#dermpathJC August 2019 summary

#dermpathJC August 2019:

Thursday, August 22nd, 9 pm EST

Article discussed: Is melanocyte density our last hope? Comparison of histologic features of photodamaged skin and melanoma in situ after staged surgical excision with concurrent scouting biopsies

Authors: Jodi Speiser, Joy Tao, Amanda Champlain, Lauren Moy, Monica Janeczek, Reeba Omman, Kumaran Mudaliar, Rebecca Tung

Temporary open access courtesy of Journal of Cutaneous Pathology at: https://doi.org/10.1111/cup.13462

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

 

Journal article summary:

Differentiating melanocytic hyperplasia (MH) on photodamaged skin from junctional lentiginous melanocytic proliferations (JLMP), early evolving melanoma in situ (MIS), or the periphery of a lesion of MIS on staged excision can be challenging. Although previous cross-sectional studies have elucidated important criteria for distinguishing MH on photodamaged skin from more concerning lesions, this study highlights a technique to treat JLMP and MIS with staged mapped excision and baseline scouting biopsies of adjacent nonlesional photodamaged skin to assist in determination of surgical margin clearance. Additionally, we compare the lesional and photodamaged control biopsies from the same patient to evaluate relevant histologic criteria that may be used to distinguish MH in photodamaged skin from JLMP/MIS, while minimizing confounding factors. There was a statistically significant difference (P ≤ 0.05) found for melanocyte density, irregular melanocyte distribution, melanocyte clustering, follicular infundibulum involvement, and nesting. However, criteria such as nesting, epithelioid cells and melanocyte clustering were seen in both photodamaged skin and MIS. These findings underscore the fact that histologic features of photodamaged skin can overlap with the histopathological features of MIS. Of all of the criteria evaluated, melanocytic density was the most objective histologic criterion and did not show overlap between the sun-damaged and JLMP/MIS groups.

FIGURE 1 Clinical image showing clinical lentiginous lesion (after Wood’s lamp illumination) along with markings for scouting biopsies. FIGURE 2 Clinical image showing an additional peripheral surgical margin drawn approximately 5 mm away from the delineated clinical lesion. The margins are labeled like a clock face for orientation with the numbers 3, 6, 9, and 12. Two 3 mm scouting punch biopsies were taken at least 2 cm away from the original lesion.

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Journal Club Summary:

  • Overlap between melanocytic hyperplasia (MH) and junctional lentiginous melanocytic proliferations (JLMP) and melanoma in situ (MIS) can be a significant diagnostic dilemma.
  • Further complication arises from variability in diagnostic criteria among pathologists leading to over and under-diagnosis.
  • Lentigo maligna (LM) is a subtype of MIS that grows on chronically photodamaged skin, predominantly on the head and neck.
  • In an established lesion, LM is histologically defined as a junctional proliferation of confluent single cells and nests of large atypical melanocytes, which may demonstrate focal upward pagetoid spread.
  • In contrast, the background nonlesional photodamaged skin displays melanocytic hyperplasia (MH) and cytologic enlargement and mild pleomorphism.
  • This study used formalin-fixed paraffin-embedded staged mapped excision from a “slow Mohs” procedure in tandem with baseline scouting biopsies of adjacent non-lesional photodamaged skin to assist in determination of surgical margin clearance.
  • The advantages for this technique include entire margin assessment and the need for specific additional excision, as well as better cosmetic outcomes.
  • The lesional and photodamaged control biopsies from the same patient were compared using nuclear IHC stains to assess clinically relevant histologic criteria that may be used to distinguish photodamaged skin from JLMP and MIS.
  • Inclusion criteria included patients (a) with a previous biopsy-confirmed JLMP or MIS (lentigo maligna or superficial spreading subtypes) in a cosmetically or surgically challenging location that was available for review, (b) whose biopsy included an IHC stain for MiTF or Sox-10 and (c) who were eligible for staged excision.
  • Exclusion criteria included patients with previous biopsies that were unavailable for review or without IHC stain for MiTF or Sox-10, palpable areas within the lesion, cervical lymphadenopathy, an invasive component on initial biopsy or any contraindication for staged excision
  • The combination of histologic and clinical features aid in differentiating benign melanocytic junctional proliferations from lesions described as AJMP include more advanced patient age, presence of background sun damage, lentiginous melanocyte clustering, increased melanocytic density, lack of upward spread, lack of definitive confluence (>3 consecutive melanocytes), and no/minimal nests.
  • The clinical management of each entity has been highly debated.
  • The NIH recommends a 5 mm margin on surgical excisions but has been had mixed success on proven adequacy.
  • Staged excisions generally have high cure rates, with two studies reporting recurrence rates of 1.7% and 2.2%, respectively, although utilizing less specific IHC stains as this study.
  • Creation of specific criteria and definitions of LM, JLMP/MIS have been revised over the decades, originating from Ackerman et al who were the first to propose a set of 12 criteria which included:
    • Pagetoid spread (MIS) vs melanocytes situated at the dermal-epidermal junction (MH)
    • Irregular MH (MIS) vs regular MH (MH)
    • Deep adnexal involvement (MIS) vs superficial adnexal involvement (MH)
    • Confluence of melanocytes (MIS) vs absence of confluence (MH)
    • Presence of junctional nests (MIS) vs absence (MH)
    • Uniform (MIS) vs nonuniform pigmentation (MH)
    • Flat rete ridges (MIS) vs preserved rete ridges (MH)
    • Pleomorphic melanocytic nuclei (MIS) vs uniform nuclei (MH)
    • Prominent melanocytic dendrites (MIS) vs inconspicuous dendrites (MH)
    • Markedly large and atypical nuclei (MIS) vs large but mildly atypical nuclei (MH)
    • Collapse of cytoplasm around melanocytic nuclei (MIS) vs absence of this feature (MH)
    • Abundant melanophages (MIS) vs few or no melanophages (MH)
  • Subsequent criteria suggested in the literature were:
    • Large, elliptical and irregular nuclei via nuclear morphometry
    • 10% to 20% proliferating melanocytic cells by staining with PCNA or Ki-67/MIB-1
    • Presence of HMB-45 positive melanocytes.
  • Weyers et al evaluated the sensitivity and specificity of all the above criteria, establishing that the most valuable criteria for differentiation were:
    • Presence of nests
    • Irregular MH
    • Deep adnexal extension of melanocytes
    • Pleomorphism of melanocytes
    • Pleomorphism of melanocytic nuclei
  • IHC criteria have been proposed using Mart-1/Melan-A, MiTF and Sox-10 stains to evaluate LM, benign lesions on sun-damaged skin, and background sun damage.
  • MiTF or Sox-10 (nuclear stains) are preferred as to avoid overestimation of melanocyte density with Mart-1/Melan-A (cytoplasmic stain)
  • Photodamaged skin show many criteria originally used for MIS:
    • Increased and irregular melanocyte density
    • Melanocyte confluence
    • Stacking
    • Thèque formation
    • Adnexal extension
    • Suprabasilar scatter
  • Most of these studies were cross-sectional analyses, comparing a variety of patients to each other, which made it impossible to control for factors such as geographic location, anatomic site, age, Fitzpatrick skin type, and history of sun exposure, all of which can influence baseline melanocytic density.
  • The current study found a statistically significant difference in the following histopathologic findings:
    • melanocyte density (per 1mm instead of 0.5 mm in previous studies)
    • irregular melanocyte distribution
    • clustering of melanocytes
    • follicular infundibulum involvement
    • Presence of nests
  • This study was able to control for confounding factors, such as different baseline melanocytic densities, by comparing atypical/malignant biopsies with a sun-damaged control from the same patient.
  • The photodamaged skin samples were taken at least 2 cm from the primary lesion in order to avoid any potential field effect.
  • Although time consuming, assessment of melanocyte density may be an objective and reliable method for diagnosing these complex lesions.
  • Digital imaging may eliminate the need for manual counting in the near future.

Memorable Tweets:

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Thank you so much for attending and for reading this summary. Hope you enjoyed the energy of this journal club,

We are always here for you and your dermatopathology learning,

DermpathJC

#dermpathJC June 2019 summary

#dermpathJC June 2019:

Thursday, June 27th, 9pm EST

Article discussed: Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry

Authors: Huan-You WangMD, PhDYouli ZuMD, PhD

Open access at: https://doi.org/10.5858/arpa.2016-0521-RA

Summary prepared by: Abdullah Alswied, MBBS, MRes, PhD (@AlswiedPath)

 

Journal Club summary:

Study Background: Immunohistochemical profiles of different types of mature B-cell lymphomas, including plasma cell neoplasms exhibit distinct profiles, which enable them to be correctly diagnosed. However, except for rare examples of lymphoma, immunohistochemical profiles of mature B-cell lymphomas overlap and lack specificity.

Objectives:

Three main objectives of the paper:

1- systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10.

2- review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas.

3- review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells

Discussion:

First objective:

Systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10 (Summarized in the table below).

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A- CD5+/CD10- B-cell lymphomas:

– Two classic examples, small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL).

– Lymphoplasmacytic lymphoma (LPL) CD5 expression is anecdotal by IHC.

– Marginal zone B-cell lymphoma (MZBCL) CD5 expression is variable based on its morphologic type.

– Diffuse large B-cell lymphomas (DLBCLs) expression of CD5 is seen in 10% of the cases. It is interesting to note that these lymphomas (CD5+) have higher rates of BCL2 expression.

B- CD10+/CD5- B-cell lymphomas:

– Follicular lymphoma (FL) and Burkitt lymphoma (BL) are the 2-prototypical B-cell lymphomas expressing CD10. The authors recommend a minimal IHC panel for FL should include BCL2, CD3, CD10, and CD20; however, ideally, BCL6, CD5, and CD21 should be included as well.

– Hairy cell leukemia (HCL) and MCL can occasionally be positive for CD10. The authors noted that CD10+ expression in MCL is related to a distinct GC signature rather than an immunophenotypical aberrancy.

– DLBCL: Although approximately 90% of DLBCLs NOS are negative for CD5 and10% to 40% of de novo DLBCLs NOS are positive for CD10.

C- CD5-/CD10- B-cell lymphomas:

– The prototypic CD5-/CD10- mature B-cell lymphomas of small cell size are MZBCL, LPL, and HCL. Most DLBCLs NOS are also negative for both CD5 and CD10.

– In this section, the authors mainly focused on MALT lymphoma and recommended the addition of CD43, lamda and kappa light chains to the panel of IHC.

– Lymphoplasmacytic lymphoma is diagnosed by exclusion, and at times, MZBCL and LPL cannot be distinguished based on morphologic and immunophenotypic features alone.

– The monotypic PCs derived from B-cell lymphoma have a similar immunophenotype to B cells and differ from those of PC myeloma.

– Hairy cell leukemia is positive for all common B-cell antigens with characteristic expression of annexin A1.

– After excluding CD5+ and/or CD10+ DLBCL NOS, approximately 50% to 70% of de novo DLBCLs NOS are negative for both CD5 and CD10.

Second Objective:

Review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas.

– CD38 and CD138 can not differentiate neoplastic PCs derived from PCM from PCs derived from B-cell lymphomas.

– By flow cytometry, CD19 provided the best criterion for distinguishing between these 2 types of neoplastic PCs as neoplastic PCs from B-cell lymphomas are positive for CD19 and are almost always negative in neoplastic PCs from PCM.

– The combination of BCL1, CD19, CD45, CD56, and CD117 is sufficient to distinguish PCs derived from PCMs and/or plasmacytomas from B-cell lymphomas, even in cases in which there is exuberant plasmacytic differentiation

Third objective:

Review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells.

– Lymphomas discussed in this sections include, plasmablastic PCM; plasmablastic lymphoma (PBL); primary effusion lymphoma (PEL); large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease, and ALK+ large B-cell lymphoma

– CD38, CD138, and MUM1 are positive in all cases of plasmablastic PCM, PBL, and PEL.

– Plasmablastic PCM and PBL cannot be separated from each other based on an IHC panel that includes CD45, CD79a, CD56, and PAX5 and the authors recommend the utilizations of CD19.

– The authors provided no recommended panel for PEL other than utilizing the clinical history and HHV8 immunostain.

– ALK+ large B-cell lymphoma is typically negative for most of the common B-cell antigens but positive for PC markers such as CD138, VS38, EMA, and MUM1.

Conclusion:

1- the presence or absence of CD5 and CD10 expression should be included in the initial immunohistochemistry screening panel for mature B-cell lymphomas, appropriate and judicial use of other B-cell antigens is necessary to ensure correct diagnoses.

2- Plasma cells from plasma cell neoplasias and B-cell lymphomas exhibit overlapping but relatively distinct immunophenotypes; thus, a panel of immunohistochemical markers (CD19, CD45, CD56, and CD117) can be employed for their proper identification.

3- CD138 staining results are almost always positive in a group of aggressive B-cell lymphomas with plasmablastic features, including plasmablastic plasma cell myeloma, plasmablastic lymphoma, andALK-1fllarge B-cell lymphoma.

Some Highlights from the Evening:

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Thank you so much for attending and for reading this summary. We are so excited to plan yet another journal club for next month. Stay tuned.

Kind regards!

DermpathJC

#dermpathJC April 2019 summary

#dermpathJC April 2019: 

Thursday, April 25th, 9pm EST 

 

Article discussed: Erythema elevatum diutinum a rare and poorly understood

cutaneous vasculitis: A single institution experience

 

Authors: Luis A. Sardiña, George Jour, Melissa P. Piliang, Wilma F. Bergfeld

 

Summary prepared by: Juanita Duran, MD; Pathology resident, PGY-3 (@JDuranMD)

 

Journal Club summary:

  • EED is a rare and chronic vasculitis of unknown etiology with variable clinical presentation.
  • The initiation of the disease is believed to occur via activation of cytokines, especially interleukin 8.
  • Its pathogenesis remains unknown, but a leading theory postulates an immune complex-mediated vasculitis (type III hypersensitivity) as the underlying phenomenom (idiopathic or related to immune diseases).
  • Reported associated causes: infections (viral and bacterial), rheumatologic diseases, and hematologic neoplasms.
  • Typically presents as persistent red, raised nodules, and plaques distributed symmetrically on acral surfaces.
  • Mostly involves extensor surfaces of the extremities as a spectrum of lesions.
  • Classic histologic features (although non-specific) are those of leukocytoclastic vasculitis involving the papillary and mid-dermal vessels.
  • Aging and more chronic lesions demonstrate onion skin-like fibrosis surrounding the vessels.
  • Differential diagnoses: leukocytoclastic vasculitis, granuloma faciale, and Sweet syndrome.

 

Methods:

  • Retrospective analysis of five cases of EED from a single institution retrieved over a period of 27 years (1989-2016).
  • Criteria applied for inclusion/diagnosis:
  • Lack of papillary dermal edema and microabscesses with negative direct immunofluorescence (DIF) for Immunoglobulin A deposits arguing against dermatitis herpetiformis.
  • Chronic presentation, and lack of fever arguing against an acute Sweet’s neutrophilic dermatosis.
  • Lack of small vessel deposits as well as a negative serological workup ruling out etiologies, such as mixed cryoglobulinemia and paraproteinemia.
  • Negative direct immunofluorescence except for positive granular vascular deposits of Immunoglobulin M and/or C3.

Salient histopathologic findings are depicted in the image below:

img_6247.png

Discussion:

  • EED is an uncommon but treatable skin condition
  • Various clinical and histologic mimickers exist, histologic ddx includes: bacillary angiomatosis, dermatofibroma, Sweet syndrome, pyoderma gangrenosum, granuloma annulare, granuloma faciale and Kaposi sarcoma.
  • Often associated with HIV, Hepatitis B, E.coli and Streptococcal antigens
  • In this series, women are more often affected than men.
  • One patient was asymptomatic, thus the importance of considering this diagnosis in asymptomatic patients.
  • Up to 40% of patients present with joint pain and arthritis.
  • Can show overlapping characteristics with granulomatous dermatoses and mixed connective tissue disease.
  • Associated to neoplasms (benign and malignant solid tumors)?
  • Clinicopathologic correlation is vital to render a diagnosis due to its heterogeneous presentation.

Highlights from the #dermpathJC session:

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Thank you so much for attending and for reading this summary. We are so excited to plan yet another journal club for you next month. Stay tuned.

Kind regards!

DermpathJC

#dermpathJC March 2019 summary

#dermpathJC March 2019:

 

Thursday, March 28, 9pm EST

Article discussed: Cutaneous Metastases: A Review and Diagnostic Approach to Tumors of Unknown Origin

Authors: Gabriel HabermehlMDJennifer KoMD, PhD

Open access at: https://doi.org/10.5858/arpa.2018-0051-RA

Summary prepared by Silvija Gottesman, MD (@SGottesmanMD)

Journal Club summary:

Cutaneous mets, can present as single or multiple painless lesions (papules, nodules, ulcer) that are discovered at the same time with the primary tumor, before a diagnosis of internal malignancy or many months/years after.

Some studies say breast mets are most common to the skin, some say lung is most common, followed by head and neck and colorectal cancers. In the collective experience of the participants of #dermpathJC, it’s been breast carcinoma metastases.
Here’s an excellent workup algorithm for epithelioid cutaneous mets to the skin.
D2yfHjHUcAAL_gI.jpg
General considerations:
– p63 positive in SCC and in primary cutaneous adnexal carcinomas. CK15 & D2-40 positive in primary cutaneous adenocarcinomas over metastatic adenocarcinomas.
– As such, primary adnexal tumors will generally stain positively for CK7, CK15, D2-40, and p63 and negatively for CK20 and SOX10
– CK7+/CK20- in primary cutaneous adnexal carcinomas, variable CK7/CK20 in metastatic carcinomas.
– SOX10 positive in melanoma, neural and myoepithelial tumors.
LUNG:
– Can be proven with staining for TTF-1, CK7 and Napsin A (non-specific, will stain other tumors, such as large cell neuroendocrine and thyroid tumors).
– Pitfall: some lung adenocarcinomas may stain with Ber-Ep4.
– Small cell carcinoma will stain positive for TTF-1 and CAM5.2, and will be negative for CK7 and CK20.
– Mesothelioma will be positive for LMWK, calretinin, Wilms tumor 1, D2-40 and negative for CEA, TTF-1, and CD31.
GASTROINTESTINAL and HEPATOCELLULAR:
– Most useful initial panel consists of CK7 (non-reactive), and positive CK20 and CDX2. Gastric tumors can be commonly positive for both CK7 and CK20.
– Article seems to suggest CDX2 specific for colorectal primary. Some of the #dermpathJC participants have found this to be positive on many GI adenocarcinomas (upper and lower tract).
– Hepatocellular carcinomas are CK7 and CK20 negative, thus additional markers, such as: HepPar-1 and arginase-1 are helpful.
– In contrast, cholangiocarcinomas are CK7 positive and sometimes CK20 positive, but diffusely CDX2 negative.
GENITOURINARY:
– Renal cell carcinomas: typically nonreactive for CK7, CK20 and positive for pancytokeratin AE1/AE3, EMA, CD31, RCC and CD10. RCC mets are also positive for PAX8, however this is also positive in thyroid, Mullerian, and thymic tumors.
– Pitfalls: CD10 and EMA will stain cutaneous clear cell hidradenomas and sebaceous carcinomas.
– Chromophobe RCC will stain for PAX8, CD117, but will be negative for CD10.
– Urothelial mets: positive for HMWCK, CK7, p63, and S-100P with variable positivity for CK20 & GATA3.
– Prostate adenocarcinoma: negative for CK7, CK20, positive for PSA, NKX3.1, CD57, and Ber-Ep4.
BREAST:
– Both breast carcinomas and adenxal neoplasms are typically CK7 positive and CK20 negative.
– Breast carcinomas typically positive for: CK19, MUC1), ER, PR and mammaglobin, but nonreactive for CK5/6 and TTF-1.
– In contrast, pagetoid SCC will be p63 and CK5/6 positive, but mammary and extramammary Paget’s will be p63 negative and CK7+.
– The most useful IHC to differentiate between metastatic breast and primary cutaneous tumors – majority of the participants recommend p63 in conjunction with history and imaging. Sweat gland carcinomas strongly express p63, CK14, CK5, and CK17, however, the latter three immunohistochemical stains are not readily available in all labs.
– GATA3 stains breast carcinomas strongly, but has also been shown to be positive in trichofollicular and sebaceous neoplasms, as well as urothelial carcinoma, parathyroid gland neoplasms, salivary gland neoplasms, and pheochromocytomas.
GYNECOLOGIC:
– Ovarian and endometrial: CK7+ and PAX8+, Endocervix adenocarcinomas: CK7+ and EMA+/-. All three are CK20 negative and show variable ER and PR expression. Endometrioid morphology ddx includes pilomatrical carcinomas, in this instance p63 will be helpful to differentiate primary cutaneous adnexal neoplasm from a metastasis.
MELANOMA:
– Metastases are S100 and SOX10 positive. Melan-A and HMB-45 can be variable.
LYMPHOMA and LEUKEMIA:
– Authors suggest that CD3, CD20, CD30 and muramidase panel is helpful for initial evaluation of atypical lymphoid infiltrates, however majority of the #dermpathJC participants agree that this is a very limited initial panel and should also include: PAX5 always for B-cells and at least 2 markers for each cel lineage.
SARCOMA:
– True metastatic sarcomas to the skin are extremely rare.
– An entity worth noting: epithelioid sarcoma, which has high metastic potential and high mortality. These show positivity for CD34 in up to 50% of cases, as well as CK AE1/3 and EMA. SMARCB1/INI1 22q11 deletion via loss of nuclear INI1 staining.
That’s all folks for now, until next #dermpathJC, stay happy and curious,
Sincerely,
Silvija Gottesman, MD

#dermpathJC February 2019 summary

#dermpathJC February 2019:

Thursday, February 21, 9pm EST

Article discussed: Solid carcinoma is a variant of microcystic adnexal carcinoma: A 14‐case series

Authors: Yosmar Carolina, Perez-Gonzalez, Ramon Bosch-Princep, Maria-Teresa-Fernandez-Figueras, Arno Rutten.

Temporary open access at: https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13351

Summary prepared by Abha Soni, DO, MPH (@AsoniDO)

 

Journal Club summary:

This month’s journal club discussed a rare skin neoplasm that closely resembles the solid areas of microcystic adnexal carcinoma (MAC). The article was a good review of the histologic, and immunohistochemical features of this entity.

In case you missed our discussion this week, the summary is provided below:

Only 16 cases of sold carcinoma have been previously published. This paper presents 14 additional cases of sold carcinoma and reviews their morphologic and immunohistochemical features.

Histology:

  • Groups of neoplastic epithelial cells with small monomorphous nuclei.
  • Cells form small solid aggregates that vary in size and shape and fill the dermis and extend through adipose tissue.
  • Nuclear atypia and mitotic figures are rare.

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  • Perineural invasion and infiltrative borders are identified.

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  • Small cornifying cysts/follicular derived cysts can be found in the upper part of the neoplasm.

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  • Some nests show clear cell features without a prominent basal cell layer.
  • These cells showed abundant cytoplasm, single nucleolus, and their nuclei tended to be located near the apices of the cells

Screen Shot 2019-03-13 at 12.47.02 PM

Immunohistochemistry:

  • Neoplastic cells exhibit high-molecular weight keratin (cytokeratin 5/6), broad specterum keratin (AE1/AE3), and p63, with focal CEA immunoreactivity.
  • Negativity for ER, PR, BerEP4, EMA, Cytokeratin 7, Cytokeratin 20, Cytokeratin 18, SMA, S-100, CD15, and GCDFP-15.
  • p53 is associated with uncontrolled proliferation and interpreted as an indicator of aggressive behavior and was only expressed in less than 5% of cells in the tested cases.
  • p63 shows a homogenous expression than in classic MAC.
  • CK19 is positive in some small ductal structures within the neoplasm
  • PHLDA-1 was negative in the cases studied (unlike previous papers). It appeared to stain part of the epithelium of cystic structures.

Screen Shot 2019-03-13 at 12.47.19 PM

Discussion:

  • Clinicians must determine whether this is a unique clinicopathologic entity or if it belongs to the spectrum of MAC.
  • Differential diagnosis includes:
    • Clear-cell dermal duct tumor
      • Differentiating features: Absence of cystic structures on the superficial aspect of the neoplasm in dermal duct tumor, and absence of infiltrative pattern without perineural invasion.
    • Sclerosing basal cell carcinoma
      • Differentiating features: BerEP4 would be positive in both sclerosing and clear cell BCC and negative in solid carcinoma/solid variant of MAC.
    • Desmoplastic trichoepithelioma
      • Tumor cells are basaloid and show presence of rims of collagen bundles around the neoplastic cell cords as well as absence of perineural involvement. Additionally, are confined to the upper/mid dermis.
    • Solid variant of MAC vs classic MAC:
      • Classic MAC clinically presents in locations such as lips and face and rarely the scalp. Whereas, the current series, scalp location seems to be more associated with the solid variant of MAC.
    • Solid carcinoma should be referred to as the solid variant of MAC, histopathologic features of this entity belong to the MAC morphologic spectrum.


See you all next month
! 😉

#dermpathJC January 2019 summary

#dermpathjc January 2019:

Thursday, January 24, 9pm EST

Article discussed: Pigmented Lesions of the Nail Unit

Authors: Nevares-Pomales O, Sarriera-Lazaro C, Barrera-Llaurador J, Santiago-Vazquez M, Lugo-Fagundo N, Sanchez JE, Sanchez JL.

Temporary open access at: https://journals.lww.com/amjdermatopathology/Abstract/2018/11000/Pigmented_Lesions_of_the_Nail_Unit.1.aspx

Summary prepared by Patrick Rush, DO (@DrPatrickRush)

 

Journal Club summary:

This month’s journal club article discussed a topic that gives many of us much consternation, pigmented lesions of the nail unit. The article was a good overall review in many regards; there was discussion (with images) of the clinical features of melanocytic lesions and the concerning signs, as well as a review of the epidemiology, histology, and molecular findings. The learning objectives for the article were very well laid out, and there are accompanying CME questions for obtaining AMA PRA Category 1 credits.

It was a lively discussion, and those active in the discussion overall agreed with the author’s summary and findings.

There were a few take home points from the paper and subsequent discussion, which touched on all aspects:

Embryology:

  • Proximal nail matrix = predominantly dormant melanocytes
  • Distal nail matrix = active and dormant melanocytes (more likely for a melanocytic lesion to arise within this zone)

Epidemiology:

  • Melanocytic macule more common in adults
  • Nevi more common in children

Clinical:

  • Longitudinal melanonychia not always due to a melanocytic lesion (Fungus, drugs, trauma, infection, etc can be causative)
  • Amelanotic subungual melanoma has been reported at rates between 15-50% (while they only comprise 2-8% of melanomas at other sites)

Sampling:

  • Many seem to groan with nail clippings to evaluate for a melanocytic lesion
  • If clippings are sent, if negative they will usually be emblazoned with a caveat in an comment

Histology:

  • Most peoples malignant lesions have been composed of melanoma in situ with invasive melanoma making up the minority.

Immunohistochemistry:

  • SOX10 not as useful in the nail unit as in other parts of the body
  • Mart-1 / Melan A are preferred, and felt to work better
  • Some also order a Fontana Mason in addition

Molecular:

  • Subungual melanoma more commonly harbor KIT mutations
  • Predictions through immunohistochemistry has thus failed to be predictive of molecular aberrations
  • Gold standard for interrogation of KIT mutations remains molecular analysis

Some Highlights from the Evening:

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Jan2

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Top: nail plate chromomycosis

Bottom: nail plate onychomycosis

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The conversations were great again, with a nice mix of Dermatologists and Pathologists from all over the world. Hope to see you again next time!

 

#dermpathJC December 2018 summary

Thursday, December 27, 9pm EST

Article discussed: Selected Pseudoneoplastic Lesions of the Skin

Author: Mark R. Wick and James W. Patterson

Open access at: http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165-134.3.369

Summary prepared by Jisun Cha, MD (@sunpungi)

 

Journal Club Summary:

Hair follicle “bulges” (der Wulst) are commonly seen in dermpath sections. How they differentiate from BCC – usually vertically oriented, surrounded by normal dermis, prominent basement membrane, no mitoses, no atypia and lack of myxoid stroma. Normal structure of hair follicles in the central facial skin.

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PEH (Pseudoepitheliomatous hyperplasia) can be associated with many different types of lesions. Here is a nice summary table from @SGottesmanMD.

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Most dermpathJC participants agree that verrucous carcinoma can be quite impossible to distinguish from pseudoepitheliomatous hyperplasia in certain scenarios. This is where additional clinical information may be helpful.

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Pseuodsarcomatous fibroepithelial polyp – fatty core which shows pleomorphic lipoblast-like cells which have similarity to pleomorphic lipomas and some deep soft tissue sarcomas (liposracoma). These changes are thought to be of a degenerative nature. They are very rare as most dermpathJC participants have never seen such changes in fibroepithelial polyps. @JMGardnerMD is wondering if some of these are in the pleomorphic fibroma/lipoma spectrum, and would be cool to do RB1 on a specimen like this. Additional reading about loss of retinblastoma in pleomorphic fibroma: https://www.ncbi.nlm.nih.gov/m/pubmed/28543636/

3Acroangiodermatitis of Mali aka dermatitis hemostatica aka Bluefarb-Stewart syndrome aka pseudo-Kaposi sarcoma. Here’s another useful table from @SGottesmanMD.

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4

Reactive angioendotheliomatosis (term used in several different ways and is still confusing to most participants)

  • Reactive vascular proliferation
  • Reactive histiocytes proliferation filling dilated vessels

5

And last but not least, basaloid, follicular and sebaceous induction over a dermatofibroma. Photos by , and

9

10

11

Hope you have a happy New Year and we will see you January 24th, 2019 at 9pm EST for another exciting dermpath journal club.

 

Kind regards,

Silvija Gottesman, MD

#dermpathJC November 2018 summary:

Thursday, November 29, 9pm EST

Book discussed: WHO Classification of Skin Tumours

Special Guests: Dr Richard A. Scolyer (@ProfRScolyerMIA) and Dr Rajendra Sing (@mydermpath)

Summary prepared by Abha Soni, DO, MPH (@AsoniDO)

 

Journal Club Summary:

Topics Discussed:

 Variants of cutaneous SCC:

    1. Squamous cell carcinoma (NOS)
    2. Keratoacanthoma*
    3. Verrucous SCC*
    4. Acantholytic SCC
    5. Adenosquamous SCC
    6. Spindle cell SCC
    7. Rare variants (Lymphoepithelial-like SCC, Pseudovascular SCC, and SCC with sarcomatoid differentiation)

*These low-grade variants can be locally destructive but have little potential to metastasize

2.jpg

Basal Cell Carcinoma:

  1. Lower Risk: Superficial, nodular, pigmented, infundibulocystic, Fibroepithelioma of Pinkus
    • Fibroedpitheloma of Pinkus, aka Pinkus tumor renamed as fibroepithelial basal cell carcinoma
  2. Higher Risk: Micronodular, infiltrating, morpheaform/sclerosing, basosquamous carcinoma, BCC with sarcomatoid differentiation
    • Micronodular: irregular, infiltrative deep/peripheral edges. Defined as >50 small nodules (<0.15 mm in diameter)
    • Infiltrating: Small irregular/jagged nests, at least 5-8 cells thick at least
      1. In contrast, Dr. Singh explained that morpheaform can be less than 5 cells thick. “In short, morpheaform tends to have smaller basaloid nests. But to stress again many consider them as same of overlapping features.”
      2. Others commented that in the morpheaform subtype they also look for dense fibrous/keloid-like collagen fibers

Basosquamous: Zones contain cells with intermediate features between the two. The basaloid component stains positive for BerEP4 and the squamous areas express MUC1 (EMA)

Melanocytic Tumors:3

  • This new approach to melanoma classification was appreciated by many in the Dermpath JC twitter community as there is a higher emphasis on the chronicity of sun damage and how it impacts certain pathways in melanoma progression.
  • Two main pathways CDKN2A pathway and the MAPK pathway were discussed.

 

Dysplastic Nevi:

Low Grade: Moderate cytologic and architectural atypia

High Grade: Severe cytologic and architectural atypia

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BAPOMA: Combined nevus with a benign nevic component and almost a spitzoid component. Some spitz like areas show multinucleation with an admixed infiltrate.

BAP1 lost especially present in the larger cells. BRAF mutations mostly also seen.

 

New Entities:

  1. Endocrine mucin producing sweat gland carcinoma
    • Low-grade neuroendocrine neoplasm
    • Predilection for eyelid and periorbital skin. However, occurrence in an extrafacial location has also been reported.
    • Precursor of mucinous carcinoma
    • Older individuals (i.e. in the sixth and seventh decades of life)
    • Positive for CK7, CK8, CK18, AE1/AE3, CAM5.2, EMA, GCDFP15, WT1, ER and PR. Intensity for chromogranin and synaptophysin varies. Ki-67 is low.
  2. Squamoid eccrine ductal carcinoma
    • Present as large nodules and plaques in the head and neck area.
    • Positive for cytokeratin and ductal differentiation can be confirmed by MUC1 and CEA.
  3. Secretory carcinoma of the skin
    • Axillary location.
    • Rare sites include the face (including the lips), trunk, and limbs.
  4. Signet ring cell/histiocytoid carcinoma
    • Males>females
    • Predilection for eyelids, but identical neoplasms have been reported in the axilla.
  5. Hematolymphoid tumors
    1. CD30 lymphoproliferative disorders
      • Types A-C morphologic criteria remain the same.
      • Type D: shows epidermotropic infiltrates of CD8+ and CD30+ atypical cells and mimics primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.
      • Type E: characterized by angiocentric and destructive infiltrates, predominantly medium sized atypical CD30+ lymphocytes with extensive dermal necrosis and ulceration.
    2. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder
      • Solitary skin lesion, and no evidence of the patches or plaques.
      • Ulcer/papules show spontaneous regression.
      • Expression of PD-1(follicular T-cell marker), monoclonality of T-cell receptor (60%).
      • Similar phenotype has been observed in patients with multiple lesions. This is still an understudied area and it is important to recognize for therapeutic options and to determine prognosis.

Soft tissue tumors:

  1. New Entities
    • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma
      1. Spindled to epithelioid, rarely metastasizing neoplasm
      2. Mimics myotid tumor or epithelioid sarcoma
      3. SEPINE1-FOSB fusion
      4. Male predominance
      5. Lower extremities > upper extremities or trunk
      6. FOSB consistently positive
    • Cutaneous leiomyosarcoma
      1. Prognosis of these tumors is superb, no metastases
      2. Grading is not of prognostic value
    • Angiosarcoma
    • Majority associated with radiation or preexisting lymphedema are associated with MYC gene amplification and co-amplification of FLT-4.
      1. This may be helpful in cases where MYC amplification is not seen.

 

 Special thanks to Dr. Singh (@mydermpath) for putting the presentation together and to the @DermpathJC twitter community for another successful discussion.

 The detailed slides/summary and accompanying virtual images can be accessed here:

 Pathpresenter.net

Login: pp@gmail.com

Password: welcomepp

Click on: My presentations

Click on DermpathJC

 Here are the corresponding diagnoses to the online virtual images: 

  1. Keratoacanthoma
  2. Verrucous carcinoma
  3. Micronodular basal cell carcinoma
  4. Morpheaform BCC
  5. Infiltrative bcc
  6. Bapoma
  7. Trichoblastic carcinoma
  8. Secretory carcinoma
  9. Endocrine mucin producing sweat gland carcinoma
  10. Signet ring/histicocytoid carcinoma
  11. Squamoid eccrine carcinoma
  12. CEA
  13. Adnexal adenocarcinoma NOS
  14. Leiyomyosarcoma
  15. Pseudomyogenic hemangioendothelioma
  16. Epithelioid histiocytoma
  17. Type E LYP
  18. Erdheim Chester Disease
  19. Conjunctival melanoma
  20. Conjunctival primary acquired melanosis
  21. Conjunctival nevus

 

Thanks to all who participated! See you in December! Save the date 12/27/2018, 9pmEST.

Kind regards,

Silvija Gottesman, MD

#dermpathJC October 2018 summary:

#dermpathjc October 2018:

Thursday, October 25, 9pm EST

Article discussed: Verruciform and Condyloma-like Squamous Proliferations in the Anogenital Region.

Author: May P. Chan from the Archives of Pathology and Laboratory Medicine

Free access at: http://www.archivesofpathology.org/doi/10.5858/arpa.2018-0039-RA

Summary prepared by Dr. Katy Veprauskas (@LinskeyKaty)

 

Journal Club Summary:

Background: Histologic distinction between condyloma acuminatum and various benign and malignant condyloma-like lesions in the anogenital area poses a common diagnostic challenge to pathologists across subspecialties.

Aim of study: To review the overlapping and distinguishing features of condyloma acuminatum and its mimics, and to clarify confusing terminology and diagnostic criteria for problematic entities.

Results: Correct diagnosis of condyloma acuminatum and condyloma-like lesions has important clinical implication and entails familiarization with their clinical presentations and histopathologic features. Contrary to historical belief, giant condyloma acuminatum and verrucous carcinoma should be considered distinct entities based on different pathogenetic pathways. Ancillary tools available for identifying and genotyping human papillomavirus can aid in diagnosis when histopathologic findings are inconclusive. Recognition of relatively rare entities such as bowenoid papulosis, epidermolytic acanthoma, and verruciform xanthoma would avoid overdiagnosis and unnecessary, overaggressive treatment.

Limitations: This was a literature review and did not present original data.

Twitter Journal Club Discussion Summary:

● Issue of vulvar SK (HPV and non-HPV related) was discussed; approaches include:

○ Consideration of age: younger patients generally more likely to be HPV+ and less likely to have SK in general

■ ASDP AUC used 25 yrs old as cutoff; SK very rare under that age

■ study of vulvar SK in women >50 yrs showed low incidence of HPV+, with 3/28 patients HPV+ (14%; vs other studies which showed closer to 70% in younger pts) (Reutter J, J Low Genit Tract Dis. 2014, https://www.ncbi.nlm.nih.gov/pubmed/24556611 )

○ Koilocytes helpful in diagnosing condy vs SK

○ Many participants favor a descriptive diagnosis and offer HPV testing in comment upon clinician request

○ Ki67 helpful for some; staining in upper layers of the epithelium more supportive of condy (Pirog et al AJSP 2000, Bai et al Hum Pathol 2003)

● HPV testing on low grade lesions:

○ Modalities: ISH appears most popular (though some use PCR), sendout labs used included ARUP and Mayo

○ Most do not order HPV testing routinely; will order upon clinician request

○ Important to note that there can be false positives and false negatives; some condy can be caused by high risk or HPV types other than 6/11, so condy that comes back as HPV low risk negative by ISH may be a false negative

○ HPV testing was reviewed in ASDP appropriate use committee (AUC):

https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13142 ; found HPV testing “rarely appropriate” in many scenarios, exception being pediatric cases with path suggestive of condy (HPV testing “usually appropriate” in these cases)

● LAST terminology was discussed: many participants incorporate LSIL and HSIL into diagnosis of HPV related lesions of the anogenital region

○ Some only use “condyloma” for papillomatous low grade squamous lesions in the vulva and reserve LSIL for lesions that appear flat, others use both terms (“condyloma (LSIL)”)

○ It was noted that the ISSVD (International Society for the Study of Vulvovaginal Disorders) published terminology in 2015 highlighting specific issues related to vulvar SIL in the LAST criteria; they noted that LSIL should be used in regards to “flat condyloma or HPV effect” and also emphasized that LAST does not refer to differentiated VIN, which is considered a separate, non-HPV related form of high grade VIN (https://www.ncbi.nlm.nih.gov/pubmed/26704327 )

● Diagnosis of bowenoid papulosis relies on clinical correlation; suggested approach by some participants would be to diagnose case as HSIL/VIN3 and add comment that it could be c/w bowenoid papulosis in the appropriate clinical setting

● Giant condy vs verrucous CA:

○ traditionally (and still in some texts) taught that both are HPV-related, but while giant condy is usually associated with HPV 6/11, verrucous CA not HPV-related in studies with cases defined by strict histopathologic criteria

○ Giant condy usually associated with other STDs, VC assoc w/ inflammatory conditions such as lichen sclerosus

Thanks to all who participated! See you in November!