#dermpathJC September 2017 Summary:

#dermpathJC September 2017:

Thursday, September 26th, 9pm EST

Article discussed: Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases.

Authors: Machado I, Llombart B, Cruz J, Traves V, Requena C, Nagore E, Parafioriti A, Monteagudo C, Llombart-Bosch A.

Journal of Cutaneous Pathology, 2017; 44: 632638.

Free access for 3 months at: http://onlinelibrary.wiley.com/doi/10.1111/cup.12949/epdf.

Summary author: Dr. Silvija P. Gottesman (@SGottesmanMD).

Journal Club Summary:

  • Desmoplastic melanoma (DM) occurs on chronically sun-damaged skin, head and neck of elderly patients. It can mimic a scar, clinically and histologically. Cutaneous malignant peripheral nerve sheath tumor (MPNST) is rare.
  • Three challenging cases of desmoplastic melanoma were presented in this manuscript, all patient’s were over 70 years old, the lesions were on chronically sun damaged skin.
    • Case 1: 90 year old male, right cheek lesion with invasion into the zygomatic muscle. Histology showed atypical spindle cell proliferation, high mitotic index Ki-67 was 70%, extensive perineural invasion, prominent solar elastosis and atypical intraepidermal melanocytic proliferation (AIMP), S100+, nestin+, CD56+, PGP9.5+ and vimentin+ ,Mel-A- and HMB45-. The AIMP was Mel-A+ and HMB45+.
    • Case 2: 72 year old woman with right medial cheek lesion with atypical biphasic spindle cell proliferation, perineural invasion, solar elastosis, lymphoid aggregates and atypical junctional melanocytic proliferation that help sway diagnosis toward melanoma. Strong and diffuse S100+.
    • Case 3: 73 year old man with a lesion on the right index finger. S100+ spindle cell tumor with several biopsies over the course of several years as they patient was initially refusing treatment. Melanocytic differentiation  was proved with immunohistochemistry: strong S100, SOX10, Melan-A, HMB45 and MITF positivity. Final diagnosis: mixed desmoplastic melanoma undergoing progression to a higher grade.
  • Epithelioid MPNST has SMARCB1/INI1 loss, while INI1 gene is retained in DM and most spindle MPNST.
  • BRAF and RAS mutations usually absent in DM. Rarely MPNST may harbor V600E mutation.
  • Clinicopathologic and genetic findings of desmoplastic melanoma, MPNST, and cutaneous clear cell sarcoma are neatly summarized below:IMG_1594
  • Excellent paper by Plaza JA et al. PubMedID: 26661921 discussed an extended panel of immunohistochemistry for desmoplastic melanoma: all cases expressed p16, WT-1, SOX-10, nestin and S100p and 95% of cases expressed p75.
  • Another excellent paper that dissects the “often muddled and conflicting ways in which neurotropism is defined” PubMedID: 26050260Neurotropic melanoma can be used to describe any type of melanoma that has perineural involvement. PNI: Increased risk of recurrence and decreased disease free survival. Remains equivocal in melanoma. Neurotrophins and their receptors (TrkA, RET, p75NGFR, NCAM) expression in tumor cells allows for proproliferative and proinvasive response to the neural microenvironment.
  • A question arose how to differentiate desmoplastic melanoma from spindle cell melanoma. An excellent figure from nature.com Modern Pathology is enclosed:

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  • Take home points:
    • Desmoplastic melanoma occurs on sun damaged skin, on the head and neck of elderly patients. Cutaneous MPNST is rare.
    • Desmoplastic melanoma has diffuse S100+ staining, whereas MPNST has patchy S100+.
    • Serial H&E sections in search of junctional component are useful in desmoplastic melanoma cases.

Thanks to all who participated! See you in October at the American Society of Dermatopathology Annual Meeting in Baltimore, MD and back to #dermpathJC on November 30th at 9PM EST!

 

#dermpathJC August 2017 Summary:

#dermpathJC August 2017:

Thursday, August 24th, 9pm EST

Article discussed: BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia.

Authors: Linskey KRGimbel DCZukerberg LRDuncan LMSadow PMNazarian RM.

Archives of Pathology and Laboratory Medicine, November 2013, Volume 137, Issue 11, Pages 1591-8.

Free access at: http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2012-0424-OA.

Special thanks to Dr. Katy Veprauskas (@LinskeyKaty) for providing the summary below.

Journal Club Summary

Background:

  • Basaloid squamous cell carcinoma (bSCC) of the skin and aerodigestive tract shows histologic overlap with primary and metastatic basal cell carcinoma with squamous differentiation (metatypical BCC, or BCCm).
  • BerEp4 has proved to be a helpful diagnostic aid owing to its positivity in basal cell carcinoma, however is limited due to its lack of strong staining in areas of squamous differentiation.
  • Squamous cell carcinoma tends toward more aggressive clinical behavior compared with basal cell carcinoma, therefore additional markers are needed to help facilitate diagnosis.

Aim of study:

  • To test immunohistochemical markers CK14 and CK17, along with BerEp4, to determine their utility in the distinction between bSCC and BCCm.

Results:

  • A total of 25 bSCC (8 cutaneous, 12 aerodigestive tract, 5 lymph node metastases) and 43 cases of BCCm (39 cutaneous, 4 lymph node metastases) were stained with BerEp4, CK17 and CK14.
  • The mean percentage of staining was significantly higher in BCCm compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK17, P < .001).
  • The percentage of diffuse staining was also significantly higher in BCCm compared with bSCC (58% of BCCm cases displayed diffuse staining for all markers compared with no cases (0%) of bSCC).
  • Nearly all BCCm showed diffuse staining for CK17 and CK14 (98%), compared with 8% of bSCC.
  • Areas of squamous differentiation in BCCm often did not show staining with BerEp4.
  • Sensitivity, specificity, negative and positive predictive values are shown in Table 2.

6.jpg

Conclusion:

  • BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in the diagnosis.

Limitations:

  • Small sample size.
  • Single center study.
  • Conflicting reports in prior literature due to different antibodies used and different definitions of BCCm.

Twitter Journal Club Discussion Summary:

  • Some (but not all) participants have noted occasional lack of reliable BerEp4 staining of BCC
  • Most participants do not have CK14 or CK17 in their lab, but they may be available as send out stains
  • Basaloid SCC of the skin was discussed as being a rare but important entity that we would not want to miss; potential extrapolation of study results to other SCC which do not meet Wain criteria but may be moderately differentiated or have other basaloid features
  • Discussed the distinction between aerodigestive tract bSCC and HPV-related oropharyngeal SCCs; bSCC is considered a separate entity which is not HPV related (all tested negative for p16 in our study) with a worse prognosis than HPV-related OPSCC.
  • Other immunostains that participants cited as helpful in the BCC vs SCC differential include MOC31 which stains BCC and UEA-1 which stains SCC (https://www.ncbi.nlm.nih.gov/pubmed/25702956); GATA3 also mentioned but may not be as helpful (supposed to stain BCC > SCC, but may also stain adnexal tumors which may enter the differential, and can also show some staining in SCC).

Thanks to all who participated! See you in September!

#dermpathJC July 2017 Summary:

#dermpathJC July 2017:

Thursday, July 27th, 9pm EST

Article discussed: “Clonal Seborrheic Keratosis versus Pagetoid Bowen Disease: Histopathology and Role of Adjunctive Markers”

Authors: Kalegowda, Inchara Yeliur MD and Böer-Auer, Almut MD

American Journal of Dermatopathology, June 2017 – Volume 39 – Issue 6 – p 433-439.

Free access at: http://tinyurl.com/clonalinsitu for one month.

Special thanks to Dr Abha Soni (@AsoniDOfor providing the summary below.

Journal Club Summary:

Background:

  • Clonal seborrheic keratosis (CSK) and pagetoid Bowen’s disease (PBD) are two distinct diagnostic entities that can sometimes be challenging to differentiate morphologically.
  • CSK is a benign lesion and PBD is malignant–making this diagnostic differentiation necessary for appropriate clinical management.
  • Both entities are believed to belong to a common Dermatopathology pattern known as the ‘Borst-Jadasson Phenomenon.’ This represents a group of epidermal lesions with nests of clonal cells that may differ in appearance, but not histogenesis.

Aim of study:

  • The study aim was to review the histologic criteria used to differentiate CSK from PBD and evaluate the expression of a panel of immunohistochemical stains (CK10, Ki-67, and p16) within a sample of cases, in an effort to distinguish the two entities histologically.

Results:

  • A total of 29 cases of CSK and 13 cases of PBD were assessed.
  • The histological features shared by both entities were: necrotic keratinocytes and parakeratosis. However, only PBD had features of mitoses, nuclear crowding, and pleomorphism.
  • There was a statistically significant difference in suprabasal mitoses (P<0001), nuclear pleomorphism (P< 0.0001), and crowding of nuclei (P< 0.0056), all of which are more commonly expressed in PBD.
  • Also, a statistical difference was observed in the presence of broad rete ridges (P=0064), a finding which was always seen in CSK.
  • The immunohistochemistry staining for CK10 showed negative nests corresponding to the clonal proliferation of basaloid cells in CSK. However, the staining was variable in many cases showing scattered positive cells within the nests. While PBD showed nonspecific staining for CK10.
  • The immunohistochemistry staining for p16 showed moderate to strong staining in >75% of cells in the PBD nests, in mostly negative staining in CSK.
  • The Ki-67 index consistently displayed positive cells within the upper third of the lesional epithelium in PDB, a feature not observed as frequently in CSK.

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Discussion:

  • Morphological findings like nuclear atypia, crowding, pleomorphism, and mitotic figures are more frequently encountered in PBD than CSK and useful in making a diagnostic distinction between the two entities.
  • CK10 is studied as a prominent marker of suprabasal differentiation. This observation was reflected in the current study by showing CK10 negative staining in the nests of CSK cases but not PBD cases, supporting the thought that CSK nests show a phenotype related to basal keratinocytes.
  • p16 acts as tumor suppressor gene and in the current study was expressed only in the PBD cases. However, studies showing p16 staining in SK are limited and the overall results are variable in literature.
  • Ki-67, a marker of proliferative index was logically more positivity in PBD over CSK cells, supporting findings in previous literature. However, an interesting finding in this study showed that there was a difference in localization of the Ki-67 positive cells in the upper third of the epithelium in PBD.
  • Previous studies have described the development of Bowenoid disease in a seborrheic keratosis. However, they are unable to distinguish whether this is a causative or collision phenomenon.

Conclusion:

  • The study concludes that neither histological parameters nor IHC alone is sufficient enough to distinguish CSK from PBD.
  • They believe that a confident distinction can only be made when using findings of both histology and IHC studies together.

Limitations:

  • Single center study
  • Small sample size
  • Inter-observer variability in interpretation of staining and limited literature to support findings.

Twitter Journal Club Discussion Summary:

  • The majority agree that it is a challenging differentiation, but prefer and rely on histological parameters to differentiate between the two diagnostic entities.
  • When absolutely needed a Ki-67 is most commonly used by the practicing dermatopathologists for IHC assistance.
  • Some practicing dermatopathologists prefer to explain their findings in a comment and call the lesion:
    • “Seborrheic keratosis with squamous atypia,”à If favoring seborrheic keratosis.
    • “Atypical squamous proliferation, can’t exclude SCC”à If it is challenging to favor one over the other.
  • Although uncommon, there have been cases of Bowenoid transformation of seborrheic keratosis. This diagnosis has to be carefully made and commented on as it can be misinterpreted by patients that all seborrheic keratosis are pre-malignant.

Twitter #dermpathJC Fun Fact: Ki-67 is pronounced “Kee-67”. Discovered in 1983 by Prof Harald Stein from Kiel, Germany. It’s named after the city.

Thank you all for participating! Please join us again next month!

#dermpathJC June 2017 Summary:

#dermpathJC June 2017:

Thursday, June 29th, 9pm EST

Article discussed: “SOX10 immunohistochemistry in sweat ductal/glandular neoplasms.”

Authors: Cassarino D, Su A, Robbins B, Altree-Tacha D, Ra S.

Journal of Cutaneous Pathology, June 2017.

Free access at:  for 2 months.

Special thanks to Dr Annie Morrison (@AnnieMorrisonMDfor providing the summary below.

Journal Club Summary:

Background: Sox10 is a relatively new IHC stain that is used as a melanocytic and schwannian marker.

Prelim observation/previous study: Sox10 IHC positive in eccrine glands and negative in eccrine ducts, apocrine glands, and hair follicles

Hypothesis: Sweat gland tumors of suspected eccrine origin would show Sox10 expression while apocrine-derived sweat gland tumors would not.

Methods: 90 sweat gland tumors (all with classic histopathology) and 13 basal cell carcinomas evaluated:

Cylindroma 10

Spiradenoma 13

Syringocystademona papilliferum 10

Hidradenoma papilliferum 10

Poroma 12

Syringoma 10

Apocrine adenoma 10

Hidradenoma 15

Stain used: anti-Sox10 antibody (clone BC34: Biocare Medical,, Concord, California; dilution 1:20)

Stain evaluation: percentage of tumor cells (semiquantitative) and staining intensity (0, 1+, 2+, 3+) recorded.

Results Table:

Screen Shot 2017-07-03 at 1.28.27 AM.png

Discussion highlights: Strong diffuse positivity for Sox10 in cylindroma and spiradenoma and the complete absence of Sox10 staining in BCC may be helpful in the setting of a small, superficially sampled, and/or poorly oriented or fragmented specimen.

Sox10 staining in SCAP and HAP: diffuse myoepithelial cell staining, not unexpected

Myoepithelial cells: + Sox10 in normal salivary glands & ducts, salivary gland tumors, breast lobules, cutaneous myoepitheliomas, and cutaneous mixed tumors with predominate myoepithelial components.

SCAP, HAP, and apocrine adenomas: focal + Sox10 in apocrine epithelial cells, unexpected

New hypothesis: Sox10 expression may be upregulated in a portion of the lesional cells

Poroma & syringomas: Sox10 negative, expected

Both believed to be derived from sweat ducts

Hidradenoma: heterogenous Sox10 staining; somewhat expected

Hidradenomas are heterogenous tumors, two cell types (clear cells & dark/eosinophilic cells)

Weak/negative Sox10 staining appeared more common in lesions/areas with clear cell predominance.

Limitations of study:

Small sample size

Limited lesions evaluated (another study planned to look at follicular tumors and adnexal carcinomas)

Twitter Journal Club Discussion Summary:

A significant number of #dermpathJC participants use Sox10 with or without S100protein to distinguish melanocytic/neural lesions from other lesions, and/or in sentinal lymph nodes for melanoma.

Sox10 has been used by some participants to evaluate adenoid cystic carcinoma

Sox10 is negative in PEComas, fibrohistiocytic and histiocytic proliferations.

A known Sox10 pitfall is occasional staining in scars, particularly concerning when evaluating desmoplastic melanomas.

From this paper Sox10 does not appear to help distinguish between eccrine and apocrine differentiation in adnexal lesions. Histomorphology is still the “gold standard”.

Study confirms: Sox10 stains myoepithelial cells in cutaneous adnexal lesions.

The results of the pending study of Sox10 expression in follicular tumors and adnexal carcinomas is of interest to many participants.

More studies/references are needed to further characterize Sox10 expression in adnexal lesions.

Diagram of Sox10 role in neural crest cell migration:nrm2428-i1

Fun fact: SOX10 aka SRY-related HMG-box. SOX10 gene expression regulated by MITF in melanocytic lesions.

Interesting Link: Music from SOX10 protein sequence: https://www.youtube.com/watch?v=rA126rgymAo

See y’all next month!

#dermpathJC May 2017 Summary:

#dermpathJC May 2017:

Thursday, May 25th, 9pm EST

Article discussed: “Cutaneous Plasmacytosis: A Clinicopathologic Study of a Series of Cases and their Treatment Outcomes.”

Authors: Han X, Lee S, Tan S, Chong W, Ng S, Ooi M and Goh C.

American Journal of Dermatopathology, 2017.

Free access at:  from MAY21 to JUNE21!

Special thanks to Dr Adrienne Jordan @JordanDermPath for providing the summary below.

Journal Club Summary:

Review of the article:

1. Cutaneous plasmayctosis presents clinically as reddish brown nodules on the trunk of adults; most common in Asians; chronic course (lesions present for 2-10 years)
a. Axilla is almost always involved
b. Elevated serum immunoglobulins (IgG most common)
c. Elevated Kappa and lambda free light chains, but Kappa to lambda ratio is preserved
2. Histology:
a. Perivascular dermal infiltrate of mature polyclonal plasma cells; no atypia
b. Mast cells are increased (some are degranulating)
c. Increased basal melanin pigment
d. Vascular proliferation common
e. Psoriasiform epidermal hyperplasia
f. Lymphoid follicles may be present
g. HHV8 and EBV negative
3. Treatment:
a. Mask bath PUVA
b. Oral antibiotics
c. Topical and intralesional steroids
d. Topical tacrolimus
4. Poor prognostic factors:
a. IgG > 5000 mg/mL
b. High plasma cell count in bone marrow
5. Differential diagnosis
a. Secondary syphilis: Spirochetes seen on Warthin Starry stain or IHC
b. Rosai Dorfman: Infiltrate also has abundant histiocytes and emperipolesis
c. Plasmacytoma: monoclonality and plasma cell atypia
d. MZBCL: very difficult distinction; monoclonality (specifically performing heavy chain gene rearrangement studies) may be helpful

Review of Journal Club Discussion:
1. It was hypothesized that since IL-6 is increased in patients with CP and IL-6 receptors are localized on melanin this explains the increased basal melanin pigmentation
2. Castlemans disease and plasma cell granuloma were added to the list of differential diagnoses
3. Although not reported in this series, other articles have commented on perineural plasma cells being prominent in CP
4. Although other papers have described an increased IgG4, participants agreed that CP is not part of the IgG4 diseases as sclerosis is not generally a feature of CP as it is in the IgG4 diseases
a. If sclerosis is present, one should consider a plasma cell granuloma
5. Very nice chart provided to help differentiate plasma cell infiltrates in the skin:

Screen Shot 2017-05-30 at 6.53.44 PM

Next #dermpathJC is set for 5/25/17 at 9PM EST. We will be featuring the following article by Dr Han et al. PDF at https://tinyurl.com/kq8vzdb.

We are so thankful to the American Journal of Dermatopathology for their support!! FREE access from MAY21 to JUNE21! You can download the PDF at the link above.

Just remember, to follow the discussion all you need to do is search for the #dermpathJC hashtag on the allotted date and time (5/25/17 9PM EST). You can also tag our @dermpathJC twitter handle. If you want to contribute to the discussion and leave a comment, you will need to open a Twitter account.

We are excited for you to join us.

 

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#dermpathJC April 2017 Summary:

#dermpathJC April 2017:

Thursday, April 27th, 9pm EST

Article discussed: “Acantholytic invasive squamous cell carcinoma: tumor diameter, invasion depth, grade of differentiation, surgical margins, perineural invasion, recurrence and death rate.”

Authors: J.H. Pyne, E. Myint, E. M. Barr, S. P. Clark, M. David, R. Na.

Journal of Cutaneous Pathology 2017: 44: 320-327.

Access at: http://onlinelibrary.wiley.com/doi/10.1111/cup.12869/full

 

Journal Club Summary:

Acantholysis (definition): loss of intercellular adhesion between keratinocytes (not intracellular).
Acantholytic SCC may be referred as adenoid SCC, adenoacanthoma, or pseudoglandular SCC. 1st described by Lever in 1947.
Even though it had “pseudoglandular appearance, the acantholytic phenomenon was entirely squamous in nature.
Acantholytic SCC has been more of a histological fascination and not a prognostic one.
Conflicting early papers with closing thoughts that acantholytic SCC could be prognostically bad. Those studies had low power.

Acantholytic SCC:
has been described as an intermediate risk SCC
more prevalent in male patients (male pattern baldness/increased risk of sun damage link perhaps?)
on chronically sun damaged skin such as the head & neck

Which histologic factors indicate higher-risk invasive SCC?
increased tumor diameter
increased tumor depth of invasion
shift towards poor differentiation
Perineural invasion – goes in the report if there

European guidelines for treatment of SCC – from 2015
low-risk SCC – treat with 5mm margin
high-risk SCC – treat with 10mm margin

US treatment guidelines for treatment of SCC of the skin:
Low-risk SCC use 4-6mm margin. If high risk, wider margins or Mohs.
NCCN 2017 guidelines talk about adenoid (acantholytic) SCC as a marker of an increased risk of recurrence or metastasis – Nappi et al. 1989
High risk marker for local recurrence or metastases

Pyne et al. Results:
total of 1656 invasive SCC identified for the study
4.9% cases (82 total) had acantholysis
confirmed independently by 2 pathologists
no significant difference in relation to sex and grade of differentiation bw acantholytic SCC and non-acantholytic SCC
median age (72 years) was similar for both patient groups (with and without acantholysis)
Site most favored for acantholytic SCC (head and cheek/chin)
Site most favored for non-acantholytic SCC (leg – particularly lower leg and forearm) – keratoacanthomatous morphology (from journal club)
Depth of non-acantholytic SCC was significantly deeper than acantholytic SCC: 1.5mm vs 1mm (p<0.001).
Shift from well to poor differentiation did not correlate with an increase in the acantholysis percentage.
Median follow up 25 months for 77 cases

Limitations:
single center study
SCC driving etiology was chronic sun exposure etc.

Discussion:
metastatic potential – SCC diameter of at least 15mm and depth of at least 2mm
poor differentiation and/or increased tumor depth may have confounded recurrence, rather than just the presence of acantholysis alone.
Nappi et al did nit find any PNI in any case of an acantholytic study (1989).

Conclusion:
More appropriate measures of aggressive behavior for SCC: mortality, metastasis and perineural invasion
Low perineural invasion, low recurrence rates, no deaths on followup, may prompt us to think of acantholytic SCC as a low-risk tumor.

I want to extend a special Thank You to Dr. Shea and @JCutaneousPath for their support in making this article open-access for two moths for our first dermpath journal club!

Thank you all for participating,

Sincerely,

Silvija P. Gottesman, MD