#dermpathJC June 2018 summary:

#dermpathJC June 2018:

Thursday, June 28th, 9pm EST

Article discussed: The pathological spectrum and clinical correlation of pigmented purpuric dermatosis – A retrospective review of 107 cases

Authors: Yen-Kai Huang, Cheng-Kuan Lin, Yu-Hung Wu

Temporary open access available at https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.13118

Summary author: Andrea Primiani Moy, MD (@aprimi)

Journal Club Summary:

This month’s journal club article reviewed the clinical and pathologic features of the variants of pigmented purpuric dermatosis (PPD). PPD is a group of skin diseases characterized by the petechiae/purpura with increased pigmentation on the skin of the lower extremities. The clinical variants can be summarized as follows (with Schamberg’s being the most common):

Screen Shot 2018-07-07 at 10.06.01 AM

Interestingly, PPD has been associated with diabetes, autoimmune disease, and hypersensitivity to medications. Granulomatous PPD has been associated with hyperlipidemia.

The authors in this article reviewed 107 cases diagnosed pathologically with PPD over the course of nine years at a tertiary referral centers. Clinical photos and pathology slides were reviewed to ensure an accurate clinicopathologic diagnosis. The authors reviewed the pathological patterns present. Clinical data was also reviewed, and follow-up at one month post biopsy was collected.

Clinical features of the cases studied were discussed. Pigmented purpuric dermatoses – about equivalent male to female ratio, lower extremities involved most frequently (96.3%) and lesions bilateral in 79.4% (Huang et al’s findings).

The histologic patterns seen in biopsy specimens are shown in Figure 1. Spongiotic, Interface, Lichenoid, Perivascular and Granulomatous. Note that the lichenoid and perivascular patterns were most common.

fig 1

Also, epidermal changes were common, as demonstrated in this figure:

fig 2

It was noted that lymphocyte exocytosis may mimic mycosis fungoides (MF) in these biopsies. While no patients in this study were diagnosed with MF at one year following the biopsy, an interesting point and discussion was raised – that they either may declare themselves at a later time or a good handful of patient with atypical lymphocytic proliferation never even meet criteria for Stage IA Mycosis Fungoides.

Based on their statistical analysis, the authors reported that the perivascular pattern was typically seen with Schamberg disease, the lichenoid pattern was seen in lichen aureus or Schamberg disease, the spongiotic pattern was seen with an eczematoid-like purpura, and the interface and granulomatous patterns could appear as any of the clinical variants. Thus, making a clinical diganosis based on histologic features is difficult. However, in contrast, some clinical variants had a predictable pathologic findings – lichen aureus usually shows a lichenoid pattern; Schamberg disease usually showed a perivascular pattern, and a spongiotic pattern was often seen in an eczematoid-like purpura.

The authors also correlated pathologic features with comorbid conditions. The interface pattern was associated with a higher rate of autoimmune disease and gout. All patterns were associated with similar rates of hypertension, hyperlipidemia, and diabetes.

The clinicopathologic features were nicely summarized in this table:

Screen Shot 2018-07-07 at 10.17.49 AM

Given the variation in pathologic features seen in PPD, this article helps to increase awareness so the diagnosis may not be missed.

Many thanks Dr Andrea Moy for the post journal club summary. See you all at the next #dermpathJC on August 30th at 9pm EST for a fun and lively discussion of a cutting edge #dermpath article in realtime via twitter! In July, #dermpathJC will be on a summer break.

Kind regards,

Silvija Gottesman, MD

#dermpathJC May 2018 summary:

#dermpathJC May 2018:

Thursday, May 24th, 9pm EST

Article discussed: Cutaneous and Superficial Soft Tissue CD34+ Spindle Cell Proliferation

Authors: Hongyu Yang, MD, PhD and Limin Yu, MD, MS

Archives of Pathology & Laboratory Medicine: August 2017, Vol. 141, No. 8, pp. 1092-1100

Open access available at: https://doi.org/10.5858/arpa.2016-0598-RA

Summary author: Patrick Rush, DO (@DrPatrickRush)

 

Journal Club Summary:

CD34 is an often-utilized stain in dermpath. Unfortunately, a wide array of spindle cell tumors in the superficial soft tissues (dermis and subcutis) are CD34 positive. CD34 expression can be a prominent feature of fibrohistiocytic neoplasms but also of neural neoplasms, lipogenic neoplasms, and neoplasms of uncertain histiogenic lineage.  In the discussed Archives article Drs. Yang and Yu gave us a great review of these entities with a nuanced discussion of the unique challenges that this heterogeneous group of superficial CD34+ lesions can present. The discussion was focused around four case-based examples.

Screen Shot 2018-06-03 at 10.27.30 AM

 

 

Brief summary of the Case-Based Entities Discussed:

 

Cellular Digital Fibroma:

Clinical: Acral sites, such as fingers and toes, small <0.5cm papule

Demographics: 33-83yo, no sex predilection

Behavior: Indolent (no recurrence after complete excision)

Histology: Proliferation of uniform slender fibroblasts forming fascicles in parallel or haphazard arrangement in the upper dermis with dense dermal collagen.

Immunoprofile:

Positive: CD34

Negative: S100, EMA, Factor XIIIa

Differential Diagnosis:

  • Early DFSP: Also CD34+. Distinguished clinically, DFSP rarely occurs in the digits of adults. DFSP occurs as a plaque with slow growth, not as a small <0.5cm papule
  • Superficial Acral Fibromyxoma (Digital Fibromyxoma): Also CD34+, but larger (0.5-5cm) with a distinct myxoid stroma.

Background: Described by McNiff and colleagues in 2005 where this entity was noted to be a unique subset of digital fibromas in their practice.

Screen Shot 2018-06-03 at 11.39.07 AM

 

Superficial CD34+ Fibroblastic Tumor:

Clinical: Slow growing painless mass (1.5-10cm, mean 4.1cm) occurring in the extremities, most commonly in the lower extremity and buttock.

Demographics: Occurs exclusively in adults, 20-76yo, no sex predilection

Behavior: Indolent (of 13 patients 12 had no recurrence, 1 patient developed a lymph node met after 7-years)

Histology: Proliferation of moderately cellular spindled to epitheloid cells with abundant granular to glassy cytoplasm and bizarre hyperchromic nuclei with “alarming” nuclear pleomorphism and a paradoxically low mitotic count and proliferative index in a proliferation (<1/50 HPF). Often there is a prominent inflammatory infiltrate of lymphocytes and mast cells.

Immunoprofile:

Positive: CD34, keratin (focal weak), Intact INI-1

Negative: S100, Desmin, SMA, ERG, FLI-1, TP53

Differential Diagnosis:

  • AFX & Pleomorphic Dermal Sarcoma: Differentiated by the clinical and histology. Clinically these tumors both more typically occur on more chronically sun damaged skin, such as the head and neck (as opposed to the leg and buttock). These tumors will have a high mitotic count, and expression of TP53.
  • Myxoinflammatory Fibroblastic Sarcoma (Inflammatory Myxohyaline Tumor of the Distal Extremities) (MIFS): This tumor also has bizarre nuclear cytology combined with a low mitotic rate, and prominent inflammatory infiltrate with scattered keratin positivity. But MIFS will be CD34- and will have rearrangements of TGFBR3 and MGEA5
  • Pleomorphic Hyalinizing Angiectatic Tumor (PHAT): Again Strikingly pleomorphic but with a low mitotic count. Distinguished by the presence of characteristic ectatic hyalinized blood vessels and abundant hemosiderin deposition.
  • Epithelioid Sarcoma: May comes into the differential sue to its shared phenotype of Keratin positivity with CD34 positivity. Distinguished by their granulomatous appearance from low power, necrosis, and their loss of INI-1 expression.

Background: Described in Carter and colleagues in 2013 when they determined that there was a distinct morphology in a subset of their low-grade fibroblastic tumors.

Screen Shot 2018-06-03 at 12.37.35 PM

 

Spindle cell Lipoma:

Clinical:  Solitary subcutaneous mass on the posterior neck, shoulder, and back, typically 3-5cm.

Demographics: Adult males 40s-60s

Behavior: Indolent

Histology: The typical histologic presentation is of mature adipocytes, short, cytologically bland spindle cells, and “ropey” collagen bundles, often with prominent mast cells in the background. This typical histology is not the scenario where there will be much diagnostic difficulty, is in the “fat-free” spindle cell lipoma where the paucity of the mature adipocyte component may cause some befuddlement, in this scenario it can be important to know that the bland spindle cells are CD34+.

Immunoprofile:

Positive: CD34 (spindle cell component), S100 (Adipocyte component)

Negative: S100 (spindle cell component), STAT6

Differential Diagnosis:

  • Neurofibroma: While also a infiltrative tumor of bland spindled cells, these are CD34- and S100+ in the spindle cells.
  • Solitary Fibrous Tumor: This histologic differential can be difficult if there is fat infiltration. Though they typically have a biphasic appearance and staghorn vasculature. In addition, when these tumors uncommonly occur in the skin, the head and neck is where they commonly occur. They can be differentiated by STAT6 positivity and clinical correlation.

Background: The “fat-free” or “low-fat” variant of spindle cell lipoma is a well-known diagnostic stumbling block.

Screen Shot 2018-06-03 at 1.02.04 PM

 

Plaque-like CD34+ Dermal Fibroma (Medallion-Like Dermal Dendrocyte Hamartoma):

Clinical:  Medallion-like round-to-triangular well-circumscribed brown atrophic plaques (6-10cm in diameter) on the central chest and neck since birth (most but not all are congenital).

Demographics:

Behavior:

Histology: Epidermal atrophy with a distinct band-like proliferation of fusiform cells in the upper dermis, concentrically arranged around small vessels and nerves.

Immunoprofile:

Positive: CD34, Factor XIIIa (positive in original series, negative in other subsequently described cases)

Negative: S100, Cytokeratin AE1/AE3, Actin, Desmin, NSE, Neurofilament

Differential Diagnosis:

  • Congenital/atrophic DFSP: Cytogenetic and molecular analysis can help in this distinction. To date, no cytogenetic profile has been ascribed to this entity, unlike DFSP.

Background: Rodriguez-Juardo et al first described this entity in 2004, where they proposed that these lesions represented a hamartomatous process. Since this time the clinical spectrum has been expanded to include de novo occurring lesions in adults. There is some disagreement amongst authors concerning the consideration of de novo tumors in adults and the congenital lesions with a specific clinical scenario as the same or distinct entities.

In short – The May 2018 #dermpathJC discussed the histologic and clinical differentials of CD34+ tumors that arise within dermis and superficial subcutis, and live discussion with the authors. Here are some selected #pearls from the evening discussion.

Screen Shot 2018-06-03 at 1.54.51 PM

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There were 1.177 Million impressions of the meeting over the following weekend with 333 tweets and 64 Participants. The discussion was lively, as always, with attendees checking in from around the world from Brooklyn, NY, to Chile and many places in between. We were very happy to have the authors in attendance, Dr. Limin Yu (@Wikilip) and Dr. Hongyu Yang (@HENRYY_MD). Having the authors present to discuss their work with interested readers in real time is just one aspect of the #dermpathJC twitter format that stands it apart from traditional journal club formats; allowing for meaningful insight into the authors struggles and thoughts that you might have otherwise not known.

Many thanks Dr Patrick Rush for the summary. See you all at the next #dermpathJC on June 28th at 9pm EST for a fun and lively discussion of a #dermpath article in realtime via twitter!

 

Kind regards,

Silvija Gottesman, MD

#dermpathJC April 2018 summary:

#dermpathJC April 2018:

Thursday, April 26th, 9pm EST

Article discussed: Melanocytes Pattern in the Normal Nail, with Special Reference to Nail Bed Melanocytes

Authors: Perrin, Christophe, MD, Michiels, Jean-F., MD, Boyer, Julien, MD, Ambrosetti, Damien, MD

American Journal of Dermatopathology, 2018;40(3):180-184.

Temporary open access available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.13085

Summary author: Silvija P. Gottesman, MD (@SGottesmanMD)

 

Journal Club Summary:

For this month’s journal club we focus on an excellent study that helps define normal melanocytic density in different parts of the nail (nail bed, proximal nail fold, and the nail matrix).

Pigmented nail lesions are divided in three defining categories: melanocytic activation AKA “melanotic macule of the nail unit (melanotic pigmentation of the matrix epithelium without any increase in the density of melanocytes), melanocytic proliferation (lentigo simplex & nevus of the nail matrix), and nail melanoma.

The melanocyte density is a helpful parameter in the distinction of melanotic macule & nail melanoma. Less than 30 melanocytes/mm favor a benign lesion, whereas more than 40 melanocytes/mm favors melanoma. Caveat: some nail melanomas can be low density, and we must rely on other histologic features.

Below is an image depicting a longitudinal section of the nail unit apparatus. Where DPNF is the dorsal proximal nail fold and the Eponychium is the ventral portion of the proximal nail fold. Beyond the proximal nail matrix is the distal nail matrix and then is the nail bed (not depicted in the image here).

Picture1

Density of nail epithelium melanocytes:

– Nail eponychium (ventral proximal nail fold): between 0 and 5 melanocytes per mm, restricted to the basal cell layer.

– Nail matrix: between 4 and 14 melanocytes per mm, in the basal and suprabasal layers.

– Nail bed: between 0 and 5 melanocytes per mm, also restricted to the basal layer.

Dr Gardner  (@JMGardnerMD) shared a diagnostic pearl from Dr Beth Ruben: “unlike acral nevi where pagetoid spread can be ok, pagetoid spread is a bad sign in a nail melanocytic lesion.”

HMB45 and Melan-A are more sensitive markers than tyrosinase and MITF in the detection of intraepithelial nail melanocytes. But since MITF is a nuclear marker, it may be helpful in judging the size and shape of the nuclei of nail melanocytes.

Picture2

MITF (nuclear stain) in action. Small nuclei of nail melanocytes highlighted. And positive cytoplasmic staining of mastocytes in the surrounding dermis as a positive control.

This paper analyzed nail epithelium from 5 Caucasian cadavers. My understanding is that racial differences is not due to differences in the number of melanocytes, but rather the size, distribution, and number of melanosomes (all races have SAME melanocyte density). The one exception is sun damaged skin of elderly Caucasian patients, where MORE melanocytes in sun exposed skin (solar hyperplasia) is seen as compared to darker skinned patients.

For more discussion about Nail Pathology please check out Dr Gardner’s interview with Dr Beth Ruben (@BethRubenMD), a world famous dermatopathologist and nail pathologist. YouTube link: https://youtu.be/_pwNak_CzUc

Bonus: Dr Ruben’s processing techniques for nail unit tissue: make the lab aware the specimen is delicate and may also contain hard keratin. Nair (NaOH/CaOH) solution can be used prior to processing to soften the specimen. Cedarwood oil may be helpful in processing specimens as well. Soaking the block prior to cutting the tissue after processing can minimize knife trauma. Albumin can help sections stay on the slide.

 

Looking forward to next month’s journal club,

Kind regards,

Silvija P. Gottesman, MD

 

 

 

 

#dermpathJC March 2018 summary:

#dermpathJC March 2018:

Thursday, March 22nd, 9pm EST

Article discussed: Nuclear and cytoplasmic features in the diagnosis of Clark’s nevi

Authors: Valdebran M, Bandino J, Elbendary A, Gad A, Arudra KC, Feraudy S, Elston DM.

Journal of Cutaneous Pathology, 2018;45(3):204-207.

Temporary open access available at: https://onlinelibrary.wiley.com/doi/abs/10.1111/cup.13085

Summary author: Silvija P. Gottesman, MD (@SGottesmanMD)

 

Journal Club Summary:

Study by Elston et al, looked at 100 Clark’s nevi and 84 melanomas for the presence of 14 various cytologic features. Cases from special sites, dysplastic nevi with severe atypia, and cases with inadequate material were excluded. In a way, controversy was avoided by looking at dysplastic nevi with mild and moderate atypia versus melanoma. For many pathologists, distinguishing typical non-severe Clark’s nevi from melanoma is not too difficult. Would have appreciated a discussion on really hard cases and how those compare to melanoma. But in those cases, it is probably best to proceed with molecular testing for a definitive answer.

14 different cytologic features were evaluated, definitions summarized in the table below.

Clarks1

Clark’s nevi lack mitotic figures, abnormal mitotic figures, they lack multiple nucleoli and for the most part have either absent or inconspicuous nucleolus. High nuclear to cytoplasmic ratio did not distinguish between Clark’s nevi and melanomas. Dusty cytoplasm and solid hyperchromasia is also equally seen in Clark’s nevi and melanomas.

Clarks2

When present in >20% of the melanocytes: pleomorphism with enlarged nucleus, notching and mitotic figures, peppered moth chromatin, multiple nucleoli prove helpful features in diagnosing melanomas.

Clarks3

Many pathologists make the diagnosis of Clark’s nevi based on architecture and they use the nuclear atypia for grading of the lesion.

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If too many categories are used, it makes it difficult to decide on a more standardized management. Some pathologists like two tier grading (mild and severe atypia, yet 42% of pathologists (number from a poll during this journal club) use hybrid categories for grading, such as mild to moderate and moderate to severe. There are some Clark’s nevi that have no atypia and several pathologists agree.

Screen Shot 2018-03-31 at 10.56.20 AM

An algorithm for treatment of dysplastic nevi based on cytologic atypia:

Mild atypia = observe

Mild to moderate = observe

Moderate, and “margins appear free” = observe

Moderate, and present at lateral margins = excise

Moderate to severe = excise

Severe = excise

 

It was asked during the discussion if nevi get a grade of atypia for the epidermal component and for the dermal component. A true pearl from the discussion from Dr Joseph Susa (@CutisViaLux) shared word for word “It’s one nevus. It gets one grade. It will be treated one way by the clinician. ” Thank you Dr Susa!

 

For closing thoughts, I will leave you with the “dysplastic” nevus article, a topic so neatly summarized by Dr . He too proposes a two tier grading system. Full article at http://dermpath.com/blog/counterpoint-dysplastic-nevus/

 

Join us next month to learn about nail pathology and how to distinguish normal versus abnormal number of melanocytes.

 

Kind regards,

Silvija Gottesman, MD

#dermpathJC February 2018 Summary:

#dermpathJC February 2018:

Thursday, February 22nd, 9pm EST

Article discussed: Pityriasis lichenoides-like drug reaction: A clinical histopathologic study of 10 cases

Authors: Magro C, Guo R, Nguyen G, Tsang H, Momtahen S.

Dermatology Online Journal, 2017;23(11).

Open access article, PDF available at: https://escholarship.org/uc/item/7xd8j71z

Summary author: Silvija P. Gottesman, MD (@SGottesmanMD)

 

Journal Club Summary:

Drug eruptions are seen commonly in #dermpath practice and can have different histologic patterns: dermal hypersensitivity pattern with superficial and deep perivascular and interstitial lymphoeosinophilic infiltrate, another pattern with interface dermatitis and necrotic keratinocytes, subcorneal pustulosis as in drug induced acute generalized exanthematous pustulosis etc.

Today’s journal club discussion was regarding an uncommon pattern: PLEVA-like drug eruption.

In children, pityriasis lichenoides et varioliformis acuta (PLEVA) most commonly arises secondary to an infection: Toxoplasma, viruses, S. aureus, Group A beta-hemolytic streptococci. Pediatric patients with PLEVA typically have a benign course and the lesions resolve within few months with topical steroids and phototherapy. First-line treatment for pediatric patients should include both oral erythromycin and narrowband ultraviolet B phototherapy (Geller L, Antonov NK, Lauren CT, Morel KD, Garzon MC. Pityriasis Lichenoides in Childhood: Review of Clinical Presentation and Treatment Options. Pediatr Dermatol. 2015;32(5):579-92.).

The journal club article was interesting however the major limitation that it was retrospective and drug association was made after the fact. Clinically, the lesions depicted in this paper did not look typical for PLEVA, rather more in line with Pityriasis lichenoides chronica (PLC). Clinical images of the remaining 9 cases were not shown.

Screen Shot 2018-03-14 at 9.50.35 PM

Pityriasis lichenoides-like drug reaction histology findings are identical to that of PLEVA. Most common drugs involved were antidepressants and statins. Skin lesions appeared 2 weeks to a few months after drug administration.

Screen Shot 2018-03-14 at 9.50.54 PM

Authors classify PLEVA-like drug eruption as a T-cell dyscrasia, despite no T cell gene rearrangement detected. Only 2 out of 9 cases were tested. Perhaps as more cases are reported in the future, a TCR result can be included for all to see if truly such a connection exists. A question to keep in mind: Is it clear that PLEVA has a risk of transformation to mycosis fungoides (MF)? Or is it MF all along that was not histologically diagnosable?

See you all next on 03/22/2018 at 9pm EST for another great journal club.

 

Thank you,

Silvija Gottesman, MD

#dermpathJC January 2018 Summary:

#dermpathJC January 2018:

Thursday, January 25th, 9pm EST

Article discussed: Primary Cutaneous Perivascular Epithelioid Cell Tumor (PEComa):  Five new cases and review of the literature.

Authors: Lauren N. Stuart, Russell G. Tipton, Michael R. DeWall, Douglas C. Parker, Christina D. Stelton, Annie O. Morrison, Landon W. Coleman, Scott W. Fosko, Claudia I. Vidal, Maria Yadira Hurley, Amy H. Deeken, Jerad M. Gardner

Journal of Cutaneous Pathology, 2017;44:713-721.

Open access article, PDF available at:  http://onlinelibrary.wiley.com/doi/10.1111/cup.12972/epdf

Summary author: Dr. Amy H. Deeken (@AmyHDeekenMD).

 

Journal Club Summary:

Perivascular Epithelioid Cell tumor (aka PEComa) is a rare mesenchymal clear cell neoplasm with a diverse nomenclature including: angiomyolipoma, lymphangiomyomatosis, clear cell tumor of the lung, and myomelanocytic tumor of the falciform ligament.

When these neoplasms occur primarily in the skin, they begin as a painless, irregular non-pigmented papule/nodule or plaque on the extremities (most commonly on the leg in this series).   Because these neoplasms are so uncommon, the authors include pictures of their five cases for illustrative purposes of the variety of presentations and histologic variability.

1

Photo Credit:  Dr. Wayne Breer

2

Photo Credit:  Dr. Amy Deeken

3

Photo credit:  Dr. Lauren Stuart

 

There is no accepted normal cell counterpart.  The tumor is comprised of epithelioid cells with bland nuclei, clear or granular eosinophilic cytoplasm, in a nested and trabecular pattern.  The clear cells characteristically stain positively with melanocytic and smooth muscle markers.  However, primary cutaneous location is associated with a much higher likelihood of negative smooth muscle stains (almost 50%).  When they are positive, the staining pattern is often patchy or focal with <5% of cells staining in some studies.  The most reliable positive marker was SMA (42%) followed by desmin (30%).  The other marker of interest in the discussion was CD 10.  This stained positive in all three cases in which it was tested.  This unexpected finding was discussed as it relates to the differential diagnosis which could lead to the mistaken diagnosis of metastatic renal cell carcinoma.  Other IHC results were included in this informative table which also includes the most common differential diagnoses considered in these lesions –

4

Molecular testing of PEComas arising from other locations reveal positive results for TFE3 gene fusions and TFE3 immunohistochemical staining.  However, these molecular alterations are lacking in the primary cutaneous form of the disease.  This observation in association with unconventional immunostain patterns for smooth muscle suggests the possibility of more than one subtype in the PEComa family of neoplasms.  The mTOR pathway has been suggested to be a contributing factor the development of the primary cutaneous PEComa.

This is a rare lesion, and the clinical behavior has not been entirely elucidated.  Most studies list small sample size as a limiting factor in their analysis.  Primary cutaneous PEComas have generally exhibited benign behavior, the cases included in this series are no exception.  There was discussion among the #dermpathJC participants regarding optimum surgical therapy.  The study’s principle author, Dr. Jerad Gardner, advocated for conservative excision to negative margins due to the low volume of data regarding their clinical behavior and rare case reports of metastatic lesions.

 

In short –

#DermPath JC #pearl of the evening from Dr, Joseph Susa, @CutisViaLux – “When people start bringing up metastatic balloon cell melanoma with unknown primary, it’s time to start thinking of PEComa”

 

See you all next on 02/22/2018 at 9pm EST for another great journal club.

 

Thank you,

Silvija Gottesman, MD

#dermpathJC December 2017 Summary:

#dermpathJC December 2017:

Thursday, December 28th, 9pm EST

Article discussed: Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type. Diagnostic Considerations

Authors: Alexandra Hristov.

Archives of Pathology and Laboratory Medicine, 2012; 136: 876–881.

Open access article, PDF available at: http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2012-0195-RA?code=coap-site

Summary author: Dr. Silvija P. Gottesman (@SGottesmanMD).

Journal Club Summary:

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type (PCDLBCL-LT), was recognized 20 years ago as a unique diagnostic entity, with exclusive involvement of the leg, intermediate prognosis and a diffuse dermal infiltrate of large B-cells.

PCDLBCL-LT – involves lower legs of women, F:M ratio is 2-4 : 1, median age 70s. However, 10-20% of the time, other parts of the body may be involved. Most common spread is to lymph nodes, bone marrow and the CNS. 50% survival at 5 years.

PCDLBCL-LT histology findings: grenz zone, diffuse sheets of large B-cells in the dermis, large centrocytes, centroblasts and immunoblasts. Mitotic figures are easily identified. T-cells are sparse.

Model of LC transformation

PCDLBCL-LT markers: B-cell (CD19, CD20, CD22, CD79a, PAX-5), also BCL2, IRF4/MUM1 and FOXP1. This IHC profile may also be seen in other diffuse large B-cell lymphomas that involve the skin secondarily.

Screen Shot 2017-12-28 at 7.44.38 PM

WHO notes 10% of PCDLBCL-LT do not express BCL2 or IRF/MUM1. Some classify BCL2- DLBCL of the skin as “primary cutaneous DLBCL, other.”

PCDLBCL-LT also commonly express BCL6, but typically lack CD10. IgM is another sensitive marker but may be difficult to interpret.

Primary cutaneous follicle center cell lymphoma vs EBV diffuse large B-cell lymphoma of the elderly vs Lymphomatoid granulomatosis. Figure below:

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PCDLBCL-other should be used to describe rare cases of primary cutaneous T-cell and histiocyte-rich large B-cell lymphoma, or cases of intravascular large B-cell lymphoma or plasmablastic lymphoma that are limited to the skin at presentation.

Primary cutaneous follicle center cell lymphoma (PCFCL) – most common primary cutaneous B-cell lymphoma. Affects older adults, men more common than women. Often on head/neck and trunk. Extracutaneous spread, in 10%, to lymph nodes and bone marrow. 95% survival at 5 years.

PCFCL involving the leg tends to have a worse outcome and more likely to express BCL2, MUM1, FOX-P1, and IgM.

Reactive T-cells often prominent in PCFCL and is a helpful feature in distinguishing it from PCDLBCL-LT.

Look for inside out follicles in pcFCL – Neoplastic follicle center cells surrounding small lymphocytes and abutting dermal collagen.

PCFCL – pan B-markers, BCL6, less commonly CD10. Disrupted follicular networks highlighted by CD21, CD23, or CD35. All marginal zone B cells are BCL2+ and BCL6-. Opposite is true for normal follicular B cells and those in pcFCL. If centrocyte like B cells in skin are BCL6+ and BCL2+ consider cutaneous involvement of systemic follicular lymphoma. Strong expression of CD10 and BCL2 is suggestive of cutaneous involvement of a systemic follicular lymphoma. MUM-1 usually negative in pcFCL and positive in pcDLBCL-LT.

EBV can lead to so many odd lymphoid proliferations in immunocompromised. Here are two examples below:

EBV-positive diffuse large B-cell lymphoma of the elderly – necrosis is common and a background mixed inflammatory infiltrate may be seen that includes histiocytes and plasma cells. Also BCL6+, CD30+, MUM1+ and some B-cell markers.

Lymphomatoid granulomatosis – skin involvement in 25-50% of patients, >90% will have pulmonary involvement, CNS is common too. Median survival of 2 years. It is angiocentric and angiodestructive, large EBV+ B-cells, necrosis and a mixed infiltrate. DSLpsWqUMAA8CxA

In the words of Dr Deeken: Lymphoma work-up: All of the CD’s and don’t forget the EBV 😉

#hemepath

 

See you all next on 01/25/2018 at 9pm EST for another great journal club.

 

Thank you,

Silvija Gottesman, MD