Journal Club Summary:

Cutaneous metastases of breast cancer (CMBCs) is observed in 25% of patients diagnosed with breast carcinoma and can be difficult to distinguish from sweat gland carcinomas (SGCs). Panel of eight IHC stains were used in four group of cases; ductal CMBCs (12 cases), SGCs (12 cases), benign sweat gland neoplasms (2 cases) and breast cancer cases (2 cases).

Discussion:

• The authors first started by performing a literature review on previous studies and have concluded the following:

1. ER, PR, CK7, and CK20 stains are not useful markers to differentiate the two entities.
2. GCDFP-15, carcinoembryonic antigen, EGFR, CK5/6, podoplanin, and p63 are potential candidates and three stains from this list were further investigated in the current study (GCDFP-15, CK5/6, and p63)

• CK14, CK17, AR, mammaglobin, and PAX5 were investigated in this study in addition to the three described above.
• Out of the 8 stains that were investigated, only P63 and CK5 demonstrated sustained potential in distinguishing CMBC from SGC.
• combining mammaglobin, p63 and CK5 with CK14, and CK17 consistently differentiates CMBC from SGC in the cases reviewed in this study.
• Limitations of the study included number of cases reviewed which is understandable given the rarity of these neoplasms. Moreover, combined with the low number of cases, heterogeneity among the groups of tumors examined and subgroups classification was another challenge of the study limiting the examination of certain subgroups (one case of basal-phenotype CMBC).

Conclusion:

• The authors recommended a panel of five IHC composed of mammaglobin, p63, and 3 basal cytokeratins to be able to differentiate between CMBCs and SGCs neoplasms (See the table below).

Image from Archives of Pathology and Laboratory Medicine (open access):

• P63 was expressed in 90.9% of SGCs, whereas it was expressed im 8.3% of CMBCs cases.
• Basal cytokeratins was expressed in 90.9% of SGCs and up to 16.7 in CMBCs (0% CK14 to 16.7% of cases expressing CK5 and CK17.
• Mammaglobin was expressed in 16% of SGCs and in 66.7% of CMBC.

In sum:

Skin primary sweat gland carcinoma generally mammoglobin-, p63+, CK5+, CK14+, CK17+ Cutaneous mets of breast carcinoma generally mammoglobin+, p63-, CK5-, CK14-, CK17- ER, PR, CK7, CK20, CEA, EGFR & GCDFP-15 stains not effective in differentiating between the two.

Some Highlights from the Evening:

And last but not least:

Thank you so much for attending and for reading this summary. We are so excited to plan yet another journal club for next month. Stay tuned and have fun at the upcoming #ASDP2019.

Kind regards!

DermpathJC

#dermpathJC August 2019:

Thursday, August 22nd, 9 pm EST

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

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

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

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

Journal Club Summary:

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

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

Memorable Tweets:

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

On summer vacation 🙂

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

Temporary free access courtesy of Journal of Cutaneous Pathology: 10.1111/cup.13378

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:

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:

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

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.

• Perineural invasion and infiltrative borders are identified.

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

• 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

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.

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! 😉

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:

Top: nail plate chromomycosis

Bottom: nail plate onychomycosis

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!

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.

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

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.

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/

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

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

• Reactive vascular proliferation
• Reactive histiocytes proliferation filling dilated vessels

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

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

Journal Club Summary:

Topics Discussed:

 Variants of cutaneous SCC:

1. 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

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:

• 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

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