#dermpathJC September 2019 summary

#dermpathJC September 2019: 

Thursday, June 26th, 9pm EST

Article discussed: An Immunohistochemical Panel to Differentiate Metastatic Breast Carcinoma to Skin From Primary Sweat Gland Carcinomas With a Review of the Literature

Authors: Marian Rollins-Raval, MD, MPH; Mamatha Chivukula, MD; George C. Tseng, ScD; Drazen Jukic, MD, PhD; David J. Dabbs, MD

Open access at: https://doi.org/10.5858/2009-0445-OAR2

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

 

Background: 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)

Objectives: Recommend a panel of IHC stains to distinguish CMBC from SGC.

Design: 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).

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

Image

  • 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:

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And last but not least:

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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 and have fun at the upcoming #ASDP2019.

 

Kind regards!

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 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.

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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
! 😉