#dermpathJC December 2019 summary

#dermpathJC December 2019:

Thursday, December 5th, 9 pm EST

Article discussed: Dermatologic Urgencies and Emergencies: What Every Pathologist Should Know

Authors: Mallory S. Abate, MD; Laura R. Battle, MD; Ashley N. Emerson, MD; Jerad M. Gardner, MD; Sara C. Shalin, MD, PhD

Open access courtesy of Archives of Pathology at: https://www.archivesofpathology.org/doi/10.5858/arpa.2018-0239-RA

Summary prepared by: Mitul B. Modi, MBBS, MD (@MitulModiMD)

 

Journal club summary:

Background:

Dermatologic diseases with high morbidity can occur in the inpatient setting. In these circumstances, bedside skin biopsy, although challenging could be the most important guiding tool for accurate assessment, especially for pathologists not experts in dermatopathology. This unique review represents a collaborative opinion from both dermatology and a dermatopathology view.

Review:

Herein, with this article authors are providing a reference guide on dermatologic urgencies and emergencies, focusing on diagnostic pearls, pitfalls, and commonly encountered practice scenarios. The key diseases focused in this article are angioinvasive fungal infections, Stevens-Johnson syndrome/toxic epidermal necrolysis, staph-scalded-skin syndrome, acute graft-versus-host disease, bullous pemphigoid, calciphylaxis, Sweet syndrome and its histiocytoid variant, pyoderma gangrenosum, and leukocytoclastic vasculitis, as well as those in their clinical and histopathologic differential.

ANGIOINVASIVE FUNGAL INFECTIONS

High-yield points:

  • Rapidly progressive in immunosuppressed or trauma patients with high mortality.
  • Hematoxylin-eosin (H&E) reveals fungal hyphae in the dermis and/or vessels +/− epidermal and/or dermal necrosis.
  • Periodic acid–Schiff (PAS) or Gomori methenamine silver (GMS) is performed in all suspicious cases.
  • Speciation cannot be performed based on histopathology alone.

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STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS

High-yield points for SJS and TEN:

  • Life-threatening skin disorder with full-thickness epidermal sloughing of the skin and mucous membranes.
  • First step in treatment is immediate identification and withdrawal of causative drug.
  • Can mimic erythema multiforme (EM) histologically, requiring clinical differentiation.
  • Differentiated from SSSS both clinically and histologically because of the more superficial level of blistering in SSSS.

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ACUTE GRAFT-VERSUS-HOST DISEASE

High-yield points for aGVHD:

  • Nonspecific morbilliform eruption in HSCT patients.
  • Hematoxylin-eosin reveals vacuolar interface dermatitis.
  • In early stages it can be histologically indistinguishable from other common rashes like viral exanthems or drug eruptions in the posttransplant period.

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BULLOUS PEMPHIGOID

High-yield points for BP:

  • Subepidermal blistering disease most commonly seen in the elderly.
  • Characterized by tense bullae clinically, which correlate to cleavage along the basement membrane zone histologically.
  • Definitive diagnosis is made by immunofluorescence studies.

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CALCIPHYLAXIS

High-yield points for calciphylaxis:

  • Tissue ischemia that develops as a serious complication in patients with end-stage renal disease (ESRD) on dialysis.
  • Hematoxylin-eosin reveals thrombotic vasculopathy in small (often subcuticular) vessels, with basophilic calcium deposits in the deep dermis and subcutis, associated inflammation, and/or tissue necrosis.
  • Von Kossa or alizarin red should be performed in all suspicious cases.

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SWEET SYNDROME (ACUTE FEBRILE NEUTROPHILIC DERMATOSIS)

High-yield points for Sweet syndrome:

  • Erythematous “juicy” papules on the head, neck, and upper extremities.
  • May be associated with underlying malignancy, infection, or medications.
  • Hematoxylin-eosin reveals marked papillary dermal edema with abundant neutrophils.
  • Despite clinical presentation and histopathology that may suggest an infectious etiology, all infectious workup will be negative.
  • Excellent response to corticosteroids.
  • A diagnosis of histiocytoid Sweet syndrome should be made with caution and leukemia cutis must be excluded.

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HISTIOCYTOID SWEET SYNDROME

High-yield points for Histiocytoid Sweet syndrome:

  • Indistinguishable from classic Sweet syndrome clinically
  • histiocytoid Sweet syndrome is histologically distinct and characterized by an infiltrate of mononuclear cells that have a histiocytic appearance;
  • histologically mimicker of leukemia cutis

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PYODERMA GANGRENOSUM

High-yield points for PG include the following:

  • A “neutrophilic dermatosis” that presents with rapidly progressive skin ulcerations.
  • Commonly misdiagnosed, which can result in devastating tissue loss.
  • Histology is nonspecific and the inflammatory infiltrate can vary with location of biopsy and duration of lesion.
  • Infection by bacteria, fungi, or acid-fast bacteria must be excluded by either special stains, microbial cultures, molecular techniques, or a combination of these.

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CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS

High-yield points for cutaneous LCV include the following:

  • Represents a distinct histologic inflammatory pattern affecting small vessels of the dermis.
  • Corresponds to the clinical diagnosis of cutaneous small vessel necrotizing vasculitis and classically manifests as palpable purpura.
  • Can be seen in a variety of primary vasculitic dermatoses or as a secondary finding in nonvasculitic dermatoses; clinicopathologic correlation is required.

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Summary

  • This article has highlighted the pivotal role that pathologists/dermatopathologists play in dermatologic urgencies and emergencies. This, in turn, can be helpful in providing accurate histologic diagnoses with improved patient care in a timely manner.
  • This review thus serves as a practical reference guide for any pathologist while working up a rush inpatient skin biopsy. In emergency cases and scenarios, an initial discussion and an open line of communication between a dermatologist with the pathologist is important for providing a histologic diagnosis in a timely manner.
  • As soon as the slides have been processed, it is helpful to hear the pathologist’s initial impression of the biopsy as well as of any positive, negative, and pending stains. This way of continued conversation with the dermatologist can help narrow the differential diagnosis and ultimately help the pathologist/dermatopathologist to arrive at the diagnosis.
  • The takeaway point from this article is that a systemic and collaborative approach yields the best patient outcome, instead of panicking while coming across dermatologic emergencies and urgencies.

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Thank you so much for attending #DermpathJC and for reading this summary.

Hope you enjoyed the energy of this journal club,

We are always here for you and your dermatopathology learning,

Happy Holidays and Happy New Year!

DermpathJC

 

#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)

 

Background: 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)

Objectives: Recommend a panel of IHC stains to distinguish CMBC from SGC.

Design: 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 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).

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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