#dermpathJC April 2020 summary

#dermpathJC April 2020:

Thursday, April 30th, 9 pm EST

Article discussed: Cutaneous carcinosarcoma: a series of six cases and a review of the literature

Authors: Joshua J. Clark, Anneli R. Bowen, Glen M. Bowen, John R. Hyngstrom, Michael L. Hadley, Keith Duffy, Scott R. Florell and David A. Wada

Open access courtesy of Journal of Cutaneous Pathology: https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.12843

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

 

Journal Club Summary:

  • Coined by Virchow in 1864, the term carcinosarcoma refers to a biphasic malignant neoplasm with epithelial and mesenchymal components which can be seen in virtually every organ
  • In primary cutaneous carcinosarcoma, the most common epithelial components are basal cell and squamous cell carcinomas, whereas the less common include malignant spiradenoma, porocarcinoma, pilomatrical carcinoma, and trichoblastic carcinoma
  • The mesenchymal component includes fibrosarcoma, pleomorphic undifferentiated sarcoma (previously called malignant fibrous histiocytoma), osteosarcoma, chondrosarcoma, and rhabdomyosarcoma
  • Although cutaneous carcinosarcomas are rare, they are likely under-reported due to lack of awareness, tissue sampling variation, and the variety of clinical/histological phenotypes
  • Of the reported cases reviewed, most occurred on sun-exposed areas of the head and extremities with age ranges from 32 to 98 years old, most cases occurring in the 8th and 9th decades of life
  • Male predominance was found to be 1.7:1
  • Recurrence and death were more common from adnexal carcinosarcomas with equal distribution among the various adnexal groups
  • Patients with basal cell carcinosarcoma had longer disease-free survival than those with squamous cell carcinosarcoma
  • The two hypotheses of the origin of carcinosarcoma include a monoclonal carcinoma that undergoes metaplasia with loss of residual epithelial differentiation versus a convergence of two or more distinct progenitor cells
  • Multiple molecular studies of non-cutaneous carcinosarcomas favor a monoclonal cell population with differentiation into both epithelial and mesenchymal components
  • Basal cell carcinosarcoma has been shown to be related to sun damage with mutations in PTCH1, p53, p63, and p13 genes
  • Squamous cell carcinosarcoma has been shown to have point mutations and deletions in the TP53 gene
  • The main histologic differential diagnosis of malignant biphasic neoplasms includes sarcomatoid carcinoma, malignant mixed tumor, biphasic synovial sarcoma, and malignant peripheral nerve sheath tumor
    • Sarcomatoid carcinoma (spindle-cell squamous carcinoma) = malignant spindle cells with some degree of typical squamous cell carcinoma which can be proven with immunohistochemistry (IHC) for keratins and/or p63 by the spindle cells
    • Biphasic synovial sarcoma = uncertain histogenesis; extremities; young adults; epithelial cells in cords/nests/glands with admixed cellular, monotonous spindle cell proliferation; confirmed with TLE1, EMA, and/or cytokeratin as well as t(X;18) translocation
    • Malignant mixed tumors of the skin = contain carcinoma admixed with benign myxoid or chondroid proliferations; may be S100+
    • Malignant peripheral nerve sheath tumor (MPNST) = rarely can have mucin-producing glands with cuboidal/columnar cells admixed with malignant spindle cells that otherwise fits criteria for the typical MPNST
  • Three diagnostic criteria have been proposed for primary cutaneous carcinosarcoma
    • Clearly defined dual neoplasm with explicit characterization via histology and IHCs
    • Exclusion of metastasis from other sites
    • Exclusion of sarcomatous stromal changes around otherwise normal stroma of a carcinoma
  • There is a lack of criteria to differentiate squamous cell carcinoma with sarcomatoid differentiation from cutaneous carcinosarcoma
  • Management of cutaneous carcinosarcoma depends on the clinical and histologic features
    • The epithelial component correlates with metastasis
      • Basal cell carcinosarcoma = low-risk (2%)
      • Squamous carcinosarcoma and adnexal carcinosarcoma = (12-50%)
    • Tumor size, recent growth, metastases, and tumor chronicity may also affect management but are limited in number for definitive recommendations

Memorable Tweets:

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Until next month #dermpathJC, stay safe!

#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)

 

Article Abstract:

Angiosarcoma, one of the least common sarcomas, has become increasingly important because of its association with radiation therapy, especially for breast cancer. Most are sporadic, presenting as cutaneous tumors in the scalp/face of elderly patients. However, angiosarcoma has a wide anatomic distribution including soft tissue, visceral organ, and osseous locations. Predisposing conditions include environmental exposures to chemical or radioactive sources. Radiation-associated angiosarcoma typically presents as a cutaneous tumor several years posttherapy. The latency for radiation-associated mammary angiosarcoma is relatively short, sometimes less than 3 years. Atypical vascular lesion refers to a small, usually lymphatic-type vascular proliferation in radiated skin. Although most atypical vascular lesions pursue a benign course, they recur and very rarely progress to angiosarcoma. Distinguishing this lesion from well-differentiated angiosarcoma in a biopsy can be challenging, especially because areas indistinguishable from atypical vascular lesion are found adjacent to angiosarcoma. Recently, vascular-type atypical vascular lesion, which resembles hemangioma, has been described, thus expanding the definition of this entity.

 

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