#dermpathJC October 2019 summary

#dermpathJC October 2019:
 

Thursday, October 24th, 9pm EST

Article discussed: Gene expression profiling of lichenoid dermatitis immune‐related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response

Authors:Curry JL, Reuben A, Szczepaniak-Sloane R, Ning J, Milton DR, Lee CH, Hudgens C, George S, Torres-Cabala C, Johnson D, Subramanya S, Wargo JA, Mudaliar K, Wistuba II, Prieto VG, Diab A, Tetzlaff MT

Temporary open access courtesy of Journal of Cutaneous Pathology at: https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13454

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

 

Journal club summary:

Background: Patients receiving checkpoint inhibitors (CPIs) may develop a number of immune‐related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism underlying the emergence of these irAEs remains poorly understood. The current study aims to determine the unique gene expression profiles and immune composition in LD—irAE.

Study design:

Gene expression profiling on a series of LD—irAE (n = 3) and compared them with a series of sporadically occurring benign lichenoid keratosis (BLK) (n = 3). Profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. IHC analysis was performed. Benign lichenoid keratosis and Lichenoid dermatitis (immune-related adverse event) show indistinguishable histologic features.

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Results and discussion:

LD—irAE exhibit upregulation of CD14 mRNA transcripts and TLR as compared with BLK control

Lichenoid dermatitis 2/2 immune-related adverse event exhibits upregulation of CD14 mRNA (a marker of monocyte and co-receptor for TLRs), higher numbers of CD14+ and CD16+ monocytes, downregulation of CD83 (a marker of mature dendritic cells), upregulation of chemotactic molecules, CXCL12 and CCL14.

Representative immunohistochemic stains for CD14, CD16, T‐Bet, Gata‐3, and FoxP3 in benign lichenoid keratosis (BLK) control (left) and LD—irAE (right)

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TLRs – Toll like receptors are important mediators of the innate immune system response. Gene profiling of lichenoid dermatitis 2/2 immune-related adverse event bx showed upregulation of TLRs, CD14/TLR signaling pathway and MAPK.

LD—irAE exhibits a Th1 immune profile

The rationale for the statement above is the following:

T‐Bet is a known driver of pro-inflammatory responses (Th1), while GATA-3 is a known driver of anti-inflammatory responses (Th2)  and FoxP3 (forkhead box P3) is a known T regulatory cells marker (Treg).

  • LD-irAE exhibited lower Th2 expression as compared with BLK
  • LD-irAE exhibited higher Th1 expression than Th2 expression overall
  • LD-irAED exhibited lower FoxP3 expression as compared to BLK

Conclusion:

  • There is activation of the innate immune response through CD14/TLR signaling pathway in LD—irAE.
  • LD—irAE may be related to checkpoint inhibitor therapy effect on CD14/TLR signaling of CD14+CD16+ monocytes recruited to the skin.
  • Additional immune pathways involved in the development of LD—irAE include activation from skin microbiome, cytokines, and recruitment of CD14+CD16+ monocytes possibly initiate an inflammatory reaction that results in LD (summarized in the diagram below)

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Some Highlights from the Evening:

 

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Thank you so much for attending and for reading this summary. Hope you enjoyed the energy of this journal club,

We are always here for you and your dermatopathology learning,

DermpathJC

 

 

 

 

#dermpathJC September 2019 summary

#dermpathJC September 2019: 

Thursday, September 26th, 9pm EST

Article discussed: An Immunohistochemical Panel to Differentiate Metastatic Breast Carcinoma to Skin From Primary Sweat Gland Carcinomas With a Review of the Literature

Authors: Marian Rollins-Raval, MD, MPH; Mamatha Chivukula, MD; George C. Tseng, ScD; Drazen Jukic, MD, PhD; David J. Dabbs, MD

Open access at: https://doi.org/10.5858/2009-0445-OAR2

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

Journal Club Summary:

Cutaneous metastases of breast cancer (CMBCs) is observed in 25% of patients diagnosed with breast carcinoma and can be difficult to distinguish from sweat gland carcinomas (SGCs). Panel of eight IHC stains were used in four group of cases; ductal CMBCs (12 cases), SGCs (12 cases), benign sweat gland neoplasms (2 cases) and breast cancer cases (2 cases).

Discussion:

  • The authors first started by performing a literature review on previous studies and have concluded the following:
  1. ER, PR, CK7, and CK20 stains are not useful markers to differentiate the two entities.
  2. GCDFP-15, carcinoembryonic antigen, EGFR, CK5/6, podoplanin, and p63 are potential candidates and three stains from this list were further investigated in the current study (GCDFP-15, CK5/6, and p63)
  • CK14, CK17, AR, mammaglobin, and PAX5 were investigated in this study in addition to the three described above.
  • Out of the 8 stains that were investigated, only P63 and CK5 demonstrated sustained potential in distinguishing CMBC from SGC.
  • combining mammaglobin, p63 and CK5 with CK14, and CK17 consistently differentiates CMBC from SGC in the cases reviewed in this study.
  • Limitations of the study included number of cases reviewed which is understandable given the rarity of these neoplasms. Moreover, combined with the low number of cases, heterogeneity among the groups of tumors examined and subgroups classification was another challenge of the study limiting the examination of certain subgroups (one case of basal-phenotype CMBC).

Conclusion:

  • The authors recommended a panel of five IHC composed of mammaglobin, p63, and 3 basal cytokeratins to be able to differentiate between CMBCs and SGCs neoplasms (See the table below).

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Image from Archives of Pathology and Laboratory Medicine (open access):

Image

  • P63 was expressed in 90.9% of SGCs, whereas it was expressed im 8.3% of CMBCs cases.
  • Basal cytokeratins was expressed in 90.9% of SGCs and up to 16.7 in CMBCs (0% CK14 to 16.7% of cases expressing CK5 and CK17.
  • Mammaglobin was expressed in 16% of SGCs and in 66.7% of CMBC.

In sum:

Skin primary sweat gland carcinoma generally mammoglobin-, p63+, CK5+, CK14+, CK17+ Cutaneous mets of breast carcinoma generally mammoglobin+, p63-, CK5-, CK14-, CK17- ER, PR, CK7, CK20, CEA, EGFR & GCDFP-15 stains not effective in differentiating between the two.

Some Highlights from the Evening:

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And last but not least:

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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 and have fun at the upcoming #ASDP2019.

Kind regards!

DermpathJC

#dermpathJC August 2019 summary

#dermpathJC August 2019:

Thursday, August 22nd, 9 pm EST

Article discussed: Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies

Authors: Jodi Speiser, Joy Tao, Amanda Champlain, Lauren Moy, Monica Janeczek, Reeba Omman, Kumaran Mudaliar, Rebecca Tung

Temporary open access courtesy of Journal of Cutaneous Pathology at: https://doi.org/10.1111/cup.13462

Summary prepared by: Cacey Peters, M.D. (@caceypeters)

Journal Club Summary:

  • Overlap between melanocytic hyperplasia (MH) and junctional lentiginous melanocytic proliferations (JLMP) and melanoma in situ (MIS) can be a significant diagnostic dilemma.
  • Further complication arises from variability in diagnostic criteria among pathologists leading to over and under-diagnosis.
  • Lentigo maligna (LM) is a subtype of MIS that grows on chronically photodamaged skin, predominantly on the head and neck.
  • In an established lesion, LM is histologically defined as a junctional proliferation of confluent single cells and nests of large atypical melanocytes, which may demonstrate focal upward pagetoid spread.
  • In contrast, the background nonlesional photodamaged skin displays melanocytic hyperplasia (MH) and cytologic enlargement and mild pleomorphism.
  • This study used formalin-fixed paraffin-embedded staged mapped excision from a “slow Mohs” procedure in tandem with baseline scouting biopsies of adjacent non-lesional photodamaged skin to assist in determination of surgical margin clearance.
  • The advantages for this technique include entire margin assessment and the need for specific additional excision, as well as better cosmetic outcomes.
  • The lesional and photodamaged control biopsies from the same patient were compared using nuclear IHC stains to assess clinically relevant histologic criteria that may be used to distinguish photodamaged skin from JLMP and MIS.
  • Inclusion criteria included patients (a) with a previous biopsy-confirmed JLMP or MIS (lentigo maligna or superficial spreading subtypes) in a cosmetically or surgically challenging location that was available for review, (b) whose biopsy included an IHC stain for MiTF or Sox-10 and (c) who were eligible for staged excision.
  • Exclusion criteria included patients with previous biopsies that were unavailable for review or without IHC stain for MiTF or Sox-10, palpable areas within the lesion, cervical lymphadenopathy, an invasive component on initial biopsy or any contraindication for staged excision
  • The combination of histologic and clinical features aid in differentiating benign melanocytic junctional proliferations from lesions described as AJMP include more advanced patient age, presence of background sun damage, lentiginous melanocyte clustering, increased melanocytic density, lack of upward spread, lack of definitive confluence (>3 consecutive melanocytes), and no/minimal nests.
  • The clinical management of each entity has been highly debated.
  • The NIH recommends a 5 mm margin on surgical excisions but has been had mixed success on proven adequacy.
  • Staged excisions generally have high cure rates, with two studies reporting recurrence rates of 1.7% and 2.2%, respectively, although utilizing less specific IHC stains as this study.
  • Creation of specific criteria and definitions of LM, JLMP/MIS have been revised over the decades, originating from Ackerman et al who were the first to propose a set of 12 criteria which included:
    • Pagetoid spread (MIS) vs melanocytes situated at the dermal-epidermal junction (MH)
    • Irregular MH (MIS) vs regular MH (MH)
    • Deep adnexal involvement (MIS) vs superficial adnexal involvement (MH)
    • Confluence of melanocytes (MIS) vs absence of confluence (MH)
    • Presence of junctional nests (MIS) vs absence (MH)
    • Uniform (MIS) vs nonuniform pigmentation (MH)
    • Flat rete ridges (MIS) vs preserved rete ridges (MH)
    • Pleomorphic melanocytic nuclei (MIS) vs uniform nuclei (MH)
    • Prominent melanocytic dendrites (MIS) vs inconspicuous dendrites (MH)
    • Markedly large and atypical nuclei (MIS) vs large but mildly atypical nuclei (MH)
    • Collapse of cytoplasm around melanocytic nuclei (MIS) vs absence of this feature (MH)
    • Abundant melanophages (MIS) vs few or no melanophages (MH)
  • Subsequent criteria suggested in the literature were:
    • Large, elliptical and irregular nuclei via nuclear morphometry
    • 10% to 20% proliferating melanocytic cells by staining with PCNA or Ki-67/MIB-1
    • Presence of HMB-45 positive melanocytes.
  • Weyers et al evaluated the sensitivity and specificity of all the above criteria, establishing that the most valuable criteria for differentiation were:
    • Presence of nests
    • Irregular MH
    • Deep adnexal extension of melanocytes
    • Pleomorphism of melanocytes
    • Pleomorphism of melanocytic nuclei
  • IHC criteria have been proposed using Mart-1/Melan-A, MiTF and Sox-10 stains to evaluate LM, benign lesions on sun-damaged skin, and background sun damage.
  • MiTF or Sox-10 (nuclear stains) are preferred as to avoid overestimation of melanocyte density with Mart-1/Melan-A (cytoplasmic stain)
  • Photodamaged skin show many criteria originally used for MIS:
    • Increased and irregular melanocyte density
    • Melanocyte confluence
    • Stacking
    • Thèque formation
    • Adnexal extension
    • Suprabasilar scatter
  • Most of these studies were cross-sectional analyses, comparing a variety of patients to each other, which made it impossible to control for factors such as geographic location, anatomic site, age, Fitzpatrick skin type, and history of sun exposure, all of which can influence baseline melanocytic density.
  • The current study found a statistically significant difference in the following histopathologic findings:
    • melanocyte density (per 1mm instead of 0.5 mm in previous studies)
    • irregular melanocyte distribution
    • clustering of melanocytes
    • follicular infundibulum involvement
    • Presence of nests
  • This study was able to control for confounding factors, such as different baseline melanocytic densities, by comparing atypical/malignant biopsies with a sun-damaged control from the same patient.
  • The photodamaged skin samples were taken at least 2 cm from the primary lesion in order to avoid any potential field effect.
  • Although time consuming, assessment of melanocyte density may be an objective and reliable method for diagnosing these complex lesions.
  • Digital imaging may eliminate the need for manual counting in the near future.

FIGURE 1 Clinical image showing clinical lentiginous lesion (after Wood’s lamp illumination) along with markings for scouting biopsies. FIGURE 2 Clinical image showing an additional peripheral surgical margin drawn approximately 5 mm away from the delineated clinical lesion. The margins are labeled like a clock face for orientation with the numbers 3, 6, 9, and 12. Two 3 mm scouting punch biopsies were taken at least 2 cm away from the original lesion.

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Memorable Tweets:

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Thank you so much for attending and for reading this summary. Hope you enjoyed the energy of this journal club,

We are always here for you and your dermatopathology learning,

DermpathJC

#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 WangMD, PhDYouli ZuMD, 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-1fllarge 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. Sardiña, George Jour, Melissa P. Piliang, Wilma F. Bergfeld

Temporary free access courtesy of Journal of Cutaneous Pathology: 10.1111/cup.13378

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:

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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 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 HabermehlMDJennifer KoMD, 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:
– Authors 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‐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.

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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

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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!