr old woman, R/O GA GA-like BT leprosy

Zhu TH, Kamangar F, Silverstein M, Fung MA. Borderline tuberculoid leprosy masquerading as granuloma annulare: a clinical and histological pitfall. Am J Dermatopathol 2017;39:296-299.

Fite

Images courtesy Colin Bodet, Keyence Corp. DDx for perineural plasma cells • leprosy • perineural granulomas, nearly always • lupus erythematosus • morphea

• cutaneous plasmacytosis (#dermpathJC) • perineural invasion

Leprosy, borderline tuberculoid (BT)

79/M hx BCCsMTS -ass’d cystic sebaceous CA Growing 1 cm lesion R upper chest R/O BCC ? ? Diagnosis? a) Keratoacanthoma b) Sebaceous adenoma c) Combo neoplasm (“seboacanthoma”) What is a “most commonly missed” diagnosis? (Trick question) Sebaceous adenoma Sebaceoma Sebaceous carcinoma Muir-Torre Syndrome OMIM #158320 • Subset of Lynch syndrome (HNPCC) • Multiple sebaceous neoplasms +/- KA • Visceral malignancy: colon > GU, other • Germline mutation affecting DNA mismatch repair proteins (”housekeeping”) • + family history Hereditary Non-polyposis Colorectal Cancer (Lynch Syndrome I-II, OMIM #120435 etc) • Amsterdam Criteria – ≥ 3 relatives with colorectal CA (CRC); exclude familial adenomatous polyposis (FAP) – ≥ 2 affected generations – 1 or more diagnosis of HNPCC-related CA age < 50

• Bethesda Criteria (revised, 2004) – Colorectal CA, age <50 – Synchronous or metachronous CRC or HNPCC-related CA, any age – CRC w MSI-H histology, age < 60 yrs – ≥ 1 1st degree relative with CRC + HNPCC-related CA, age < 50 – ≥ 2 1st or 2nd degree relative with CRC + HNPCC-related CA Umar A, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and Microsatellite Instability J Natl Cancer Inst 2004;96:261-268

The 1st description of a family with Lynch syndrome is credited to? a) Moritz Kaposi b) Henry Lynch c) Peter Lynch d) Alfred Warthin Next step(s)? a) Notify patient they might have MTS b) Obtain complete medical history c) Request or await ancillary test results d) Refer (primary MD, genetics) Which ancillary tests are appropriate now? a) Reflex testing: MSH-2/MSH-6/MLH-1/PMS-2 b) Reflex testing: MSI (microsatellite instability) c) MSH-2 mutation analysis d) Offer testing if clinically indicated e) No action Dermpath’s role? a) Obtain screening IHC (x4) for MTS b) Offer screening upon request by provider c) Call the clinician to decide whether to order IHC (x2-4) screening What recommendation is appropriate?

“Sebaceous neoplasms may form part of the spectrum of Muir-Torre syndrome (subset of Lynch syndrome). Immunohistochemical screening for evidence of a DNA mismatch repair protein may be performed upon request.”

Eisen DB, Michael D. Sebaceous lesions and their associated syndromes. Part II. J Am Acad Dermatol 2009;61:573-78. 2016 ASDP 53rd Annual Meeting responders say . . . What recommendation is appropriate? “Sebaceous neoplasms, especially if multiple, extrafacial and/or before age 50, may form part of the spectrum of Muir-Torre syndrome (subset of Lynch syndrome). Immunohistochemical screening for evidence of a DNA mismatch repair protein may be performed upon request.”

Abbas O, Mahalingam M. Cutaneous sebaceous as markers of Muir-Torre syndrome: a diagnostic algorithm. J Cutan Pathol 2009;36:613-19. ?

MLH-1 MSH-2 MSH-6 PMS-2 ?

MLH-1 MSH-2 MSH-6 64/M 1 cm flesh colored papule on left pinky

Lesion present x 1 years, slowly growing, asymptomatic 1 cm flesh colored firm papule R/O acquired digital fibrokeratoma DIAGNOSIS: “CONSISTENT WITH GRANULOMA ANNULARE” 64/M 1 cm flesh colored papule on left pinky 64/M 1 cm flesh colored papule on left pinky 64/M 1 cm flesh colored papule on left pinky

acquired digital fibrokeratoma “R/O scleroderma/morphea” • 14/F • Thick, firm plaque with no epidermal change • Biopsy from R lateral thigh

Courtesy Smita Awasthi, MD “R/O scleroderma/morphea” DIAGNOSIS: “SPARSE DERMAL INFLAMMATION WITH SUPERFICIAL ADIPOCYTES AND LIMITED EVIDENCE OF SCLEROSIS, SEE NOTE. Note: The appearances do not exclude but are not classic for morphea. Specifically, the presence of scattered adipocytes within the reticular dermis is not typical of morphea. The EVG stain demonstrates preserved, variably thickened/clumped elastic fibers in the reticular dermis, against scar. The clinical presentation does not seem to support the histologic consideration of focal dermal hypoplasia (Goltz syndrome) or an elastoma type of linear connective tissue nevus.

The case was reviewed with Dr. P, the submitting dermatology resident physician, who kindly shared clinical images of this case.

Deeper sections were obtained. I also shared this case with my colleague, Dr. K. What would you do? • A) Clinical follow up • B) Consult colleague(s) • C) Refer to the university

Courtesy Smita Awasthi, MD “R/O scleroderma/ morphea” “R/O scleroderma/ morphea” Diagnosis?

a) Connective tissue nevus b) Goltz syndrome c) Morphea d) Stiff skin syndrome Stiff skin syndrome • Congenital fascial dystrophy

• Fibrillin-1 mutations (TB4 domain)

• Localized > generalized

• Usually pelvic +/- shoulder girdle Esterly NB, McKusick VA. • Hypertrichosis Stiff skin syndrome. Pediatrics • No underlying tissue overgrowth 1971;47:360.

• Contracture-like joint, postural, thoracic, ocular restriction Stiff skin syndrome • Woven or lattice-like pattern of collagen + entrapped fat

• No inflammation

• Adnexa spared

• Interstitial mucin variable

• Elastin preserved

Stiff skin syndrome Stiff skin syndrome Stiff skin syndrome Stiff skin syndrome

• Clinically may resemble morphea or Becker’s nevus

• Histologically may resemble normal skin, scleredema, morphea, Goltz, superficial lipoma

Melanoma • 18 year old Asian • New mole x 1 year • 3 mm raised mole with inflamed base. R/O Neoplasm of uncertain behavior

• Diagnosis: melanoma, superficial spreading type, 0.95 mm in thickness, Clark’s IV, no LVI or mitoses, T1aNx Melanoma

• 18 year old Asian • New mole x 1 year, left leg above knee • 3 mm raised mole with inflamed base. R/O Neoplasm of uncertain behavior

• Diagnosis: melanoma, superficial spreading type, 0.95 mm in thickness, Clark’s IV, no LVI or mitoses, T1aNx Melanoma

• Uncommon below age 20 • Non-acral melanoma uncommon in Asians • Dermatopathologist(s) review

67/M “nevus R/O atypia” left calf 67/M “nevus R/O atypia” left calf 67/M “nevus R/O atypia” left calf 67/M “nevus R/O atypia” left calf 67/M “nevus R/O atypia” left calf Melanoma, pT1a What % of melanomas require immunohistochemical (IHC) “confirmation”?

“MUST HAVE: MELANOMA IMMUNOHISTOCHEMICAL PANEL (HMB-45, Melan-A): This must be included when upgrading a clinical dysplastic nevus to a more serious melanocytic? lesion.” What % of melanomas require immunohistochemical (IHC) “confirmation”? “MUST HAVE: MELANOMA IMMUNOHISTOCHEMICAL PANEL (HMB-45, Melan-A): This is often employed to support a diagnosis of Spitz nevus and should always be present in? a diagnosis of spitzoid melanoma.” What are appropriate indications for IHC for melanoma? a) All melanomas b) Amelanotic c) No in situ component d) Lineage/differentiation uncertain

What % of melanomas require immunohistochemical (IHC) “confirmation”? a) <10% b) 25% c) 50% d) 75% e) >90% (melanoma IHC panel) What % of biopsies for dermatitis requires a stain to rule out tinea? a) <10% b) 25% c) 50% d) 75% e) >90% What are appropriate indications for a PAS stain? a) All biopsies for inflammatory diseases b) Selected inflammatory features c) Selected cases d) All nail clippings for onychomycosis e) Nail clippings only if pathogens not seen on H&E What are appropriate indications for a PAS stain?

• 57% cases detected on H&E alone • PAS is justified

Al-Amiri A, et al. The Periodic-acid Schiff stain in diagnosing tinea: should it be used routinely in inflammatory skin diseases? J Cutan Pathol 2003;30:611-5. PASD Can you see me now? H&E What are appropriate indications for a PAS stain?

• PAS is justified • May be deferred until after H&E viewed

Wang MZ, et al. Correlation between histopathologic features and likelihood of identifying superficial dermatophytosis with periodic acid Schiff- diastase staining: a cohort study. J Cutan Pathol 2017;44:152-157. What % of nail clippings require a stain to rule out tinea? a) <10% b) 25% c) 50% d) 75% e) >90% Summary • “Appropriate Use”: a perhaps onerous but necessary concept to improve patient care, stay out of trouble, and get paid • Muir-Torre screening? • Melanoma markers? • PAS stain?

Summary • Gain insight into WHEN to listen to the “little voice” in your head to “do the right thing,” improve patient care and stay out of trouble – Pursue clinical-pathologic “disconnects” – Communicate with provider / pathologist – Obtain additional input