#dermpathJC September 2020 summary

#dermpathJC September 2020:

Thursday, September 24th, 9 pm EST

Article Discussed: Pityriasis Lichenoides: a large histopathological case series with a focus on adnexotropism

Authors: Menzinger, Sébastien MD, Frassati-Biaggi, Annonciade MD, Leclerc-Mercier, Stéphanie MD, Bodemer, Christine MD, PhD, Molina, Thierry Jo MD, PhD, Fraitag, Sylvie MD

Temporary free access courtesy of American Journal of Dermatopathology: https://doi.org/10.1111/cup.13585

Summary prepared by: Riddhish Sheth, MD (@RShethMD)

Journal Club Summary:

Pityriases lichenoides (PL) is a rare skin disorder, the acute form of which is predominantly seen in children and young adults (PLEVA – pityriasis lichenoides et varioliformis acuta) and a milder, more chronic form (PLC – pityriasis lichenoies chronica), more often seen in adults. There is also a severe form known as febrile ulceronecrotic Mucha-Habermann disease. 

PLEVA histologically presents with epidermal hyperplasia with parakeratosis and neutrophils in the stratum corneum, dyskeratotic keratinocytes, interface dermatitis, lymphocytic exocytosis, dermal perivascular lymphocytic infiltrate, and red blood cell (RBC) extravasation.  PLC is described to have much milder changes.  There are cases where the histological features are incomplete or lack specificity which can lead to misdiagnosis of a lymphoproliferative disorder such as Lymphomatoid Papulosis (LyP).

71 cases were investigated in this case series. The authors noticed that vacuolated, necrotic keratinocytes were present in all cases, superficial and deep lymphocytic infiltration was present in 99% of cases, and adnexal lymphocytic infiltration was present in 97% of cases.  They noted that the inflammatory cells were mostly lymphocytes, neutrophils were only present in cases with ulceration of the superficial dermis, and that there were no eosinophils histologically identified in any of the study’s cases.  The authors also noted that 83% of cases showed perivascular or intraepidermal RBCs, and that 42% of cases had pallor of the upper part of the epidermis.  The authors alluded to Dr. Ackerman and his description of Pityriasis Lichenoides which included the superficial epidermal pallor but stated that this sign was not always easy for them to evaluate because it may be technique dependent.    

Immunohistochemical (IHC) studies were also performed on 11 cases at random and there was no IHC staining profile pattern which they found that would be reliable to aid in the diagnosis of the Pityriasis Lichenoides.

To go back to the adnexotropism mentioned earlier, the authors conclude that the superficial and deep dermal lymphocytic infiltrate is arranged in a periadnexal manner and it manifests as a “T-shaped” infiltrate which can be a low power clue in the diagnosis of Pityriasis Lichenoides.  They compared this low power pattern of the lymphocytic infiltrate to Vachellia tortilis, an African thorn acacia tree. This was seen in 97% of the cases in this series. 

Vasculitis or eosinophilic infiltrates are not a feature of Pityriasis Lichenoides.  Furthermore, in this case series, there were no histologic differences present between the specimens of adults and children.

Memorable Tweets:

Until next month #dermpathJC, stay safe and stay curious!

#dermpathJC August 2020 summary

#dermpathJC August 2020:

Thursday, August 27th, 9 pm EST

Article Discussed: Diffuse dermal angiomatosis associated with calciphylaxis: A 5‐year retrospective institutional review

Authors: Heather M. O’Connor, Qiong Wu, Steven D. Lauzon, Jessica A. Forcucci

Temporary free access courtesy of Journal of Cutaneous Pathology: https://doi.org/10.1111/cup.13585

Summary prepared by: Stanton Miller, MD (@StanMiller17)

Editor: Silvija P. Gottesman, MD (@SGottesmanMD)

Journal Club Summary:

Diffuse dermal angiomatosis (DDA) is a rare cutaneous vascular disorder, which was first reported by Krell et al. in 1994. It presents with violaceous plaques on the lower legs or affects pendulous breasts and it frequently ulcerates. Contributing factors are smoking, anticardiolipin antibodies and atherosclerosis. Associated conditions are cutis marmorata telangiectatica congenita and calciphylaxis, the latter being an inspiration for the study.

Histologic findings of Diffuse dermal angiomatosis show a vascular proliferation in the superficial and reticular dermis devoid of atypia and significant amount of inflammation. Vascular immunohistochemical markers can be used to highlight the extent of the proliferation.

  • The aim of the study was to investigate any association between calciphylaxis and diffuse dermal angiomatosis (DDA). There are some theories that DDA is a reactive vascular proliferation secondary to local ischemia and local production of vascular endothelial growth factor.
  • Calciphylaxis is associated with end-stage renal disease (elevated levels of calcium and phosphate). Patients with non-uremic calciphylaxis usually have either obesity, liver disease, hypercoagulability, use of warfarin or systemic steroids or autoimmune diseases. Histologically, deposition of calcium within small vessel walls of the subcutis is seen.
  • The authors noticed that some calciphylaxis biopsies have evidence of DDA in the overlying dermis and that it can be used as a helpful clue to dissect deeper in the fat and look for any evidence of small vessel obstruction by calcium.
  • The study showed statistically significant relationship between DDA and African-American race and Chronic Heart Failure. This is newly reported information in the literature. Patients with calciphylaxis and CHF had 33.2 times the odds of having associated DDA in their biopsies compared to those without CHF, and African-Americans with calciphylaxis had 22.2 times the odds of having associated DDA in their biopsies as compared to Caucasians.
  • End-stage renal failure, diabetes mellitus, immunosuppressive or hypercoagulable states, arrhythmias, Body Mass Index, hypertension, coronary artery disease, age, duration of calciphylaxis symptoms, and gender were NOT found to have statistically significant associations.

Memorable tweets:

  • There is a histologic distinction between DDA and Reactive angioendotheliomatosis and whenever possible the correct entity should be used in signout.
  • Communication between the pathologist and the clinician remains of paramount importance.

Take home point:

  • While Diffuse dermal angiomatosis has been seen in some cases of calciphylaxis, the most common scenario among the dermatopathologists have been of a benign vascular proliferation involving pendulous breasts. Always consider clinical presentation and location when making the diagnosis.

Until next month #dermpathJC, stay safe!

#dermpathJC June 2020 summary

#dermpathJC June 2020:

Thursday, June 25th, 9 pm EST

Articles discussed:

#1: Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of 5 cases

  • Authors: Cynthia Magro, J. Justin Mulvey, David Berlin, Gerard Nuovo, Steven Salvatore, Joanna Harp, Amelia Baxter-Stoltzfus, Jeffrey Laurence

#2: Skin manifestations of COVID-19

  • Authors: Sarah Young, MD, Anthony P. Fernandez, MD, PhD

#3: Thrombotic occlusive vasculopathy in a skin biopsy from a livedoid lesion of a patient with COVID-19

  • Authors: M. Llamas-Velasco, P. Muñoz-Hernández, J. Lázaro-González, A. Reolid-Pérez, B. Abad-Santamaría, J. Fraga, E. Daudén-Tello

#4-1: Digitate Papulosquamous Eruption Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection/#4-2: Petechial Skin Rash Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

  • #4-1 Authors: Adrien Sanchez, Pierre Sohier, Sarah Benghanem, Anne-Sophie L’Honneur, Flore Rozenberg, Nicolas Dupin, Bethsabée Garel
  • #4-2 Authors: Borja Diaz-Guimaraens, MD, Miguel Dominguez-Santas, MD, Ana Suarez-Valle, MD, Cristina Pindado-Ortega, MD, Gerald Selda-Enriquez, MD, Sonia Bea-Ardebol, MD, Diego Fernandez-Nieto

#5: Chilblains in children in the setting of COVID-19 pandemic

  • Authors: David Andina MD, Lucero Noguera-Morel MD, Marta Bascuas-Arribas MD, Jara Gaitero-Tristán MD, Jose Antonio Alonso-Cadenas MD, Silvia Escalada-Pellitero MD, Ángela Hernández-Martín MD, Mercedes de la Torre-Espi MD, Isabel Colmenero MD, Antonio Torrelo MD

#6: Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases

  • This article was not discussed during journal club but is recently published and included in the below summary
  • Authors: Raffaele Gianotti, MD, Sebastiano Recalcati, MD, Fabrizio Fantini, MD, Cristina Riva, MD, Mario Milani MD, Emanuele Dainese, MD, and Francesca Boggio, MD

All articles are open access with freely accessible histologic images.

Summary prepared by: Suzy Bloomquist, MD (@BloomquistSuzy)

Article summary:

The June 2020 DermpathJC covered a variety of articles on a new topic relevant to the ongoing pandemic – COVID-19-related skin conditions, including the clinical presentations and varied histologic appearance of the eruptions. Articles on this topic are limited to case presentations and case series; however many dermatopathologists are beginning to see these lesions in their clinical practice, highlighting the importance of sharing our knowledge on these topics. The various articles present a spectrum of the possible histologic patterns present in skin lesions of COVID-19 positive (or suspected positive) cases. Participating dermatopathologists added to the discussion with their experience regarding similar cases.

Introduction:

  • Skin manifestations are well known in the setting of viral illnesses. Some authors have reported skin involvement more than 20% of COVID-19 positive patients.
  • We are at a relatively early stage in the description of skin lesions relating to COVID-19. Even at this early stage however it appears that COVID-19 may have unique skin manifestations when compared with other viral illnesses. Further study is needed to determine the true specificity of these skin lesions.
  • The picture of cutaneous manifestations of COVID-19 is complicated by the fact that many patients are severely ill and being treated with medications at the time of biopsy; some of the cutaneous lesions may overlap with drug adverse effects.
  • There are still relatively few articles detailing histologic descriptions of COVID-19-related skin lesions in patients seen in the outpatient setting and in hospitalized patients.

Summary of clinical presentations of COVID-19-related skin disease:

  • Highly variable among patients and a single patient may present with multiple simultaneous cutaneous lesions of varying morphologies.
  • Many presentations including:
    • Lesions that are more non-specific:
      • Exanthematous/morbilliform rash
      • Urticarial
      • Maculopapular
      • Petechial rash
      • Pityriasis-like digitate papulosquamous eruption
      • Erythema-multiforme like lesions
      • SDRIFE-like eruption
      • Others (a single patient exhibiting multiple different
    • Lesions that may be more specific/unique to COVID-19:
      • Acral perniosis/Chilblains (“COVID toes”) – despite the descriptor may be seen on fingers and toes, consists of acral erythemato-violaceous or purpuric macules with some cases showing dark ischemic areas with superficial blisters or swelling.
      • Livedoid/retiform purpuric/vasculopathic lesions – these seem to be seen more frequently in cases of severe illness/acute respiratory failure in our chosen articles.
      • Varicella-like vesicular eruptions

Summary of histologic descriptions of biopsied lesions:

  • Retiform purpuric/livedoid lesions: thrombogenic vasculopathy at all levels of biopsy (including deep dermis) seen in either (or both) arteries or veins, accompanied in some cases by extensive necrosis of epidermis and adnexal structures, interstitial and perivascular neutrophil or lymphocytic infiltrate, prominent leukocytoclasia (one study noted deposition of C5b-9 in vessels in these cases with biopsy of normal skin in these patients also showing this deposition)
  • Perniosis/chilblains lesions on acral skin (largest study is in children/adolescents):  vacuolar degeneration of basal layer and lymphocytic exocytosis, perivascular (in-some cases dense/sleeve-like) and perieccrine lymphocytic infiltrate (prevalence of cytotoxic CD8+ lymphocytes), lymphocytic vasculopathy, acrosyringium, eosinophils in eccrine glands, microthrombi in small dermal vessels, scattered necrotic keratinocytes in one case, acute edema and severe vascular damage in cases of large bulla
  • Vesicular eruptions: interface dermatitis with apoptotic keratinocytes (similar to findings in other viral exanthems).
  • Exanthematous and maculopapular (non-specific) lesions:
    • Summarization of findings: Dermal edema, dilated capillaries, prominent erythrocyte extravasation, lymphohistiocytic infiltrate which may be perivascular, dilated vessels
    • Few cases also showed: spongiosis, minimal vacuolar dermal-epidermal junction changes, erythrocyte extravasation, eosinophils, nests of intraepidermal Langerhans cells.
  • Other: acantholytic dermatitis resembling Grover disease (2 cases)

Short review of chilblains/pernio:

  • A cutaneous localized inflammatory reaction resulting from maladaptive vascular response to non-freezing cold. Classified as primary or secondary to underlying disease. None of the cases of chilblains in suspected COVID-19 patients had other potential etiologies for chilblains. Chilblains in these cases should not be confused with the more thrombotic/livedoid complications observed in severely ill patients with COVID-19 (described more thoroughly in articles 1,3).

What can we learn from the skin of COVID-19 patients to infer its effect on other organs?

  • It seems clear that SARS-CoV-2 travels rapidly through the vascular system via an unknown mechanism. Some theories behind this are activation of eosinophils leading to a prothrombotic state or activation of a mannose-binding lectin pathway via glycoprotein binding and direct interaction with endothelium.

Additional points:

  • Deposition of C5b-9 was seen within dermal capillaries of even normal appearing skin of suspected COVID-19 positive patients in one study.
  • Article #2 highlighted that medications being used to treat COVID-19 also have cutaneous adverse reactions.
  • Little is known regarding the clinical value of recognition of cutaneous manifestations – for example, are there early cutaneous signs that may suggest a COVID-19 infection?
  • RT-PCR was performed on fresh skin in study #4 and was negative for SARS-CoV-2
  • The patient in article #4 had resolution of their rash within one week although the patient subsequently died of COVID-19-related illness.
  • In article #5, all adolescent/pediatric patients with chilblains had an excellent outcome without complications or severe disease manifestations with symptoms beginning to fade after 7-10 days.

A very important caveat:

  • Not all of the lesions described in these articles were in patients confirmed to have COVID-19, many were suspected cases. In study #5, while in the majority of cases (59%) a history of close contact with a COVID-19 symptomatic adult was noted, only 1 of 19 tested patients was PCR positive (however the study notes that PCR is positive in only 11.2% of children requiring hospital admission for suspected COVID-19).

In sum, there’s much to be learned about COVID19 #dermpath. We are grateful for open communications between dermatologists and pathologists, as clinicopathologic correlation is of paramount importance during these times.

Until our next journal club, be well and stay safe,

Sincerely,

DermpathJC

#dermpathJC May 2020 summary

#dermpathJC May 2020:

Thursday, May 28th, 9 pm EST

Article discussed: Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated

Authors: Juan C. Tardío, Fernando Pinedo, José A. Aramburu, Dolores Suárez-Massa, Ana Pampín, Luis Requena and Carlos Santonja

Temporary open access courtesy of Journal of Cutaneous Pathology: https://doi.org/10.1111/cup.12603

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

Article Summary:

Pleomorphic dermal sarcoma (PDS) is a rare neoplasm similar to atypical fibroxanthoma, but has fetaures of tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Metastatic risk is less than 5%, but ultimately very rare and more studies are needed to ascertain exact risk. The neoplasm fails to show any staining for cytokeratins, S100 protein, desmin or CD34.

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Journal Club Summary:

  • Atypical fibroxanthoma (AFX) is most commonly found on sun-exposed skin of the elderly, particularly the head
  • Histologically characterized by a mixture of spindle, epithelioid, and multinucleated giant cells with marked pleomorphism and many mitoses
  • Architecture may be fascicular, storiform, or haphazard
  • Immunohistochemistry is negative for cytokeratins (CK), S100, desmin, and CD34 while positive for vimentin, CD10, CD99 and variably CD68 and p53
  • 42, a marker of normal and neoplastic follicular dendritic cells (FDC), was shown to be positive in 50% of cases in this study and were negative for other FDC markers such as CD21 and CD23
    • Unfortunately, CNA.42 is positive in AFX, leiomyosarcomas, melanomas and carcinomas (unpublished observations by the authors)
  • According to the WHO, necrosis, invasion into deep subcutis or underlying fascia or skeletal muscle, lymphovascular invasion, or perineural invasion do not constitute a diagnosis of AFX
  • The name “pleomorphic dermal sarcoma” (PDS) has been proposed for such lesions, formally known as cutaneous malignant fibrous histiocytoma (MFH)
  • Confusion has ensued due to the lack of understanding about the true behavior of these lesions as well as some use of both terms as synonyms in the literature
  • Although controversy exists about using different terms for naming members of the same disease spectrum, the differences in clinical behavior between AFX and PDS merits an unambiguous message to the clinicians that is better guaranteed, in the authors opinion, distinguishing them by nomenclature
  • Clinical behavior is indolent with rare recurrence and even rarer metastasis (5% based on limited data and classification criteria)
  • Combining data from this study and a previous study by Miller et al, PDS seems to have a more aggressive clinical behavior, estimated to be 14% metastasis rate, including the skin, regional lymph nodes, and the lungs
  • At least 3 patients died from PDS (7%)
  • When metastasis has occurred, some cases infiltrate beyond the subcutis, contain necrosis, or contained no histopathologic or immunohistochemical information
  • A diagnosis of PDS should be reserved for tumors in sun-damaged skin of the elderly because they are extremely rare in non-sun-damaged skin, if they exist at all
  • TERT promoter mutations with an ultraviolet signature in 76% of PDS supports this view
  • Deletions in chromosomes 9p and 13p are seen in PDS at a similar frequency as AFX and undifferentiated pleomorphic sarcomas (UPS)
  • UPS shows H-ras and K-ras mutations (absent in AFX) and overall, more genetic alterations in complete genomic hybridization (CGH) studies
  • The authors retrospectively studied 18 PDS with emphasis on outcome and the differential diagnosis
  • Out of 12 previously classified PDS/cutaneous MFH and 112 AFX, the inclusion criteria for the series were as follows:
    • Spindle cell and/or pleomorphic dermal-based mesenchymal neoplasms without morphologic or immunohistochemical features diagnostic of any distinct entity
    • Lack of CK, S100 protein, desmin and CD34 expression
    • Invasion of at least the deep subcutis and/or tumor necrosis and/or vascular or perineural infiltration
  • 9 of the 12 PDS were excluded because primary subcutaneous sarcoma infiltration into the dermis could not be ruled out and expression of one or more of the above IHC
  • 15 of the 112 AFX cases were reclassified as PDS making a total of 18 PDS
  • M:F ratio was 1:1 (in contrast to previously reported male predominance)
  • Mean age was 81
  • Patients either had prior trauma or carcinomas in the same vicinity or immunosuppression due to rheumatoid arthritis, renal disease, or their age
  • Clinically they were described as either plaques or tumors, 10 of which were ulcerated
  • Mean size was 22mm with a range from 7-70mm
  • 13 cases showed an asymmetric silhouette and 15 cases showed an infiltrative border
  • Grenz zone, epidermal collarette and epidermal connection were absent in all cases
  • Except in cases with a conventional carcinomatous, melanocytic or sarcomatous component, sarcomatoid carcinoma, melanoma, leiomyosarcoma and angiosarcoma are mainly differentiated from PDS by their immunohistochemical (IHC) features
  • Sarcomatoid carcinoma will stain for cytokeratins, especially high molecular weight, and also p63 and EMA but can also be seen in PDS which makes them less useful
  • There will usually be numerous S100+ dendritic cells in PDS but never the neoplastic cells which helps differentiate PDS from melanoma, which will also likely have a conventional or in situ component
  • Leiomyosarcoma will have desmin and smooth muscle histologic features with marginated fascicles and characteristic elongated blunt-ended nuclei with fibrillary cytoplasm
  • Angiosarcoma has a similar site predilection to PDS, hemorrhage, and is positive for CD31, but is also positive for CD34 and ERG as well as a different clinical appearance with large ill-defined bluish, bruise-like patches that evolve into elevated plaques
  • Dermatofibrosarcoma protuberans (DFSP) is more common in younger patients on the trunk or proximal extremities and has a lace-like pattern that can mimic PDS along with CD34 positivity, however, DFSP has uniform spindle cells arranged in a monotonous storiform pattern somewhere within the lesion, even if there are MFH areas with loss of CD34, that will aid in the diagnosis of DFSP
  • Atypical and cellular dermal fibrous histiocytomas can have spindle to pleomorphic areas that may resemble PDS with similar lack of specific IHC, but usually present on the extremities of young to middle-aged adults with a Grenz zone and peripheral collagen entrapment that is limited to the dermis or, at most, the superficial subcutis
  • If PDS contains myxoid stroma, these must be distinguished from myxofibrosarcoma which differ in that they are often on the extremities, have a multinodular growth patter, broad spectrum of celluarity to stroma ratio, characteristic curvilinear thin-walled vessels and pseudolipoblasts.

Memorable tweets:

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Until next month #dermpathJC, stay safe!

#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)

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:

Untitled

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

 

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We are always here for you and your dermatopathology learning,

 

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#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!

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