#dermpathJC March 2020 summary

#dermpathJC March 2020:

Thursday, March 26th, 9 pm EST

Article discussed: Angiosarcoma, Radiation-Associated Angiosarcoma, and Atypical Vascular Lesion

Authors: David R. Lucas

Open access courtesy of Archives of Pathology and Laboratory Medicine: https://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165-133.11.1804

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

Journal Club Summary:

Angiosarcoma general points:

  • 1% of soft tissue sarcomas
  • Associated with radiation therapy, most often breast cancer
    • Also associated with chronic lymphedema, toxins (i.e. vinyl chloride), and foreign bodies (i.e. A/V fistulas)
  • Usually presents as sporadic cutaneous tumor on scalp/face of elderly
  • Reported in every anatomic site
  • Bruise-like area that ulcerates or becomes nodular
  • Often have smaller satellite lesions peripherally
  • Clinically aggressive with high morbidity, regardless of grade
    • Prognosis in sporadic cutaneous angiosarcoma correlates with high- and low- risk groups on the basis of age, epitheliod histology, necrosis, and tumor depth
  • Deep tumors can be hemorrhagic spongelike or microcystic with necrosis
  • Well-differentiated lesions can be deceptively bland, but will have some combination of hyperchromasia, mild pleomorphism, prominent nucleoli, mitotic figures, multilayering, and/or dermal collagen entrapment forming intraluminal papillary structures
  • Surgical margins may be obscured by atypical lymphatic/capillary proliferations
  • Moderate/poorly differentiated types will often have heterogeneous cytoarchitectural features
    • Some combination of epithelioid, spindled, or pleomorphic cytology
    • Some combination of vasoformative, sieve-like, kaposiform, or solid architecture
  • Undifferentiated angiosarcoma will need immunohistochemistry to confirm the diagnosis
    • CD31 = single best marker with high sensitivity and specificity
      • Diffuse, intense staining with membranous accentuation
      • Can be hard to interpret due to background blush, staining macrophages, and low-level expression in other tumor types
    • CD 34 and factor VIII = present in most angiosarcomas but not reliably in poorly differentiated
    • Cytokeratin pitfall = found in 35% of cases in one study (especially epithelioid angiosarcoma) although usually focal

Radiation-associated angiosarcoma

  • Clinically and morphologically similar to sporadic angiosarcoma
    • Latency is shorter for breast angiosarcoma
      • 5-7 years on average
      • Significant occurrence in less than 3 years which questions the 3-year rule
    • More often cutaneous than sporadic angiosarcoma
      • Erythematous plaque/patch/nodules with edema
      • Diffuse, multifocal, and extensive involvement of the breast is common
      • Median size = 7.5 cm

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Atypical Vascular Lesion (AVL):

  • Benign course; can recur; rarely progress to angiosarcoma
  • Tendency to develop further lesions, commonly AVLs
  • Present as 1 or more small, flesh-colored papules or erythematous patches arising in radiated skin
  • Histologically difficult to distinguish from well-differentiated angiosarcoma in a biopsy
  • Often resemble lymphangiomas
    • Well-demarcated proliferation of thin walled, dilated, interanastomosing channels without erythrocytes
    • Lined by attenuated or hobnail endothelial cells without atypia
  • Can resemble lymphangioendothelioma, lymphangioma circumscriptum, or both within the same lesion
  • Most are limited to the superficial and mid dermis
  • Current recommendations are to completely excise and follow for recurrence

Vascular-type AVL

  • First described in 2005 with 3 cases that resemble lobular capillary hemangioma in mammary skin after radiation
    • All 3 cases developed angiosarcoma
  • In 2008, 8 more cases were described where only one developed angiosarcoma

It is suggested that vascular-type AVL is more likely to progress to angiosarcoma than the more common lymphatic-type AVL

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Memorable tweets:

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Stay safe my friends, and we will see you next month for another dermpath journal club,

With love,

DermpathJC

#dermpathJC January 2020 summary

#dermpathJC January 2020:

Thursday, January 23rd, 9 pm EST

Article discussed: Invisible dermatosis, disgnostic discrepancy between the general pathologist and dermatopathologist

Authors: Ahmed Alhumidi, Najd Alshamlan, Mona Alfaraidi, Khaled Mohajer

Temporary open access courtesy of Journal of Cutaneous Pathology at: : https://onlinelibrary.wiley.com/doi/pdf/10.1111/cup.13554

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

Journal Club Summary:

  • Invisible dermatoses are those that have subtle histologic features but have been biopsied because of obvious clinical lesions.
  • Often, a diagnosis of no significant pathological changes or nonspecific findings will be made by a general pathologist.
  • 81 total cases were reviewed over the past 15 years where general pathologists, with experience ranging from 5-20 years, made one of the following diagnoses:
    • No specific diagnosis
    • No significant pathologic changes
    • Minimal pathologic changes
  • These cases were reviewed retrospectively and blindly by a dermatopathologist trained at a reputable center in the United States with 5 years of experience in dermatopathology.
  • Out of 81 total cases, 43 (53%) were found to have a specific diagnosis while the remaining 38 (46.9%) remained non-specific. Of the nonspecific cases, 15 (39.47%) were due to inadequacy of the specimen.
  • This study aims to highlight the diagnostic challenges of invisible dermatosis, the importance of clinicopathologic correlation, biopsy adequacy/preparation, and histochemistry.
  • Conditions that are likely to receive a nonspecific diagnosis by a general pathologist include:
    • Becker’s melanosis
      • Clinically pigmented patches
      • Shoulder, back, or chest
      • Histologically – regular elongation of the rete ridges with basal hyperpigmentation
    • Spongiotic dermatitis – intercellular epidermal edema
      • Eczema
      • Id reaction
      • Pityriasis rosea
      • Pityriasis alba (children, hypopigmented patches that can mimic mycosis fungoides)
      • Many others
    • Pigmented purpuric dermatosis (extravasated red blood cells and hemosiderin-laden macrophages)
      • Progressive pigmentary dermatosis of Schamberg (subtle deposits and scant inflammation)
      • Purpura annularis telangiectodes of Majocchi
      • Eczematoid-like purpura of Doucas and Kapentanakis
      • Pigmented purpuric dermatitis of Gougerot and Blum
    • Increased dermal mucin (often subtle, can use Alcian blue and colloidal iron stains)
      • Generalized myxedema
      • Pretibial myxedema
      • Lichen myxedematosus
      • Papular mucinosis
      • Reticular erythematous mucinosis
      • Self-healing juvenile cutaneous mucinosis
      • Scleroderma
    • Pityriasis/tinea versicolor (caused by Malassezia furfur)
    • Acute generalized exanthematous pustulosis (AGEP)
    • Mycosis fungoides (cutaneous T-cell lymphoma)
    • Urticaria (if resolves within 24 hours; if chronic, suspect urticarial vasculitis)
    • Primary cutaneous amyloidosis (HMWCK+)
    • Vitiligo
    • Telangiectasia macularis eruptive perstans (TMEP; mastocytosis, highlighted by Giemsa, toluidine blue, and CD117)

jan1 This pie chart illustrates the types of diagnoses were rendered by dermatopathologists when they reviewed pathology slides without significant pathology or no diagnosis report.

 

Memorable Tweets:

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Differential diagnosis of invisible dermatoses. A mnemonic by @SGottesmanMD.Diqgo74U0AAz3dh

 

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

We are always here for you and your dermatopathology learning,

 

DermpathJC

#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)

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