#dermpathJC December 2021 summary

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#dermpathJC December 2021 summary

Thursday, December 9th, 9pm EST

Article discussed: Secondary skin involvement in classic Hodgkin lymphoma: Results of an international collaborative cutaneous lymphoma working group study of 25 patients. 

Authors: Gru, A., Bacchi, C. E., Pulitzer, M., Bhagat, G., Kempf, W., Robson, A., Plaza, J. A., Pincus, L., Raghavan, S., Xu, M., Vencato da Silva, T., Salavaggione, A. L., Subtil, A., & Battistella, M. 

Temporary free access courtesy of The Journal of Cutaneous Pathology: https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.14077

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

Journal Club Summary:

Overview:

  • While Hodgkin lymphoma (HL) is a fairly common B cell lymphoma overall in the US (approx. 9000 new cases per year); it is exceedingly RARE in the skin and when present is ALWAYS considered to be a secondary involvement of systemic HL. Simply put, the concept of primary cutaneous HL no longer exists.
  • Many previously reported examples of so-called primary cutaneous HL are now considered to be most likely cases of misdiagnosed lymphomatoid papulomatosis and cutaneous anaplastic large-cell lymphoma which both have overlapping histomorphology and immunophenotypic features with classic HL.
  • Possible mechanisms of skin involvement: “hematogenous dissemination, direct extension from involved lymph nodes, and retrograde lymphatic spread from proximally involved lymph nodes”
  • Implications of skin involvement: usually means the patient has stage IV disease (unless locoregional spread from nearby lymph node)

Tips:

  • Clinical presentation:
    • In this series:
      • 84% with cutaneous involvement by HL had stage IV disease
      • 67% showed skin lesions involving HL relapse
      • 28% of skin lesions present at time of diagnosis
      • 56% presented with solitary skin nodule (ulcerated lesion in 25%)
  • cd30
  • Histopathology:
    • Mixture of inflammatory cells, spares epidermis
    • Large RS cells may be difficult to find
    • +/- fibrotic bands (nodular sclerosis subtype)
    • Commonly present in the subcutaneous tissue, one case of “panniculitic” involvement
  • Useful IHC:
    • Classic HL: CD30+, CD15+ (usually although some exceptions), PAX-5 weak/dim
      • Negative: CD20 (or weak/focal in few), CD45
      • +/- MUM-1 (non-specific)
      • EBER may be positive
      • CD3+ T cells in background

Differential diagnosis with accompanying immunohistochemistry:

  • In more detail below:
      • Lymphomatoid papulomatosis (LyP):
        • Lacks classic RS cells, PAX-5 (-)
      • Cutaneous anaplastic large cell lymphoma (C-ALCL):
        • Shows dense diffuse infiltrate of the large atypical cells, cells have hallmark appearance, PAX-5 (-)
      • EBV+ mucocutaneous ulcer:
        • Clinical presentation different: around mouth or other mucosal surfaces, patients immunosuppressed and with shallow ulcers
        • NEED history as IHC pattern is very similar
      • EBV+ diffuse large B-cell lymphoma:
        • Cell types: mixture of centroblasts, immunoblasts, pleomorphic cells, RS-like cells, variable lymphocytes and histiocytes
        • Solid sheets of EBV+ cells
        • Strong PAX-5
      • Large B-cell lymphoma, unclassifiable with intermediate features between CHL and diffuse large B-cell lymphoma (gray zone lymphoma):
        • Strong expression of at least one B cell marker (CD20, CD79a, CD15)
      • Post-transplant lymphoproliferative disorders (PTLD):
        • Rarely CHL-like morphology, especially after solid organ transplant
        • Clinical history key

Helpful images:

Figure 1 from paper: Classic HL, nodular sclerosis type – dense dermal lymphocytic infiltrate sparing the epidermis, vague nodular pattern, classic RS cells seen with background mixed inflammatory infiltrate.

Figure 4 from paper: Classic HL, nodular sclerosis type (note nodularity plus bands of fibrosis) IHC staining pattern: note numerous CD3+ T cells in background (neoplastic cells negative). CD30+ (strong, diffuse), PAX-5 is dim in neoplastic cells contrasted to strong staining in background reactive B cells.

Figure 5 from paper: Classic HL, mixed cellularity type. Mixture of cells, no fibrosis, epidermis spared. Note mummified cells. Only rare conventional RS cells.

By popular demand, Dr Cha (@sunpungi) and Dr Gottesman (@SGottesmanMD) prepared a follow up YouTube video Q&A session with Dr Alejandro Gru (@alegru18), available at the embedded video link below:

Memorable tweets:

Hope you enjoyed this #dermpathJC. See you soon!

#dermpathJC July 2021 summary

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#dermpathJC July 2021

Thursday, July 29th, 9pm EST

Article discussed: Lichenoid dermatoses with pseudomelanocytic nests vs inflamed melanoma in situ: A comparative study

Authors: Gauri Panse, MD, Jennifer M. McNiff, MD

Temporary free access courtesy of The Journal of Cutaneous Pathology: https://onlinelibrary.wiley.com/doi/10.1111/cup.13945

Summary prepared by: Haneen Salah, MD (@Hansalah)

Journal Club Summary:

Introduction:

  • Pseudomelanocytic nests (pseudonests) were first defined as group of Melan-A positive cells in non-melanocytic lesions. They have been seen in various dermatitides, such as lichen planus, lupus erythematosus, fixed drug eruption and phototoxic eruptions. They have also been reported in solitary lesions such as lichen planus-like keratosis and basal cell carcinoma with regression. Pseudomelanocytic nests arising in lichenoid dermatoses are considered a diagnostic pitfall for regressed melanoma in situ (MIS).
  • This paper discusses histopathologic features and important morphological clues that help dermatopathologists in differentiating this benign entity from inflamed melanoma in situ (MIS). Clinicopathological correlation is important to achieve the accuracy of the final diagnosis, particularly in challenging cases.

Summary of current study methodology and results:

  • The authors performed a retrospective review of the dermatopatholgy archive at their institutions. Ten biopsy specimens with pseudomelanocytic nests within lichenoid dermatoses were identified, and twenty cases of inflamed (lichenoid) or regressing MIS were retrieved for comparison.
  • Here is an example of a patient with cutaneous eruption compatible with graft vs host disease, and histopathologic findings that included pseudomelanocytic nests.
  • Cases with pseudomelanocytic nests were either a pigmented rash (n = 6) or a discrete non-melanocytic lesion, such as lichenoid keratosis (n = 4). All the cases with pseudomelanocytic nests exhibited nests of microphthalmia-associated transcription factor (MITF)-positive cells at the dermo-epidermal junction (DEJ), interface changes, and lichenoid inflammation, and did not display pagetoid scatter, confluence of solitary melanocytes at the DEJ and significant cytologic atypia. All cases of inflamed MIS showed confluence of single melanocytes at the DEJ with cytologic atypia (P < 0.001) and 18/20 cases showed pagetoid scatter of melanocytes (P = 0.001).
  • The comparative histopathologic features between patients with pseudomelanocytic nests and inflamed melanoma in situ are shown in Table 2.

Discussion points:

  • The presence of pseudomelanocytic nests in sun-damaged skin causes diagnostic challenge for dermatologists and dermatopathologits, where atypical junctional melanocytic lesions are more likely to be present.
  • The morphological and immunohistochemical overlap between pseudomelanocytic nests and atyical nests of melanocytes in inflamed MIS makes clinical correlation vital to rule out an atypical junctional melanocytic proliferation. The immunohistochemical staining of pseudomelanocytic nests with nuclear markers such as SOX10 and MITF adds to the diagnostic difficulty in differentiating this phenomenon from MIS. The pseudonests are composed of degenrated melanocytes, keratinocytes and macrophages. They have also been reported to stain with Mart-1/Melan-A.
  • This study is the largest series showing that pseudomelanocytic nests lack morphological features like pagetoid scatter and confluence of solitary atypical melanocytes at the DEJ, while these features occur in most cases of inflamed melanoma in situ. These two features should help dermatopathologists in differentiating those two entities morphologically.
  • Below is a melanoma in situ with lichenoid inflammation for comparison:

Conclusion and future directions:

  • One limitation of this study is that the control group included unequivocal cases of inflamed MIS only, while cases where a definitive diagnosis of MIS was not rendered, were excluded.
  • The authors of this study suggest that the presence of pagetoid scatter and confluence of atypical solitary melanocytes at the DEJ may be a useful morphologic clue to differentiate pseudomelanocytic nests from inflamed MIS in diagnostically challenging cases.
  • Although immunohistochemical findings require careful interpretation, and a thorough histopathologic examination, clinical correlation is important to eliminate the possibility of melanoma in situ with lichenoid inflammation in puzzling cases.

Memorable Tweets:

  • Please find the memorable tweets and important figures from the paper attached.

Looking forward to the next #dermpathJC. Stay well my friends!

#dermpathJC March 2021 summary

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#dermpathJC March 2021:

Thursday, March 25th, 9pm EST

Article discussed: Vulvar dermatoses: a histopathologic review and classification of 183 cases

Authors: May P. Chan, MD, and Mary Jane Zimarowski, MD

Temporary free access courtesy of: The Journal of Cutaneous Pathology, https://onlinelibrary.wiley.com/doi/10.1111/cup.12541

Summary prepared by: Haneen Salah, MD (@Hansalah)

Journal Club Summary:

Introduction:

  • Vulvar dermatoses often pose challenges in classification due to histopathologic overlap. This study documents a single institution experience in diagnosis of vulvar dermatoses, with focus on the frequencies of these conditions as well as detailing subtle histopathologic differences that can aid in either making a diagnosis or narrowing down a differential.
  • The International Society for the Study of Vulvovaginal Disease (ISSVD) has established a classification system to better aid the diagnosis and to unify terminology used by both dermatopathologists and gynecologic pathologists.

Summary of current study methodology and results:

  • A total of 188 vulvar biopsies signed out between 2006 and 2010 were reviewed. Five of the cases were excluded due to infectious causes. The remaining 183 cases were analyzed. The average age of the patients was 53.6 years.
  • Lichen sclerosus (LS) was the most common diagnosed vulvar dermatosis (38.8%). Next most common diagnosis was lichen simplex chronicus (LSC) at 29% and eczematous dermatitis (23%), subtyped into allergic contact dermatitis, irritant contact dermatitis and eczema nos. Zoon’s vulvitis was rarely diagnosed (15%).

Discussion points:

  • Keeping a broad differential diagnosis is crucial. While there are some dermatologic conditions limited to vulvar skin, there are many dermatoses that can be seen there and are not restricted to the genitalia.
  • Commonly a multifactorial condition affects the vulvar skin. The most common scenario is LSC superimposed on LS or eczematous dermatitis and even lichen planus. Diagnosing the specimen with LSC should not stop there and careful examination of the underlying dermis is recommended to investigate a primary dermatosis with overlying LSC.
  • LS was the most common diagnosis in this cohort of patients, which could be as a result of clinicians having a lower threshold to biopsy patients with LS.
  • The major diagnoses with histopathologic features:
  • Lichen sclerosus (LS): Lichenoid interface dermatitis is a notable early change. Thickened basement membrane can be seen and highlighted with a PAS stain. Wiry fibrosis with lymphocyte entrapment seen at the inferior edge of the subepithelial sclerosis is a useful feature to diagnose LS.  This study noted that almost half of the cases had scattered eosinophils, and the presence of eosinophils should not preclude a diagnosis of LS.
  • Lichen simplex chronicus (LSC): Squamous mucosa and skin affected by LSC may appear quite similar. While vertical fibrosis may be commonsly seen in skin affected by LSC elsewhere, in the vulva, the authors’ experience for vulvar LSC is presence of prominent fibroblasts and zones of pale epithelium. These pale cells resemble “pagetoid dyskeratosis,” and are thought to be clones of keratinocytes that proliferate as a result of chronic friction.
  • Eczematous (spongiotic) dermatitis: Presence of spongiosis, presence of intraepithelial neutrophils and necrotic keratinocytes were clues for Irritant Contact Dermatitis (ICD) and presence of intraepithelial eosinophils (eosinophilic spongiosis) was a clue for Allergic Contact Dermatitis (ACD). Some cases with overlapping features were commonly signed out as eczema NOS.
  • Zoon’s vulvitis (ZV): Typical findings include band-like plasma cell infiltrate, often an eroded surface, intraepithelial neutrophils, extravasated erythrocytes and hemosiderin deposition. Considerable difficulty in diagnosis of Zoon’s vulvitis exists particularly when the classic features are not present. Some report presence of “lozenge-shaped” keratinocytes and fibrosis. The authors in this study report a new clue for the diagnosis of Zoon’s vulvitis; basal keratinocytic crowding which was seen in 86.7% of the ZV cases. This feature may be helpful in differentiating from early LS.
  • Lichen planus (LP): This study reported lower number of LP cases and a reliable feature to differentiate LP from LS was not identified. However a thickened basement membrane highlighted with a PAS stain and decreased elastic fibers highlighted with an elastic EVG stain may help diagnosis of early LS over LP.
  • Infections: Most commonly overlooked infections in the vulva were erythrasma caused by C. minutissimum and herpetic infection. Careful examination of all deeper sections is advised.

For additional helpful info check out our YouTube Q&A Session with Dr Chan, Dr Cha (@sunpungi) and Dr Gottesman (@SGottesmanMD):

Memorable Tweets:

Thanks again for another amazing #dermpathJC, see you soon!

#dermpathJC February 2021 summary

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#dermpathJC February 2021:

Thursday, February 25th, 9pm EST

Article discussed:  Erythema Migrans and Interface Changes: More Than a Fortuitous Association

Authors: Tekin, Burak MD; Song, Yali MD; DiCostanzo, Damian MD; Lee, Bonnie A. MD

Temporary free access courtesy of The American Journal of Dermatopathology: https://journals.lww.com/amjdermatopathology/pages/articleviewer.aspx?year=2020&issue=10000&article=00004&type=Fulltext

Summary prepared by: Shaymaa Ashi, MD (@shaymaloh)

Journal Club Summary:

Introduction:

  • This article reviewed the histopathologic characteristic of erythema chronicum migrans (ECM), with emphasis on the classical features and observation of new patterns.
  • ECM represents the cutaneous manifestation of early Lyme disease. It typically presents with polycyclic targetoid rash with erythematous border and central clearing. Fully developed lesions usually measure >5 cm.  It is usually localized; but can be disseminated (25%).
  • Diagnosis is made based on clinical findings (characteristic clinical lesions, history of tick bite) and response to treatment. Serology has low sensitivity in early Lyme disease.  PCR can be used for confirmation.
  • Biopsy is warranted when the clinical presentation is atypical (vesicular, bullous, or hemorrhagic/purpuric rash, no history of tick bite) to confirm ECM and exclude other entities in the differential diagnosis (viral exanthems, arthropod bite reaction, erythema nodosum, drug eruption, gyrate erythema, dermatitis, and tinea).
  • Classic histopathologic features are superficial to deep perivascular inflammatory infiltrate, mainly of lymphocytes, associated with plasma cells and eosinophils.
  • Some studies state that variations in histomorphology can occur, including interface dermatitis, spongiosis, necrotic keratinocytes, absence of plasma cells.

Summary of current study methodology and results:

  • The aim of this study is to detect the frequency of variable histopathologic findings in ECM lesions to increase the diagnostic sensitivity of biopsy, usually performed to establish the diagnosis in cases with atypical clinical presentations.
  • Two dermatopathologists evaluated biopsies from a cohort of 14 cases with clinically and/or serologically confirmed Lyme disease from the archives of 2 institutions located in Lyme disease endemic area (Ackerman Academy of Dermatopathology and Dermpath Diagnostics in New York). The most prominent histopathological changes detected are summarized as follows:
  • All 14 cases demonstrated a superficial perivascular lymphocytic infiltrate.
    • 5/14 cases (36%) did not have any additional changes
    • 11/14 cases (64%) showed additional interstitial and/or deep perivascular lymphocytic infiltrate
    • The density of the infiltrate was variable (sparse to markedly dense). Nodular or pseudolymphomatous infiltrates were not identified as opposed to other studies
    • 12/14 cases (86%) showed interface changes, ranging from focal to diffuse
    • 2/14 cases (14%) showed necrotic keratinocytes
    • 2/14 cases (14%) showed mild spongiosis
    • 7/14 cases (50%) showed eosinophils
    • 10/14 case (71%) showed plasma cells
    • 3/14 cases (21%) showed extravasated RBCs
A-C Focal interface dermatitis, papillary dermal edema and extravasated RBCs. D: lymphocyte exocytosis to basal layer. Arrows in A-D: elongated squiggly lymphocytes

Summary of literature review:

  • Berger et al (1983): Some cases (24%) show lymphocytes blurring of the dermo-epidermal junction (44%) and extend to epidermis (21%)
  • de Koning (1983): Some cases have lymphocytes disrupting the dermo-epidermal junction and the basement membrane
  • Böer et al (2007): Vacuolar degeneration seen in 8/34 cases, lymphocytes seen in basal layer (15/34), and in suprabasal epidermal levels (7/34)
  • Wilson et al (2012): Interface/vacuolar change seen in 2/4 cases (50%)
  • Miraflor et al (2016): Interface change seen in 3/8 cases (38%)

Discussion points:

  • Interface dermatitis, focal to diffuse, with sparse perivascular lymphocytic infiltrates, is seen in a high percentage of ECM biopsies, and scrutiny is needed in examining the tissue to look for subtle/focal interface changes, to avoid missing ECM cases in the earlier phase when serology tends to be negative.
  • This study has higher percentage of ECM cases with interface dermatitis (86%) compared to the other studies mentioned in the literature review.  
  • More than 50% of the cases in this study had only focal interface changes.
  • The density of the dermal infiltrates is variable.
  • The center of early lesions has more eosinophils, while the periphery has more plasma cells. This study had comparable results to those of Miraflor et al study regarding plasma and eosinophils percentage, while Wilson et al indicated absence of plasma cells in his case cohort and Boer et al indicated plasma cells were unreliable criterion for ECM diagnosis.
  • A new observation in this study is that reactive lymphocytes seen in biopsies from infections are elongated and squiggly, correlating with findings of ultrastructural studies of reactive T lymphocytes.
  • The limitation of this study: retrospective study design, diagnosis was not uniformly confirmed in all cases by serology or PCR, site of biopsies (center versus periphery) was not indicated.
  • ECM can have variable histopathologic manifestations and should be included in the differential diagnosis of sparsely inflamed biopsies and those with subtle/focal interface dermatitis.

Memorable Tweets:

And now a SPECIAL interview with Dr Bonnie Lee (senior author of ECM paper) on the ASDP YouTube channel: Dr Silvija Gottesman and Dr Jisun Cha’s #DermpathJC​ Q&A session with Dr Bonnie Lee about the histologic findings of Erythema Chronicum Migrans, a characteristic cutaneous eruption that appears in the early stages on Lyme disease.

Until next month #dermpathJC, stay safe!

#dermpathJC January 2021 summary

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#dermpathJC January 2021:

Thursday, January 28th, 9pm EST

Article discussed: Histopathologic evaluation of nail lichen planus: A cross-sectional study

Authors: Geetali Kharghoria, MD, DNB, Chandra Grover MD, DNB, MNAMS, Sambit Nath Bhattacharya, MD, Sonal Sharma, MD

and

Editorial: The “frayed nail plate” and further detailed analysis of the histopathologic features of nail unit lichen planus from Dr Adam I. Rubin, MD

Temporary free access courtesy of the Journal of Cutaneous Pathology:

https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13783

https://doi.org/10.1111/cup.13845

Summary prepared by:  Parneet Dhaliwal, DO (@FollowPath)

Journal Club Summary:

INTRODUCTION

  • Nail involvement can be seen in up to 10% of patients with lichen planus (LP)
  • Fingernails are affected more often than toenails
  • Any part of the nail can be involved, but the nail matrix is characteristic of nail lichen planus (90% of cases) and can present as “longitudinal striations, thinning of nail plate, dorsal pterygium, or trachyonychia.”
  • The disease course progresses slowly but surely, and many patients develop scarring, anonychia, and pterygium formation.
  • Zaias first described histopathology of nail LP in 1970:
    • Hyperkeratosis
    • Hypergranulosis
    • Papillary dermis with band-like lymphocytic infiltrate
    • Basal layer degeneration
    • Colloid bodies
    • Pigment incontinence (melanophages)
  • Major and minor criteria of nail LP:

PATIENTS AND METHODS

  • 45 patients from Department of Dermatology and Venereology and Pathology at a teaching hospital in Dehli, India were recruited, consented, and screened
  • Nail biopsy of most representative site was preformed (nail bed vs nail matrix)
  • Major and minor criteria were applied to the biopsies

RESULTS

  • Patient population
    • N=45
    • Mean age: 36.91 +/- 18.27 years
    • M>F (male predominance 64%)
    • Mean disease duration: 29.07 +/ 25.85 months
  • Clinical LP presentations:
    • Oral mucosa LP – 51%
    • Genital involvement – 0%
    • Isolated nail LP – 29%
    • Generalized LP – 28.8%
    • Linear LP – 6.6%
    • Lichen planopilaris (cicatricial alopecia) involving the scalp – 6.6%
    • Palmoplantar LP – 2.2%
    • LP pigmentosus – 2.2%
  • Most common presenting symptom: brittleness or fragility – 40%
  • Nails involved: 8.13 +/ 4.94; Fingernails > Toenails
  • Most common nail plate changes: onychorrhexis (100%), longitudinal melanonychia (88.9%), onychoschizia (82.2%), thinning and distal splitting (62.2% and 48.9%)
  • Most common nail fold changes: ragged cuticle (91.1%), absent cuticle (11.1%), nail fold hyperpigmentation (11.1%)
  • Most common nail bed changes: erythema (88.9%), onycholysis (55.5%), subungual hyperkeratosis (46.7%)
  • Histopath:
    • Major criteria – 51.1%
      • Sawtooth acanthosis – 44.4%
      • Lymphocytic infiltrate – lichenoid band under the dermo-epidermal junction – 24.2%
    • Minor criteria
      • Most common: presence of granular layer in nail matrix and bed epithelium – 51.1%
      • Increased eosinophilia of nail bed keratinocytes – was not seen in any
    • Additional significant finding: “frayed nail plate” due to separation of individual orthokeratotic onychocytes from the nail plate – seen in 33.3% of cases – not previously reported in other studies (see image below)

Most memorable tweets and few pearls from the article’s discussion:

  • Mean age of nail involvement with LP was lower than previously stated – possibly related to increased awareness of cosmetic appearance of nails
  • Mucosal LP was the most common association with nail LP – Dr Rubin also accounts for this association in his nail clinic as well
  • Most common nail fold involvement: ragged cuticle – 95.5%

And now a SPECIAL TREAT for all of you, a SPECIAL interview with Dr Adam I. Rubin (@adamirubin) on the ASDP YouTube channel: Dr Jisun Cha and Dr Gottesman’s #DermpathJC Q&A session with Dr Adam Rubin about lichen planus of the nail unit. While much of the video focuses on the histopathologic features of nail lichen planus and its mimics, the last 15minutes of the discussion are focused on various treatment options for this disease.

Until next month #dermpathJC, stay safe!

#dermpathJC November/December 2020 summary

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#dermpathJC November/December 2020:

Thursday, December 10th, 9pm EST

Article Discussed: Concordance Analysis of the 23-Gene Expression Signature (myPath Melanoma) With Fluorescence In Situ Hybridization Assay and Single Nucleotide Polymorphism Array in the Analysis of Challenging Melanocytic Lesions: Results From an Academic Medical Center

Authors: Stephanie A. Castillo, MD, Anh K. Pham, MD, Alicia T. Dagrosa, MD, MBA, Shaofeng Yan, MD, PhD, Dorthea T. Barton, MD, Joel A. Lefferts, PhD, and Konstantinos Linos, MD

Temporary free access courtesy of The American Journal of Dermatopathology: DOI: 10.1097/DAD.0000000000001713

Summary prepared by: Anthony Wheeler, MD (@Pathosomes)

Journal Club Summary:

  • This article reviewed concordance between molecular tests used to assist in the diagnosis of challenging melanocytic lesions
  • Histology is the gold standard for diagnosing melanoma and other melanocytic lesions
  • At times the histologic interpretation of the specimen may be particularly challenging, thus it may be prudent to obtain molecular testing
  • The molecular tests that were assessed include fluorescence in situ hybridization (FISH), single nucleotide polymorphism (SNP) arrays, and 23-gene expression signature (GES)
  • FISH molecular testing uses specific DNA probes that can bind to a region of interest on a particular chromosome. There are various different DNA probes that can detect repetitive sequences, missing sequences, there are also whole chromosome probes, telomeres probes, chromosome breaks and fusion probes.
  • Chromosomal abnormalities due to copy number differences have been reported in melanoma, such as gains in 6p25 (RREB1) and gains in RREB1/Cep6, losses in 6q23 (MYB), gains in 11q13 (CCND1), gains in 8q24 (MYC), and mutations in 9q21 (CDKN2A) gene.
  • A CME article from the American Journal of Dermatopathology by Ferrara et al (doi: 10.1097/DAD.0000000000000380) summarizes that “melanoma commonly harbor gains at 6p, 7q, 17q, 20q, 4q, 8q, 1q, and 11q, whereas common deletions include 9p, 10, and 21q. In particular, 6p gain in melanoma was associated with an unfavorable prognosis.”
  • SNPs can be used to detect small copy number variations. They can be interpreted as normal if there is no deviation in the copy numbers, equivocal if there is low number of copy number aberrations and abnormal if there are multiple complex aberrations or if there are gains or losses in chromosomes 1, 6, 8, 9, and 11. To add, if 11p gain (HRAS) is the only abnormality detected in a specimen with spitzoid morphology, the authors share that this was deemed benign because this is an expected finding in some Spitz nevi.
  • The 23-GES utilizes qRT-PCR to detect expression of twenty three genes to help distinguish melanoma from melanocytic nevi. myPath® Melanoma is a 23-gene expression signature (GES) test and categorize lesions as benign, malignant, or indeterminate.
  • FISH, SNP, and GES have all been shown to aid in the diagnosis of challenging melanocytic lesions
  • The American Society of Dermatopathology Appropriate Use Criteria Task Force recognizes the use of FISH and SNP testing to assist in the diagnosis of challenging melanocytic lesions
  • The researchers utilized their experience with the GES assay to primarily investigate the degree of concordance between GES and FISH, as well as GES and SNP
  • The researchers utilized a single-institution retrospective analysis of 61 contiguous cases of challenging melanocytic lesions that required molecular analysis
  • The primary objective of the study was to determine the interest agreement between GES and FISH, and the interest agreement between GES and SNP arrays in the analysis of challenging melanocytic lesions
  • A secondary objective was to determine the combined test performance between the molecular tests that were utilized
  • The specimens that were included in the study were not metastatic, or re-excisions, and had at least two molecular tests
  • SNP array cases with a spitzoid histomorphology and a sole 11p gain abnormality were considered benign, due to the consistency of these findings being diagnostic of Spitz Nevi
  • Cases that underwent 23-GES (myPath® Melanoma) testing involved sending unstained slides and an hematoxylin and eosin (H&E) slide with the lesion marked to Myriad Genetics, where the specimen was assessed and proprietary scored
  • SNP analysis was performed at the researchers home institution by extracting DNA from a formalin fixed paraffin-embedded specimen, and utilizing the OncoScan FFPE Assay Kit (Affymetrix, Inc., Santa Clara, CA)
  • FISH analysis for many of the specimens was performed at the Mayo Clinic Laboratory utilizing a marked H&E slide to locate the lesion as a reference, to guide location for hybridization on the unstained slides using specific probes for melanoma. Two technologists analized a total of 50 interphase nuclei for each probe (25 nuclei each).
  • The overall percent agreement between GES and FISH was 50.9%, and the percent agreement between GES and SNP was 57.1%
  • Percent agreement was improved, when indeterminate/equivocal results were excluded, to 69.7% (for GES and FISH), to 77.8% (for GES and SNP).
  • The combined-test analysis supports the utilization of more than one molecular test to increase the odds of obtaining a successful test on challenging melanocytic lesions
  • Perhaps in the future an ideal concordance study can be done and include lesions that have had three different molecular tests

Memorable Tweets From The Interesting Discussion:  

Until next month #dermpathJC, stay safe!

#dermpathJC October 2020 summary

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#dermpathJC October 2020:

Thursday, October 29th, 9pm EST

Article Discussed: A review of CD30 expression in cutaneous neoplasms

Authors: Drs. Franziska Kampa and Christina Mitteldorf

Temporary free access courtesy of Journal of Cutaneous Pathology, link: https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.13894

Summary prepared by: Maryam Aghighi, MD (@maryam_aghighi)

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

Journal Club Summary:

  • The current article reviewed the literature for CD30 expression in lymphoproliferative disorders and solid tumors of the skin.
  • CD30 (Ki-1) is a transmembrane protein in the tumor necrosis factor receptor superfamily. It is expressed by Reed-Steinberg cells. The CD30 ligand (cytokine) is detected on activated lymphocytes, histiocytes and granulocytes.
  • CD30 is expressed mainly on Th2 cells, but there is some published data that Th0 and Th1 cells show CD30 expression. As for B-cells, CD30 is expressed in B-cell immunoblasts, found at the germinal center periphery.
  • CD30 is expressed in anaplastic large cell lymphoma (ALCL), Hodgkin lymphoma (HL), lymphomatoid papulosis (LyP), mycosis fungoides (MF), follicle center cell lymphoma (FCL) and Epstein-Barr virus (EBV)-associated lymphomas.
  • Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody, conjugated with monomethylauristatin, and used in the treatment of CD30+ HL, systemic ALCL, CD30 expressing peripheral T-cell lymphomas and CD30+ cutaneous T-cell lymphomas.
  • Treatment with BV has been effective in cutaneous T-cell lymphomas (CTCL) and diffuse large B-cell lymphoma (DLBCL) including in cases with low or absent CD30 expression.
  • In cutaneous lymphomas, the CD30 positivity threshold is under debate. Up to 40% of hematopathologists use a positive cut-off value of >20% CD30+ cells, while the response cutoff in BV clinical trials was >10% CD30+.
  • Cutaneous and folliculotropic MF patients with a higher dermal CD30 expression showed a more advanced stage at diagnosis, higher maximum stage, lower survival rate and poor prognosis. However, patients with high epidermal CD30 expression revealed higher survival rate.
  • Transformed MF (T-MF) is diagnosed if >25% large cells (>4x the size of a lymphocyte) are present. Dermal CD30 expression is related to a better prognosis in T-MF and absence of CD30 expression was associated with poorer prognosis. Interestingly, higher epidermal CD30 expression compared to dermal CD30 expression was associated with a poorer survival.
  • In other rare types of CTCLs, published literature to date of CD30 expression is as follows:
    • In pagetoid reticulosis (PR), more than 50% of the tumor cells were CD30+.
    • Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS) reported CD30 expression as follows:
      • One study showed low expression of CD30 (<5%) in most of their patients.
      • One study showed more than half the studied patients to have a CD30 expression of 25% or more.
      • In small-medium pleomorphic T-cell lymphoma (SMPTCL) CD30-positive expression was reported between <1% and 30%.
    • In cases of extranodal NK/T-cell-lymphoma (ENK/TCL), CD30 positivity has been seen and in one case reaching >80%.
    • Primary cutaneous gamma-delta T-cell lymphoma (pcGD-TCL), primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECTCL) and subcutaneous panniculitis-like T-cell Lymphoma (SPTL) reported CD30 expression (further reading recommended to explore the amount of CD30 expression in each of these distinct entities).
    • A single case of primary cutaneous acral CD8+ T-cell lymphoma (pcATCL) reported negative CD30 expression.
    • Adult T-cell leukemia/lymphoma (ATLL) reported positive CD30 expression but skin expression of CD30 positivity was not mentioned.
  • Observed CD30 expression in primary cutaneous B-cell lymphomas is as follows:
    • Primary cutaneous follicle center B-cell lymphomas with CD30 expression was seen in few patients and primary cutaneous marginal zone B-cell lymphoma showing CD30 positivity was seen in even fewer patients.
    • Four diffuse large B-cell lymphoma leg type patients reported negative CD30 staining.
  • EDV-positive mucocutaneous ulcer and EDV-associated lymphoproliferative disorders reported high CD30 expression.
  • Blastic plasmacytoid dendritic cell neoplasm – negative CD30 expression reported thus far.
  • Cutaneous mastocytosis had CD30 expression in 96.5% of cases (29 study patients).
  • Other notable neoplasms that also showed expression of CD30 were lymphadenomas. CD30 expression was reported in the the tumor microenvironment (TME) of BCC, SCC and keratoacanthomas.
  • There was no data reported regarding CD30 expression in Merkel cell carcinoma and only a couple of cases of atypical fibroxanthoma with reported CD30 expression.  

Memorable Tweets from the Journal Club Discussion:

Until next month #dermpathJC, stay safe!

#dermpathJC September 2020 summary

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#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

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#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!