#dermpathJC June 2019 summary

#dermpathJC June 2019:

Thursday, June 27th, 9pm EST

Article discussed: Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry

Authors: Huan-You Wang, MD, PhD; Youli Zu, MD, PhD

Open access at: https://doi.org/10.5858/arpa.2016-0521-RA

Summary prepared by: Abdullah Alswied, MBBS, MRes, PhD (@AlswiedPath)

 

Journal Club summary:

Study Background: Immunohistochemical profiles of different types of mature B-cell lymphomas, including plasma cell neoplasms exhibit distinct profiles, which enable them to be correctly diagnosed. However, except for rare examples of lymphoma, immunohistochemical profiles of mature B-cell lymphomas overlap and lack specificity.

Objectives:

Three main objectives of the paper:

1- systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10.

2- review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas.

3- review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells

Discussion:

First objective:

Systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10 (Summarized in the table below).

D-HJ6kNXoAIeYnD.jpeg

A- CD5+/CD10- B-cell lymphomas:

– Two classic examples, small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL).

– Lymphoplasmacytic lymphoma (LPL) CD5 expression is anecdotal by IHC.

– Marginal zone B-cell lymphoma (MZBCL) CD5 expression is variable based on its morphologic type.

– Diffuse large B-cell lymphomas (DLBCLs) expression of CD5 is seen in 10% of the cases. It is interesting to note that these lymphomas (CD5+) have higher rates of BCL2 expression.

B- CD10+/CD5- B-cell lymphomas:

– Follicular lymphoma (FL) and Burkitt lymphoma (BL) are the 2-prototypical B-cell lymphomas expressing CD10. The authors recommend a minimal IHC panel for FL should include BCL2, CD3, CD10, and CD20; however, ideally, BCL6, CD5, and CD21 should be included as well.

– Hairy cell leukemia (HCL) and MCL can occasionally be positive for CD10. The authors noted that CD10+ expression in MCL is related to a distinct GC signature rather than an immunophenotypical aberrancy.

– DLBCL: Although approximately 90% of DLBCLs NOS are negative for CD5 and10% to 40% of de novo DLBCLs NOS are positive for CD10.

C- CD5-/CD10- B-cell lymphomas:

– The prototypic CD5-/CD10- mature B-cell lymphomas of small cell size are MZBCL, LPL, and HCL. Most DLBCLs NOS are also negative for both CD5 and CD10.

– In this section, the authors mainly focused on MALT lymphoma and recommended the addition of CD43, lamda and kappa light chains to the panel of IHC.

– Lymphoplasmacytic lymphoma is diagnosed by exclusion, and at times, MZBCL and LPL cannot be distinguished based on morphologic and immunophenotypic features alone.

– The monotypic PCs derived from B-cell lymphoma have a similar immunophenotype to B cells and differ from those of PC myeloma.

– Hairy cell leukemia is positive for all common B-cell antigens with characteristic expression of annexin A1.

– After excluding CD5+ and/or CD10+ DLBCL NOS, approximately 50% to 70% of de novo DLBCLs NOS are negative for both CD5 and CD10.

Second Objective:

Review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas.

– CD38 and CD138 can not differentiate neoplastic PCs derived from PCM from PCs derived from B-cell lymphomas.

– By flow cytometry, CD19 provided the best criterion for distinguishing between these 2 types of neoplastic PCs as neoplastic PCs from B-cell lymphomas are positive for CD19 and are almost always negative in neoplastic PCs from PCM.

– The combination of BCL1, CD19, CD45, CD56, and CD117 is sufficient to distinguish PCs derived from PCMs and/or plasmacytomas from B-cell lymphomas, even in cases in which there is exuberant plasmacytic differentiation

Third objective:

Review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells.

– Lymphomas discussed in this sections include, plasmablastic PCM; plasmablastic lymphoma (PBL); primary effusion lymphoma (PEL); large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease, and ALK+ large B-cell lymphoma

– CD38, CD138, and MUM1 are positive in all cases of plasmablastic PCM, PBL, and PEL.

– Plasmablastic PCM and PBL cannot be separated from each other based on an IHC panel that includes CD45, CD79a, CD56, and PAX5 and the authors recommend the utilizations of CD19.

– The authors provided no recommended panel for PEL other than utilizing the clinical history and HHV8 immunostain.

– ALK+ large B-cell lymphoma is typically negative for most of the common B-cell antigens but positive for PC markers such as CD138, VS38, EMA, and MUM1.

Conclusion:

1- the presence or absence of CD5 and CD10 expression should be included in the initial immunohistochemistry screening panel for mature B-cell lymphomas, appropriate and judicial use of other B-cell antigens is necessary to ensure correct diagnoses.

2- Plasma cells from plasma cell neoplasias and B-cell lymphomas exhibit overlapping but relatively distinct immunophenotypes; thus, a panel of immunohistochemical markers (CD19, CD45, CD56, and CD117) can be employed for their proper identification.

3- CD138 staining results are almost always positive in a group of aggressive B-cell lymphomas with plasmablastic features, including plasmablastic plasma cell myeloma, plasmablastic lymphoma, andALK-1Ô¨ālarge B-cell lymphoma.

Some Highlights from the Evening:

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Thank you so much for attending and for reading this summary. We are so excited to plan yet another journal club for next month. Stay tuned.

Kind regards!

DermpathJC

#dermpathJC April 2019 summary

#dermpathJC April 2019: 

Thursday, April 25th, 9pm EST 

 

Article discussed: Erythema elevatum diutinum a rare and poorly understood

cutaneous vasculitis: A single institution experience

 

Authors: Luis A. Sardi√Īa, George Jour, Melissa P. Piliang, Wilma F. Bergfeld

 

Summary prepared by: Juanita Duran, MD; Pathology resident, PGY-3 (@JDuranMD)

 

Journal Club summary:

  • EED is a rare and chronic vasculitis of unknown etiology with variable clinical presentation.
  • The initiation of the disease is believed to occur via activation of cytokines, especially interleukin 8.
  • Its pathogenesis remains unknown, but a leading theory postulates an immune complex-mediated vasculitis (type III hypersensitivity) as the underlying phenomenom (idiopathic or related to immune diseases).
  • Reported associated causes: infections (viral and bacterial), rheumatologic diseases, and hematologic neoplasms.
  • Typically presents as persistent red, raised nodules, and plaques distributed symmetrically on acral surfaces.
  • Mostly involves extensor surfaces of the extremities as a spectrum of lesions.
  • Classic histologic features (although non-specific) are those of leukocytoclastic vasculitis involving the papillary and mid-dermal vessels.
  • Aging and more chronic lesions demonstrate onion skin-like fibrosis surrounding the vessels.
  • Differential diagnoses: leukocytoclastic vasculitis, granuloma faciale, and Sweet syndrome.

 

Methods:

  • Retrospective analysis of five cases of EED from a single institution retrieved over a period of 27 years (1989-2016).
  • Criteria applied for inclusion/diagnosis:
  • Lack of papillary dermal edema and microabscesses with negative direct immunofluorescence (DIF) for Immunoglobulin A deposits arguing against dermatitis herpetiformis.
  • Chronic presentation, and lack of fever arguing against an acute Sweet’s neutrophilic dermatosis.
  • Lack of small vessel deposits as well as a negative serological workup ruling out etiologies, such as mixed cryoglobulinemia and paraproteinemia.
  • Negative direct immunofluorescence except for positive granular vascular deposits of Immunoglobulin M and/or C3.

Salient histopathologic findings are depicted in the image below:

img_6247.png

Discussion:

  • EED is an uncommon but treatable skin condition
  • Various clinical and histologic mimickers exist, histologic ddx includes: bacillary angiomatosis, dermatofibroma, Sweet syndrome, pyoderma gangrenosum, granuloma annulare, granuloma faciale and Kaposi sarcoma.
  • Often associated with HIV, Hepatitis B, E.coli and Streptococcal antigens
  • In this series, women are more often affected than men.
  • One patient was asymptomatic, thus the importance of considering this diagnosis in asymptomatic patients.
  • Up to 40% of patients present with joint pain and arthritis.
  • Can show overlapping characteristics with granulomatous dermatoses and mixed connective tissue disease.
  • Associated to neoplasms (benign and malignant solid tumors)?
  • Clinicopathologic correlation is vital to render a diagnosis due to its heterogeneous presentation.

Highlights from the #dermpathJC session:

Picture1Picture2Picture3

Thank you so much for attending and for reading this summary. We are so excited to plan yet another journal club for you next month. Stay tuned.

Kind regards!

DermpathJC

#dermpathJC March 2019 summary

#dermpathJC March 2019:

 

Thursday, March 28, 9pm EST

Article discussed: Cutaneous Metastases: A Review and Diagnostic Approach to Tumors of Unknown Origin

Authors: Gabriel Habermehl, MD; Jennifer Ko, MD, PhD

Open access at: https://doi.org/10.5858/arpa.2018-0051-RA

Summary prepared by Silvija Gottesman, MD (@SGottesmanMD)

Journal Club summary:

Cutaneous mets, can present as single or multiple painless lesions (papules, nodules, ulcer) that are discovered at the same time with the primary tumor, before a diagnosis of internal malignancy or many months/years after.

Some studies say breast mets are most common to the skin, some say lung is most common, followed by head and neck and colorectal cancers. In the collective experience of the participants of #dermpathJC, it’s been breast carcinoma metastases.
Here’s an excellent workup algorithm for epithelioid cutaneous mets to the skin.
D2yfHjHUcAAL_gI.jpg
General considerations:
– p63 positive in SCC and in primary cutaneous adnexal carcinomas. CK15 & D2-40 positive in primary cutaneous adenocarcinomas over metastatic adenocarcinomas.
– As such, primary adnexal tumors will generally stain positively for CK7, CK15, D2-40, and p63 and negatively for CK20 and SOX10
– CK7+/CK20- in primary cutaneous adnexal carcinomas, variable CK7/CK20 in metastatic carcinomas.
– SOX10 positive in melanoma, neural and myoepithelial tumors.
LUNG:
– Can be proven with staining for TTF-1, CK7 and Napsin A (non-specific, will stain other tumors, such as large cell neuroendocrine and thyroid tumors).
– Pitfall: some lung adenocarcinomas may stain with Ber-Ep4.
– Small cell carcinoma will stain positive for TTF-1 and CAM5.2, and will be negative for CK7 and CK20.
– Mesothelioma will be positive for LMWK, calretinin, Wilms tumor 1, D2-40 and negative for CEA, TTF-1, and CD31.
GASTROINTESTINAL and HEPATOCELLULAR:
– Most useful initial panel consists of CK7 (non-reactive), and positive CK20 and CDX2. Gastric tumors can be commonly positive for both CK7 and CK20.
– Article seems to suggest CDX2 specific for colorectal primary. Some of the #dermpathJC participants have found this to be positive on many GI adenocarcinomas (upper and lower tract).
– Hepatocellular carcinomas are CK7 and CK20 negative, thus additional markers, such as: HepPar-1 and arginase-1 are helpful.
– In contrast, cholangiocarcinomas are CK7 positive and sometimes CK20 positive, but diffusely CDX2 negative.
GENITOURINARY:
– Renal cell carcinomas: typically nonreactive for CK7, CK20 and positive for pancytokeratin AE1/AE3, EMA, CD31, RCC and CD10. RCC mets are also positive for PAX8, however this is also positive in thyroid, Mullerian, and thymic tumors.
– Pitfalls: CD10 and EMA will stain cutaneous clear cell hidradenomas and sebaceous carcinomas.
– Chromophobe RCC will stain for PAX8, CD117, but will be negative for CD10.
– Urothelial mets: positive for HMWCK, CK7, p63, and S-100P with variable positivity for CK20 & GATA3.
– Prostate adenocarcinoma: negative for CK7, CK20, positive for PSA, NKX3.1, CD57, and Ber-Ep4.
BREAST:
– Both breast carcinomas and adenxal neoplasms are typically CK7 positive and CK20 negative.
– Breast carcinomas typically positive for: CK19, MUC1), ER, PR and mammaglobin, but nonreactive for CK5/6 and TTF-1.
– In contrast, pagetoid SCC will be p63 and CK5/6 positive, but mammary and extramammary Paget’s will be p63 negative and CK7+.
– The most useful IHC to differentiate between metastatic breast and primary cutaneous tumors – majority of the participants recommend p63 in conjunction with history and imaging. Sweat gland carcinomas strongly express p63, CK14, CK5, and CK17, however, the latter three immunohistochemical stains are not readily available in all labs.
– GATA3 stains breast carcinomas strongly, but has also been shown to be positive in trichofollicular and sebaceous neoplasms, as well as urothelial carcinoma, parathyroid gland neoplasms, salivary gland neoplasms, and pheochromocytomas.
GYNECOLOGIC:
– Ovarian and endometrial: CK7+ and PAX8+, Endocervix adenocarcinomas: CK7+ and EMA+/-. All three are CK20 negative and show variable ER and PR expression. Endometrioid morphology ddx includes pilomatrical carcinomas, in this instance p63 will be helpful to differentiate primary cutaneous adnexal neoplasm from a metastasis.
MELANOMA:
– Metastases are S100 and SOX10 positive. Melan-A and HMB-45 can be variable.
LYMPHOMA and LEUKEMIA:
РAuthors suggest that CD3, CD20, CD30 and muramidase panel is helpful for initial evaluation of atypical lymphoid infiltrates, however majority of the #dermpathJC participants agree that this is a very limited initial panel and should also include: PAX5 always for B-cells and at least 2 markers for each cel lineage.
SARCOMA:
– True metastatic sarcomas to the skin are extremely rare.
– An entity worth noting: epithelioid sarcoma, which has high metastic potential and high mortality. These show positivity for CD34 in up to 50% of cases, as well as CK AE1/3 and EMA. SMARCB1/INI1 22q11 deletion via loss of nuclear INI1 staining.
That’s all folks for now, until next #dermpathJC, stay happy and curious,
Sincerely,
Silvija Gottesman, MD

#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‚Äźcase 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
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#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 ‚Äúbulges‚ÄĚ (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 ‚Äď 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. ‚ÄúIn short, morpheaform tends to have smaller basaloid nests. But to stress again many consider them as same of overlapping features.‚ÄĚ
      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:

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

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

‚Ė† ASDP AUC used 25 yrs old as cutoff; SK very rare under that age

‚Ė† 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 )

‚óč Koilocytes helpful in diagnosing condy vs SK

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

‚óč 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)

‚óŹ HPV testing on low grade lesions:

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

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

‚óč 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

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

https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13142 ; found HPV testing¬†‚Äúrarely appropriate‚ÄĚ in many scenarios, exception being pediatric cases with path suggestive of condy (HPV testing ‚Äúusually appropriate‚ÄĚ in these cases)

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

‚óč Some only use ‚Äúcondyloma‚ÄĚ for papillomatous low grade squamous lesions in the vulva and reserve LSIL for lesions that appear flat, others use both terms (‚Äúcondyloma (LSIL)‚ÄĚ)

‚óč 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 ‚Äúflat condyloma or HPV effect‚ÄĚ 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 )

‚óŹ 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

‚óŹ Giant condy vs verrucous CA:

‚óč 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

‚óč 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‚ÄźLien 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 ‚ÄúOUT‚ÄĚ 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.

8

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 ‚Äúat a glance‚ÄĚ way to determine test appropriateness.

9

@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.