#dermpathJC February 2019 summary

#dermpathJC February 2019:

Thursday, February 21, 9pm EST

Article discussed: Solid carcinoma is a variant of microcystic adnexal carcinoma: A 14‐case series

Authors: Yosmar Carolina, Perez-Gonzalez, Ramon Bosch-Princep, Maria-Teresa-Fernandez-Figueras, Arno Rutten.

Temporary open access at: https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13351

Summary prepared by Abha Soni, DO, MPH (@AsoniDO)

 

Journal Club summary:

This month’s journal club discussed a rare skin neoplasm that closely resembles the solid areas of microcystic adnexal carcinoma (MAC). The article was a good review of the histologic, and immunohistochemical features of this entity.

In case you missed our discussion this week, the summary is provided below:

Only 16 cases of sold carcinoma have been previously published. This paper presents 14 additional cases of sold carcinoma and reviews their morphologic and immunohistochemical features.

Histology:

  • Groups of neoplastic epithelial cells with small monomorphous nuclei.
  • Cells form small solid aggregates that vary in size and shape and fill the dermis and extend through adipose tissue.
  • Nuclear atypia and mitotic figures are rare.

Screen Shot 2019-03-13 at 12.46.23 PM

  • Perineural invasion and infiltrative borders are identified.

screen-shot-2019-03-13-at-12.46.28-pm.png

  • Small cornifying cysts/follicular derived cysts can be found in the upper part of the neoplasm.

Screen Shot 2019-03-13 at 12.47.11 PM

  • Some nests show clear cell features without a prominent basal cell layer.
  • These cells showed abundant cytoplasm, single nucleolus, and their nuclei tended to be located near the apices of the cells

Screen Shot 2019-03-13 at 12.47.02 PM

Immunohistochemistry:

  • Neoplastic cells exhibit high-molecular weight keratin (cytokeratin 5/6), broad specterum keratin (AE1/AE3), and p63, with focal CEA immunoreactivity.
  • Negativity for ER, PR, BerEP4, EMA, Cytokeratin 7, Cytokeratin 20, Cytokeratin 18, SMA, S-100, CD15, and GCDFP-15.
  • p53 is associated with uncontrolled proliferation and interpreted as an indicator of aggressive behavior and was only expressed in less than 5% of cells in the tested cases.
  • p63 shows a homogenous expression than in classic MAC.
  • CK19 is positive in some small ductal structures within the neoplasm
  • PHLDA-1 was negative in the cases studied (unlike previous papers). It appeared to stain part of the epithelium of cystic structures.

Screen Shot 2019-03-13 at 12.47.19 PM

Discussion:

  • Clinicians must determine whether this is a unique clinicopathologic entity or if it belongs to the spectrum of MAC.
  • Differential diagnosis includes:
    • Clear-cell dermal duct tumor
      • Differentiating features: Absence of cystic structures on the superficial aspect of the neoplasm in dermal duct tumor, and absence of infiltrative pattern without perineural invasion.
    • Sclerosing basal cell carcinoma
      • Differentiating features: BerEP4 would be positive in both sclerosing and clear cell BCC and negative in solid carcinoma/solid variant of MAC.
    • Desmoplastic trichoepithelioma
      • Tumor cells are basaloid and show presence of rims of collagen bundles around the neoplastic cell cords as well as absence of perineural involvement. Additionally, are confined to the upper/mid dermis.
    • Solid variant of MAC vs classic MAC:
      • Classic MAC clinically presents in locations such as lips and face and rarely the scalp. Whereas, the current series, scalp location seems to be more associated with the solid variant of MAC.
    • Solid carcinoma should be referred to as the solid variant of MAC, histopathologic features of this entity belong to the MAC morphologic spectrum.


See you all next month
! 😉

#dermpathJC January 2019 summary

#dermpathjc January 2019:

Thursday, January 24, 9pm EST

Article discussed: Pigmented Lesions of the Nail Unit

Authors: Nevares-Pomales O, Sarriera-Lazaro C, Barrera-Llaurador J, Santiago-Vazquez M, Lugo-Fagundo N, Sanchez JE, Sanchez JL.

Temporary open access at: https://journals.lww.com/amjdermatopathology/Abstract/2018/11000/Pigmented_Lesions_of_the_Nail_Unit.1.aspx

Summary prepared by Patrick Rush, DO (@DrPatrickRush)

 

Journal Club summary:

This month’s journal club article discussed a topic that gives many of us much consternation, pigmented lesions of the nail unit. The article was a good overall review in many regards; there was discussion (with images) of the clinical features of melanocytic lesions and the concerning signs, as well as a review of the epidemiology, histology, and molecular findings. The learning objectives for the article were very well laid out, and there are accompanying CME questions for obtaining AMA PRA Category 1 credits.

It was a lively discussion, and those active in the discussion overall agreed with the author’s summary and findings.

There were a few take home points from the paper and subsequent discussion, which touched on all aspects:

Embryology:

  • Proximal nail matrix = predominantly dormant melanocytes
  • Distal nail matrix = active and dormant melanocytes (more likely for a melanocytic lesion to arise within this zone)

Epidemiology:

  • Melanocytic macule more common in adults
  • Nevi more common in children

Clinical:

  • Longitudinal melanonychia not always due to a melanocytic lesion (Fungus, drugs, trauma, infection, etc can be causative)
  • Amelanotic subungual melanoma has been reported at rates between 15-50% (while they only comprise 2-8% of melanomas at other sites)

Sampling:

  • Many seem to groan with nail clippings to evaluate for a melanocytic lesion
  • If clippings are sent, if negative they will usually be emblazoned with a caveat in an comment

Histology:

  • Most peoples malignant lesions have been composed of melanoma in situ with invasive melanoma making up the minority.

Immunohistochemistry:

  • SOX10 not as useful in the nail unit as in other parts of the body
  • Mart-1 / Melan A are preferred, and felt to work better
  • Some also order a Fontana Mason in addition

Molecular:

  • Subungual melanoma more commonly harbor KIT mutations
  • Predictions through immunohistochemistry has thus failed to be predictive of molecular aberrations
  • Gold standard for interrogation of KIT mutations remains molecular analysis

Some Highlights from the Evening:

jan1

Jan2

jan3

jan4-e1550170296656.png

Top: nail plate chromomycosis

Bottom: nail plate onychomycosis

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The conversations were great again, with a nice mix of Dermatologists and Pathologists from all over the world. Hope to see you again next time!

 

#dermpathJC December 2018 summary

Thursday, December 27, 9pm EST

Article discussed: Selected Pseudoneoplastic Lesions of the Skin

Author: Mark R. Wick and James W. Patterson

Open access at: http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165-134.3.369

Summary prepared by Jisun Cha, MD (@sunpungi)

 

Journal Club Summary:

Hair follicle “bulges” (der Wulst) are commonly seen in dermpath sections. How they differentiate from BCC – usually vertically oriented, surrounded by normal dermis, prominent basement membrane, no mitoses, no atypia and lack of myxoid stroma. Normal structure of hair follicles in the central facial skin.

1

PEH (Pseudoepitheliomatous hyperplasia) can be associated with many different types of lesions. Here is a nice summary table from @SGottesmanMD.

82

Most dermpathJC participants agree that verrucous carcinoma can be quite impossible to distinguish from pseudoepitheliomatous hyperplasia in certain scenarios. This is where additional clinical information may be helpful.

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Pseuodsarcomatous fibroepithelial polyp – fatty core which shows pleomorphic lipoblast-like cells which have similarity to pleomorphic lipomas and some deep soft tissue sarcomas (liposracoma). These changes are thought to be of a degenerative nature. They are very rare as most dermpathJC participants have never seen such changes in fibroepithelial polyps. @JMGardnerMD is wondering if some of these are in the pleomorphic fibroma/lipoma spectrum, and would be cool to do RB1 on a specimen like this. Additional reading about loss of retinblastoma in pleomorphic fibroma: https://www.ncbi.nlm.nih.gov/m/pubmed/28543636/

3Acroangiodermatitis of Mali aka dermatitis hemostatica aka Bluefarb-Stewart syndrome aka pseudo-Kaposi sarcoma. Here’s another useful table from @SGottesmanMD.

7

4

Reactive angioendotheliomatosis (term used in several different ways and is still confusing to most participants)

  • Reactive vascular proliferation
  • Reactive histiocytes proliferation filling dilated vessels

5

And last but not least, basaloid, follicular and sebaceous induction over a dermatofibroma. Photos by , and

9

10

11

Hope you have a happy New Year and we will see you January 24th, 2019 at 9pm EST for another exciting dermpath journal club.

 

Kind regards,

Silvija Gottesman, MD

#dermpathJC November 2018 summary:

Thursday, November 29, 9pm EST

Book discussed: WHO Classification of Skin Tumours

Special Guests: Dr Richard A. Scolyer (@ProfRScolyerMIA) and Dr Rajendra Sing (@mydermpath)

Summary prepared by Abha Soni, DO, MPH (@AsoniDO)

 

Journal Club Summary:

Topics Discussed:

 Variants of cutaneous SCC:

    1. Squamous cell carcinoma (NOS)
    2. Keratoacanthoma*
    3. Verrucous SCC*
    4. Acantholytic SCC
    5. Adenosquamous SCC
    6. Spindle cell SCC
    7. Rare variants (Lymphoepithelial-like SCC, Pseudovascular SCC, and SCC with sarcomatoid differentiation)

*These low-grade variants can be locally destructive but have little potential to metastasize

2.jpg

Basal Cell Carcinoma:

  1. Lower Risk: Superficial, nodular, pigmented, infundibulocystic, Fibroepithelioma of Pinkus
    • Fibroedpitheloma of Pinkus, aka Pinkus tumor renamed as fibroepithelial basal cell carcinoma
  2. Higher Risk: Micronodular, infiltrating, morpheaform/sclerosing, basosquamous carcinoma, BCC with sarcomatoid differentiation
    • Micronodular: irregular, infiltrative deep/peripheral edges. Defined as >50 small nodules (<0.15 mm in diameter)
    • Infiltrating: Small irregular/jagged nests, at least 5-8 cells thick at least
      1. In contrast, Dr. Singh explained that morpheaform can be less than 5 cells thick. “In short, morpheaform tends to have smaller basaloid nests. But to stress again many consider them as same of overlapping features.”
      2. Others commented that in the morpheaform subtype they also look for dense fibrous/keloid-like collagen fibers

Basosquamous: Zones contain cells with intermediate features between the two. The basaloid component stains positive for BerEP4 and the squamous areas express MUC1 (EMA)

Melanocytic Tumors:3

  • This new approach to melanoma classification was appreciated by many in the Dermpath JC twitter community as there is a higher emphasis on the chronicity of sun damage and how it impacts certain pathways in melanoma progression.
  • Two main pathways CDKN2A pathway and the MAPK pathway were discussed.

 

Dysplastic Nevi:

Low Grade: Moderate cytologic and architectural atypia

High Grade: Severe cytologic and architectural atypia

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BAPOMA: Combined nevus with a benign nevic component and almost a spitzoid component. Some spitz like areas show multinucleation with an admixed infiltrate.

BAP1 lost especially present in the larger cells. BRAF mutations mostly also seen.

 

New Entities:

  1. Endocrine mucin producing sweat gland carcinoma
    • Low-grade neuroendocrine neoplasm
    • Predilection for eyelid and periorbital skin. However, occurrence in an extrafacial location has also been reported.
    • Precursor of mucinous carcinoma
    • Older individuals (i.e. in the sixth and seventh decades of life)
    • Positive for CK7, CK8, CK18, AE1/AE3, CAM5.2, EMA, GCDFP15, WT1, ER and PR. Intensity for chromogranin and synaptophysin varies. Ki-67 is low.
  2. Squamoid eccrine ductal carcinoma
    • Present as large nodules and plaques in the head and neck area.
    • Positive for cytokeratin and ductal differentiation can be confirmed by MUC1 and CEA.
  3. Secretory carcinoma of the skin
    • Axillary location.
    • Rare sites include the face (including the lips), trunk, and limbs.
  4. Signet ring cell/histiocytoid carcinoma
    • Males>females
    • Predilection for eyelids, but identical neoplasms have been reported in the axilla.
  5. Hematolymphoid tumors
    1. CD30 lymphoproliferative disorders
      • Types A-C morphologic criteria remain the same.
      • Type D: shows epidermotropic infiltrates of CD8+ and CD30+ atypical cells and mimics primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.
      • Type E: characterized by angiocentric and destructive infiltrates, predominantly medium sized atypical CD30+ lymphocytes with extensive dermal necrosis and ulceration.
    2. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder
      • Solitary skin lesion, and no evidence of the patches or plaques.
      • Ulcer/papules show spontaneous regression.
      • Expression of PD-1(follicular T-cell marker), monoclonality of T-cell receptor (60%).
      • Similar phenotype has been observed in patients with multiple lesions. This is still an understudied area and it is important to recognize for therapeutic options and to determine prognosis.

Soft tissue tumors:

  1. New Entities
    • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma
      1. Spindled to epithelioid, rarely metastasizing neoplasm
      2. Mimics myotid tumor or epithelioid sarcoma
      3. SEPINE1-FOSB fusion
      4. Male predominance
      5. Lower extremities > upper extremities or trunk
      6. FOSB consistently positive
    • Cutaneous leiomyosarcoma
      1. Prognosis of these tumors is superb, no metastases
      2. Grading is not of prognostic value
    • Angiosarcoma
    • Majority associated with radiation or preexisting lymphedema are associated with MYC gene amplification and co-amplification of FLT-4.
      1. This may be helpful in cases where MYC amplification is not seen.

 

 Special thanks to Dr. Singh (@mydermpath) for putting the presentation together and to the @DermpathJC twitter community for another successful discussion.

 The detailed slides/summary and accompanying virtual images can be accessed here:

 Pathpresenter.net

Login: pp@gmail.com

Password: welcomepp

Click on: My presentations

Click on DermpathJC

 Here are the corresponding diagnoses to the online virtual images: 

  1. Keratoacanthoma
  2. Verrucous carcinoma
  3. Micronodular basal cell carcinoma
  4. Morpheaform BCC
  5. Infiltrative bcc
  6. Bapoma
  7. Trichoblastic carcinoma
  8. Secretory carcinoma
  9. Endocrine mucin producing sweat gland carcinoma
  10. Signet ring/histicocytoid carcinoma
  11. Squamoid eccrine carcinoma
  12. CEA
  13. Adnexal adenocarcinoma NOS
  14. Leiyomyosarcoma
  15. Pseudomyogenic hemangioendothelioma
  16. Epithelioid histiocytoma
  17. Type E LYP
  18. Erdheim Chester Disease
  19. Conjunctival melanoma
  20. Conjunctival primary acquired melanosis
  21. Conjunctival nevus

 

Thanks to all who participated! See you in December! Save the date 12/27/2018, 9pmEST.

Kind regards,

Silvija Gottesman, MD

#dermpathJC October 2018 summary:

#dermpathjc October 2018:

Thursday, October 25, 9pm EST

Article discussed: Verruciform and Condyloma-like Squamous Proliferations in the Anogenital Region.

Author: May P. Chan from the Archives of Pathology and Laboratory Medicine

Free access at: http://www.archivesofpathology.org/doi/10.5858/arpa.2018-0039-RA

Summary prepared by Dr. Katy Veprauskas (@LinskeyKaty)

 

Journal Club Summary:

Background: Histologic distinction between condyloma acuminatum and various benign and malignant condyloma-like lesions in the anogenital area poses a common diagnostic challenge to pathologists across subspecialties.

Aim of study: To review the overlapping and distinguishing features of condyloma acuminatum and its mimics, and to clarify confusing terminology and diagnostic criteria for problematic entities.

Results: Correct diagnosis of condyloma acuminatum and condyloma-like lesions has important clinical implication and entails familiarization with their clinical presentations and histopathologic features. Contrary to historical belief, giant condyloma acuminatum and verrucous carcinoma should be considered distinct entities based on different pathogenetic pathways. Ancillary tools available for identifying and genotyping human papillomavirus can aid in diagnosis when histopathologic findings are inconclusive. Recognition of relatively rare entities such as bowenoid papulosis, epidermolytic acanthoma, and verruciform xanthoma would avoid overdiagnosis and unnecessary, overaggressive treatment.

Limitations: This was a literature review and did not present original data.

Twitter Journal Club Discussion Summary:

● Issue of vulvar SK (HPV and non-HPV related) was discussed; approaches include:

○ Consideration of age: younger patients generally more likely to be HPV+ and less likely to have SK in general

■ ASDP AUC used 25 yrs old as cutoff; SK very rare under that age

■ study of vulvar SK in women >50 yrs showed low incidence of HPV+, with 3/28 patients HPV+ (14%; vs other studies which showed closer to 70% in younger pts) (Reutter J, J Low Genit Tract Dis. 2014, https://www.ncbi.nlm.nih.gov/pubmed/24556611 )

○ Koilocytes helpful in diagnosing condy vs SK

○ Many participants favor a descriptive diagnosis and offer HPV testing in comment upon clinician request

○ Ki67 helpful for some; staining in upper layers of the epithelium more supportive of condy (Pirog et al AJSP 2000, Bai et al Hum Pathol 2003)

● HPV testing on low grade lesions:

○ Modalities: ISH appears most popular (though some use PCR), sendout labs used included ARUP and Mayo

○ Most do not order HPV testing routinely; will order upon clinician request

○ Important to note that there can be false positives and false negatives; some condy can be caused by high risk or HPV types other than 6/11, so condy that comes back as HPV low risk negative by ISH may be a false negative

○ HPV testing was reviewed in ASDP appropriate use committee (AUC):

https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13142 ; found HPV testing “rarely appropriate” in many scenarios, exception being pediatric cases with path suggestive of condy (HPV testing “usually appropriate” in these cases)

● LAST terminology was discussed: many participants incorporate LSIL and HSIL into diagnosis of HPV related lesions of the anogenital region

○ Some only use “condyloma” for papillomatous low grade squamous lesions in the vulva and reserve LSIL for lesions that appear flat, others use both terms (“condyloma (LSIL)”)

○ It was noted that the ISSVD (International Society for the Study of Vulvovaginal Disorders) published terminology in 2015 highlighting specific issues related to vulvar SIL in the LAST criteria; they noted that LSIL should be used in regards to “flat condyloma or HPV effect” and also emphasized that LAST does not refer to differentiated VIN, which is considered a separate, non-HPV related form of high grade VIN (https://www.ncbi.nlm.nih.gov/pubmed/26704327 )

● Diagnosis of bowenoid papulosis relies on clinical correlation; suggested approach by some participants would be to diagnose case as HSIL/VIN3 and add comment that it could be c/w bowenoid papulosis in the appropriate clinical setting

● Giant condy vs verrucous CA:

○ traditionally (and still in some texts) taught that both are HPV-related, but while giant condy is usually associated with HPV 6/11, verrucous CA not HPV-related in studies with cases defined by strict histopathologic criteria

○ Giant condy usually associated with other STDs, VC assoc w/ inflammatory conditions such as lichen sclerosus

Thanks to all who participated! See you in November!

#dermpathJC September 2018 summary:

#dermpathJC September 2018:

Thursday, September 27th, 9pm EST

Article discussed: Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Authors:  Claudia I. Vidal, Eric A. Armbrect, Aleodor A. Andea, Angela K. Bohlke,  Nneka I. Comfere, Sarah R. Hughes, Jinah Kim, Jessica A. Kozel, Jason B. Lee, Konstantinos Linos, Brandon R. Litzner, Tricia A. Missall, Roberto A. Novoa, Uma Sundram, Brian L. Swick, Maria Yadira Hurley, Murad Alam, Zsolt Argenyi, Lyn M. Duncan, Dirk M. Elston, Patrick O. Emanuel, Tammie Ferringer, Maxwell A. Fung, Gregory A. Hosler, Alexander J. Lazar, Lori Lowe, Jose A. Plaza, Victor G. Prieto, June K. Robinson, Andras Schaffer, Antonio Subtil, Wei‐Lien Wang

Temporary open access available at https://doi.org/10.1111/cup.13142

Summary author: Patrick Rush, DO (@DrPatrickRush)

Journal Club Summary:

The month’s journal club article reviewed the recently published work by the American Society of Dermatopathology on appropriate use. This article is the first of what seems like will be several works from the American Society of Dermatopathology (ASDP) with input from the American Academy of Dermatology (AAD) and the College of American Pathologists (CAP) on appropriate use criteria as it applies to the field of Dermatopathology; specifically the group addressed 211 clinical scenarios and 12 ancillary studies. This publication outlined the appropriateness (without comparison between tests or consideration of costs) of 12 ancillary tests.

The journal club was once again maintained a lively discussion with a good number of participants from all over, with over 30 participants tweeting over 200 times and leaving 762.563K impressions over the following week.

1

All together the active participants seemed to agree with the sentiments of a comment made by @MightyDermPath that the work was not very controversial, but that it was an important start.

2

It was a common comment that the article was very table heavy that made for some dense reading. However, the upside being it was very easy to go back and read through their thought process.

3

The AUC took the above systematic approach to stratifying their recommendations are rarely appropriate, uncertain, and usually appropriate. Raters were also allowed use an “OUT” options if they felt that consultation with the clinician was necessary to determine the appropriateness, and this occurred in only 9 clinical scenarios where >3 panel raters used the OUT option. Altogether they rated 211 clinical scenarios and a consensus was reached for 188 (89%) of them. The major issues to be addressed were separated into general groups: Lymphoproliferative, melanocytic, soft tissue, Muir-Torre syndrome mismatch repair IHC, Other (HPV, ISH, IHC).

Lymphoproliferative group:

B and T cell receptor rearrangement studies were addressed in this group.

4

Melanocytic group:

The use of FISH, CGH and qRT-PCR were addressed in this group.

5

Soft tissue group:

FISH testing for EWSR1 for clear cell sarcoma and t(17;22) in DFSP were discussed in this group.

6

Muir-Torre syndrome mismatch repair IHC:

The use of an IHC antibody panel for screening of Muir-Torre syndrome (a subset of Lynch) were discussed in this group.

7

Other (HPV, ISH, IHC):

The use of IHC or ISH in the evaluation of HPV association of different squamous lesions was evaluated in this group.

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While the article was certainly very chart heavy, it is probably the best way to present the data that the working group found, as they were very thorough in addressing a number of clinical scenarios for each ancillary modality that they addressed. This seems to be not only a very thorough way to address these topics but a very usable way to present the information to those in practice who will be looking for an “at a glance” way to determine test appropriateness.

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@JRamirezMD said that the suggestions published were not very different from the way that he currently practices, and others seemed to echo his statements about their own practice habits.

The authors say, and the participants of September 2018 #dermpathJC seemed to agree, this is a good place to start, but that these sorts of guidance works will need to evaluated periodically as technology changes and with the more evidence based support the better. Types of works like these are important for political reasons as well as self policing is an important part of appropriate medical practice in this day and age.

Until next month, #dermpathJC signing off.

 

#dermpathJC August 2018 summary:

#dermpathJC August 2018:

Thursday, August 30th, 9pm EST

Article discussed: Influence of variability in assessment of Breslow thickness, mitotic rate and ulceration among US pathologists interpreting invasive melanoma, for the purpose of AJCC staging

Authors: Laura Taylor, Kyle Hood, Lisa Reisch, Joann Elmore, Michael Piepkorn, Raymond Barnhill, Stevan Knezevich, Andrea Radick, David Elder

Temporary open access available at https://doi.org/10.1111/cup.13265

Summary author: Silvija P. Gottesman, MD (@SGottesmanMD)

Journal Club Summary:

Thin melanoma, a melanoma with less than 1mm Breslow thickness. Carries a good prognosis, however 15% of melanoma deaths documented in SEER resulted from thin melanomas metastases. Patients need their frequent skin checks.

7th ed AJCC versus 8th ed AJCC melanoma classification, note changes for T1 stage.

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Highest variability in mitotic count and ulceration was rarely reported by participants and experts, as most were seen in T2+ melanoma lesions, for which a SLN biopsy is routinely indicated.

Most variability was seen in staging of thin melanomas. The study saw 18% of reference T1a assessments upstaged and 28% of T1b assessments downstaged based on mitotic count disagreement. The source of the greatest variability was the recognition of mitotic figures.

Breslow thickness AJCC 8th edition – round to 1 number after the decimal point instead of 2 as in the 7th ed.

Next #dermpathJC is in September! See you then! 🙂