#dermpathJC May 2020 summary

#dermpathJC May 2020:

Thursday, May 28th, 9 pm EST

Article discussed: Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated

Authors: Juan C. Tardío, Fernando Pinedo, José A. Aramburu, Dolores Suárez-Massa, Ana Pampín, Luis Requena and Carlos Santonja

Temporary open access courtesy of Journal of Cutaneous Pathology: https://doi.org/10.1111/cup.12603

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

Article Summary:

Background: Pleomorphic dermal sarcoma (PDS) is a rare neoplasm sharing pathological features with atypical fibroxanthoma, but adding tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Although its metastatic risk has been estimated to be less than 5%, its real outcome is presently uncertain because of its rarity and to the lack of homogeneous criteria used in reported cases.

Methods: Retrospective clinicopathological study of 18 cases of PDS.

Results: The lesions presented as tumors or plaques (size: 7–70mm) on the head of elderly patients (median: 81 years), without a gender predominance. Histopathologically, they consisted of spindle cells arranged in a fascicular pattern, containing pleomorphic epithelioid and giant multinucleated cells in varying proportions, and usually exhibiting numerous mitotic figures and infiltrative tumor margins. No

Immunoexpression for cytokeratins, S100 protein, desmin or CD34 was observed. Necrosis and venous invasion were found in three tumors each (17%). Follow-up was available in 15 cases (median: 33 months). Three patients (20%) had local recurrences, all with incomplete primary surgical resections. Three patients (20%) developed distant metastases in the skin, regional lymph nodes and/or lungs and died from the disease.

Conclusion: Our data suggest that PDS may be a more aggressive neoplasm than previously estimated.

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Journal Club Summary:

  • Atypical fibroxanthoma (AFX) is most commonly found on sun-exposed skin of the elderly, particularly the head
  • Histologically characterized by a mixture of spindle, epithelioid, and multinucleated giant cells with marked pleomorphism and many mitoses
  • Architecture may be fascicular, storiform, or haphazard
  • Immunohistochemistry is negative for cytokeratins (CK), S100, desmin, and CD34 while positive for vimentin, CD10, CD99 and variably CD68 and p53
  • 42, a marker of normal and neoplastic follicular dendritic cells (FDC), was shown to be positive in 50% of cases in this study and were negative for other FDC markers such as CD21 and CD23
    • Unfortunately, CNA.42 is positive in AFX, leiomyosarcomas, melanomas and carcinomas (unpublished observations by the authors)
  • According to the WHO, necrosis, invasion into deep subcutis or underlying fascia or skeletal muscle, lymphovascular invasion, or perineural invasion do not constitute a diagnosis of AFX
  • The name “pleomorphic dermal sarcoma” (PDS) has been proposed for such lesions, formally known as cutaneous malignant fibrous histiocytoma (MFH)
  • Confusion has ensued due to the lack of understanding about the true behavior of these lesions as well as some use of both terms as synonyms in the literature
  • Although controversy exists about using different terms for naming members of the same disease spectrum, the differences in clinical behavior between AFX and PDS merits an unambiguous message to the clinicians that is better guaranteed, in the authors opinion, distinguishing them by nomenclature
  • Clinical behavior is indolent with rare recurrence and even rarer metastasis (5% based on limited data and classification criteria)
  • Combining data from this study and a previous study by Miller et al, PDS seems to have a more aggressive clinical behavior, estimated to be 14% metastasis rate, including the skin, regional lymph nodes, and the lungs
  • At least 3 patients died from PDS (7%)
  • When metastasis has occurred, some cases infiltrate beyond the subcutis, contain necrosis, or contained no histopathologic or immunohistochemical information
  • A diagnosis of PDS should be reserved for tumors in sun-damaged skin of the elderly because they are extremely rare in non-sun-damaged skin, if they exist at all
  • TERT promoter mutations with an ultraviolet signature in 76% of PDS supports this view
  • Deletions in chromosomes 9p and 13p are seen in PDS at a similar frequency as AFX and undifferentiated pleomorphic sarcomas (UPS)
  • UPS shows H-ras and K-ras mutations (absent in AFX) and overall, more genetic alterations in complete genomic hybridization (CGH) studies
  • The authors retrospectively studied 18 PDS with emphasis on outcome and the differential diagnosis
  • Out of 12 previously classified PDS/cutaneous MFH and 112 AFX, the inclusion criteria for the series were as follows:
    • Spindle cell and/or pleomorphic dermal-based mesenchymal neoplasms without morphologic or immunohistochemical features diagnostic of any distinct entity
    • Lack of CK, S100 protein, desmin and CD34 expression
    • Invasion of at least the deep subcutis and/or tumor necrosis and/or vascular or perineural infiltration
  • 9 of the 12 PDS were excluded because primary subcutaneous sarcoma infiltration into the dermis could not be ruled out and expression of one or more of the above IHC
  • 15 of the 112 AFX cases were reclassified as PDS making a total of 18 PDS
  • M:F ratio was 1:1 (in contrast to previously reported male predominance)
  • Mean age was 81
  • Patients either had prior trauma or carcinomas in the same vicinity or immunosuppression due to rheumatoid arthritis, renal disease, or their age
  • Clinically they were described as either plaques or tumors, 10 of which were ulcerated
  • Mean size was 22mm with a range from 7-70mm
  • 13 cases showed an asymmetric silhouette and 15 cases showed an infiltrative border
  • Grenz zone, epidermal collarette and epidermal connection were absent in all cases
  • Except in cases with a conventional carcinomatous, melanocytic or sarcomatous component, sarcomatoid carcinoma, melanoma, leiomyosarcoma and angiosarcoma are mainly differentiated from PDS by their immunohistochemical (IHC) features
  • Sarcomatoid carcinoma will stain for cytokeratins, especially high molecular weight, and also p63 and EMA but can also be seen in PDS which makes them less useful
  • There will usually be numerous S100+ dendritic cells in PDS but never the neoplastic cells which helps differentiate PDS from melanoma, which will also likely have a conventional or in situ component
  • Leiomyosarcoma will have desmin and smooth muscle histologic features with marginated fascicles and characteristic elongated blunt-ended nuclei with fibrillary cytoplasm
  • Angiosarcoma has a similar site predilection to PDS, hemorrhage, and is positive for CD31, but is also positive for CD34 and ERG as well as a different clinical appearance with large ill-defined bluish, bruise-like patches that evolve into elevated plaques
  • Dermatofibrosarcoma protuberans (DFSP) is more common in younger patients on the trunk or proximal extremities and has a lace-like pattern that can mimic PDS along with CD34 positivity, however, DFSP has uniform spindle cells arranged in a monotonous storiform pattern somewhere within the lesion, even if there are MFH areas with loss of CD34, that will aid in the diagnosis of DFSP
  • Atypical and cellular dermal fibrous histiocytomas can have spindle to pleomorphic areas that may resemble PDS with similar lack of specific IHC, but usually present on the extremities of young to middle-aged adults with a Grenz zone and peripheral collagen entrapment that is limited to the dermis or, at most, the superficial subcutis
  • If PDS contains myxoid stroma, these must be distinguished from myxofibrosarcoma which differ in that they are often on the extremities, have a multinodular growth patter, broad spectrum of celluarity to stroma ratio, characteristic curvilinear thin-walled vessels and pseudolipoblasts.

Memorable tweets:

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Until next month #dermpathJC, stay safe!


#dermpathJC April 2020 summary

#dermpathJC April 2020:

Thursday, April 30th, 9 pm EST

Article discussed: Cutaneous carcinosarcoma: a series of six cases and a review of the literature

Authors: Joshua J. Clark, Anneli R. Bowen, Glen M. Bowen, John R. Hyngstrom, Michael L. Hadley, Keith Duffy, Scott R. Florell and David A. Wada

Open access courtesy of Journal of Cutaneous Pathology: https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.12843

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


Journal Club Summary:

  • Coined by Virchow in 1864, the term carcinosarcoma refers to a biphasic malignant neoplasm with epithelial and mesenchymal components which can be seen in virtually every organ
  • In primary cutaneous carcinosarcoma, the most common epithelial components are basal cell and squamous cell carcinomas, whereas the less common include malignant spiradenoma, porocarcinoma, pilomatrical carcinoma, and trichoblastic carcinoma
  • The mesenchymal component includes fibrosarcoma, pleomorphic undifferentiated sarcoma (previously called malignant fibrous histiocytoma), osteosarcoma, chondrosarcoma, and rhabdomyosarcoma
  • Although cutaneous carcinosarcomas are rare, they are likely under-reported due to lack of awareness, tissue sampling variation, and the variety of clinical/histological phenotypes
  • Of the reported cases reviewed, most occurred on sun-exposed areas of the head and extremities with age ranges from 32 to 98 years old, most cases occurring in the 8th and 9th decades of life
  • Male predominance was found to be 1.7:1
  • Recurrence and death were more common from adnexal carcinosarcomas with equal distribution among the various adnexal groups
  • Patients with basal cell carcinosarcoma had longer disease-free survival than those with squamous cell carcinosarcoma
  • The two hypotheses of the origin of carcinosarcoma include a monoclonal carcinoma that undergoes metaplasia with loss of residual epithelial differentiation versus a convergence of two or more distinct progenitor cells
  • Multiple molecular studies of non-cutaneous carcinosarcomas favor a monoclonal cell population with differentiation into both epithelial and mesenchymal components
  • Basal cell carcinosarcoma has been shown to be related to sun damage with mutations in PTCH1, p53, p63, and p13 genes
  • Squamous cell carcinosarcoma has been shown to have point mutations and deletions in the TP53 gene
  • The main histologic differential diagnosis of malignant biphasic neoplasms includes sarcomatoid carcinoma, malignant mixed tumor, biphasic synovial sarcoma, and malignant peripheral nerve sheath tumor
    • Sarcomatoid carcinoma (spindle-cell squamous carcinoma) = malignant spindle cells with some degree of typical squamous cell carcinoma which can be proven with immunohistochemistry (IHC) for keratins and/or p63 by the spindle cells
    • Biphasic synovial sarcoma = uncertain histogenesis; extremities; young adults; epithelial cells in cords/nests/glands with admixed cellular, monotonous spindle cell proliferation; confirmed with TLE1, EMA, and/or cytokeratin as well as t(X;18) translocation
    • Malignant mixed tumors of the skin = contain carcinoma admixed with benign myxoid or chondroid proliferations; may be S100+
    • Malignant peripheral nerve sheath tumor (MPNST) = rarely can have mucin-producing glands with cuboidal/columnar cells admixed with malignant spindle cells that otherwise fits criteria for the typical MPNST
  • Three diagnostic criteria have been proposed for primary cutaneous carcinosarcoma
    • Clearly defined dual neoplasm with explicit characterization via histology and IHCs
    • Exclusion of metastasis from other sites
    • Exclusion of sarcomatous stromal changes around otherwise normal stroma of a carcinoma
  • There is a lack of criteria to differentiate squamous cell carcinoma with sarcomatoid differentiation from cutaneous carcinosarcoma
  • Management of cutaneous carcinosarcoma depends on the clinical and histologic features
    • The epithelial component correlates with metastasis
      • Basal cell carcinosarcoma = low-risk (2%)
      • Squamous carcinosarcoma and adnexal carcinosarcoma = (12-50%)
    • Tumor size, recent growth, metastases, and tumor chronicity may also affect management but are limited in number for definitive recommendations

Memorable Tweets:

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Until next month #dermpathJC, stay safe!

#dermpathJC March 2020 summary

#dermpathJC March 2020:

Thursday, March 26th, 9 pm EST

Article discussed: Angiosarcoma, Radiation-Associated Angiosarcoma, and Atypical Vascular Lesion

Authors: David R. Lucas

Open access courtesy of Archives of Pathology and Laboratory Medicine: https://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165-133.11.1804

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


Article Abstract:

Angiosarcoma, one of the least common sarcomas, has become increasingly important because of its association with radiation therapy, especially for breast cancer. Most are sporadic, presenting as cutaneous tumors in the scalp/face of elderly patients. However, angiosarcoma has a wide anatomic distribution including soft tissue, visceral organ, and osseous locations. Predisposing conditions include environmental exposures to chemical or radioactive sources. Radiation-associated angiosarcoma typically presents as a cutaneous tumor several years posttherapy. The latency for radiation-associated mammary angiosarcoma is relatively short, sometimes less than 3 years. Atypical vascular lesion refers to a small, usually lymphatic-type vascular proliferation in radiated skin. Although most atypical vascular lesions pursue a benign course, they recur and very rarely progress to angiosarcoma. Distinguishing this lesion from well-differentiated angiosarcoma in a biopsy can be challenging, especially because areas indistinguishable from atypical vascular lesion are found adjacent to angiosarcoma. Recently, vascular-type atypical vascular lesion, which resembles hemangioma, has been described, thus expanding the definition of this entity.


Journal Club Summary:

Angiosarcoma general points:

  • 1% of soft tissue sarcomas
  • Associated with radiation therapy, most often breast cancer
    • Also associated with chronic lymphedema, toxins (i.e. vinyl chloride), and foreign bodies (i.e. A/V fistulas)
  • Usually presents as sporadic cutaneous tumor on scalp/face of elderly
  • Reported in every anatomic site
  • Bruise-like area that ulcerates or becomes nodular
  • Often have smaller satellite lesions peripherally
  • Clinically aggressive with high morbidity, regardless of grade
    • Prognosis in sporadic cutaneous angiosarcoma correlates with high- and low- risk groups on the basis of age, epitheliod histology, necrosis, and tumor depth
  • Deep tumors can be hemorrhagic spongelike or microcystic with necrosis
  • Well-differentiated lesions can be deceptively bland, but will have some combination of hyperchromasia, mild pleomorphism, prominent nucleoli, mitotic figures, multilayering, and/or dermal collagen entrapment forming intraluminal papillary structures
  • Surgical margins may be obscured by atypical lymphatic/capillary proliferations
  • Moderate/poorly differentiated types will often have heterogeneous cytoarchitectural features
    • Some combination of epithelioid, spindled, or pleomorphic cytology
    • Some combination of vasoformative, sieve-like, kaposiform, or solid architecture
  • Undifferentiated angiosarcoma will need immunohistochemistry to confirm the diagnosis
    • CD31 = single best marker with high sensitivity and specificity
      • Diffuse, intense staining with membranous accentuation
      • Can be hard to interpret due to background blush, staining macrophages, and low-level expression in other tumor types
    • CD 34 and factor VIII = present in most angiosarcomas but not reliably in poorly differentiated
    • Cytokeratin pitfall = found in 35% of cases in one study (especially epithelioid angiosarcoma) although usually focal


Radiation-associated angiosarcoma

  • Clinically and morphologically similar to sporadic angiosarcoma
    • Latency is shorter for breast angiosarcoma
      • 5-7 years on average
      • Significant occurrence in less than 3 years which questions the 3-year rule
    • More often cutaneous than sporadic angiosarcoma
      • Erythematous plaque/patch/nodules with edema
      • Diffuse, multifocal, and extensive involvement of the breast is common
      • Median size = 7.5 cm


Atypical Vascular Lesion (AVL):

  • Benign course; can recur; rarely progress to angiosarcoma
  • Tendency to develop further lesions, commonly AVLs
  • Present as 1 or more small, flesh-colored papules or erythematous patches arising in radiated skin
  • Histologically difficult to distinguish from well-differentiated angiosarcoma in a biopsy
  • Often resemble lymphangiomas
    • Well-demarcated proliferation of thin walled, dilated, interanastomosing channels without erythrocytes
    • Lined by attenuated or hobnail endothelial cells without atypia
  • Can resemble lymphangioendothelioma, lymphangioma circumscriptum, or both within the same lesion
  • Most are limited to the superficial and mid dermis
  • Current recommendations are to completely excise and follow for recurrence

Vascular-type AVL

  • First described in 2005 with 3 cases that resemble lobular capillary hemangioma in mammary skin after radiation
    • All 3 cases developed angiosarcoma
  • In 2008, 8 more cases were described where only one developed angiosarcoma

It is suggested that vascular-type AVL is more likely to progress to angiosarcoma than the more common lymphatic-type AVL


Memorable tweets:



Stay safe my friends, and we will see you next month for another dermpath journal club,


With love,


#dermpathJC January 2020 summary

#dermpathJC January 2020:

Thursday, January 23rd, 9 pm EST

Article discussed: Invisible dermatosis, disgnostic discrepancy between the general pathologist and dermatopathologist

Authors: Ahmed Alhumidi, Najd Alshamlan, Mona Alfaraidi, Khaled Mohajer

Temporary open access courtesy of Journal of Cutaneous Pathology at: : https://onlinelibrary.wiley.com/doi/pdf/10.1111/cup.13554

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

Journal Club Summary:

  • Invisible dermatoses are those that have subtle histologic features but have been biopsied because of obvious clinical lesions.
  • Often, a diagnosis of no significant pathological changes or nonspecific findings will be made by a general pathologist.
  • 81 total cases were reviewed over the past 15 years where general pathologists, with experience ranging from 5-20 years, made one of the following diagnoses:
    • No specific diagnosis
    • No significant pathologic changes
    • Minimal pathologic changes
  • These cases were reviewed retrospectively and blindly by a dermatopathologist trained at a reputable center in the United States with 5 years of experience in dermatopathology.
  • Out of 81 total cases, 43 (53%) were found to have a specific diagnosis while the remaining 38 (46.9%) remained non-specific. Of the nonspecific cases, 15 (39.47%) were due to inadequacy of the specimen.
  • This study aims to highlight the diagnostic challenges of invisible dermatosis, the importance of clinicopathologic correlation, biopsy adequacy/preparation, and histochemistry.
  • Conditions that are likely to receive a nonspecific diagnosis by a general pathologist include:
    • Becker’s melanosis
      • Clinically pigmented patches
      • Shoulder, back, or chest
      • Histologically – regular elongation of the rete ridges with basal hyperpigmentation
    • Spongiotic dermatitis – intercellular epidermal edema
      • Eczema
      • Id reaction
      • Pityriasis rosea
      • Pityriasis alba (children, hypopigmented patches that can mimic mycosis fungoides)
      • Many others
    • Pigmented purpuric dermatosis (extravasated red blood cells and hemosiderin-laden macrophages)
      • Progressive pigmentary dermatosis of Schamberg (subtle deposits and scant inflammation)
      • Purpura annularis telangiectodes of Majocchi
      • Eczematoid-like purpura of Doucas and Kapentanakis
      • Pigmented purpuric dermatitis of Gougerot and Blum
    • Increased dermal mucin (often subtle, can use Alcian blue and colloidal iron stains)
      • Generalized myxedema
      • Pretibial myxedema
      • Lichen myxedematosus
      • Papular mucinosis
      • Reticular erythematous mucinosis
      • Self-healing juvenile cutaneous mucinosis
      • Scleroderma
    • Pityriasis/tinea versicolor (caused by Malassezia furfur)
    • Acute generalized exanthematous pustulosis (AGEP)
    • Mycosis fungoides (cutaneous T-cell lymphoma)
    • Urticaria (if resolves within 24 hours; if chronic, suspect urticarial vasculitis)
    • Primary cutaneous amyloidosis (HMWCK+)
    • Vitiligo
    • Telangiectasia macularis eruptive perstans (TMEP; mastocytosis, highlighted by Giemsa, toluidine blue, and CD117)

jan1 This pie chart illustrates the types of diagnoses were rendered by dermatopathologists when they reviewed pathology slides without significant pathology or no diagnosis report.


Memorable Tweets:


Differential diagnosis of invisible dermatoses. A mnemonic by @SGottesmanMD.Diqgo74U0AAz3dh



Thank you so much for attending #DermpathJC and for reading this summary.

We are always here for you and your dermatopathology learning,



#dermpathJC December 2019 summary

#dermpathJC December 2019:

Thursday, December 5th, 9 pm EST

Article discussed: Dermatologic Urgencies and Emergencies: What Every Pathologist Should Know

Authors: Mallory S. Abate, MD; Laura R. Battle, MD; Ashley N. Emerson, MD; Jerad M. Gardner, MD; Sara C. Shalin, MD, PhD

Open access courtesy of Archives of Pathology at: https://www.archivesofpathology.org/doi/10.5858/arpa.2018-0239-RA

Summary prepared by: Mitul B. Modi, MBBS, MD (@MitulModiMD)


Journal club summary:


Dermatologic diseases with high morbidity can occur in the inpatient setting. In these circumstances, bedside skin biopsy, although challenging could be the most important guiding tool for accurate assessment, especially for pathologists not experts in dermatopathology. This unique review represents a collaborative opinion from both dermatology and a dermatopathology view.


Herein, with this article authors are providing a reference guide on dermatologic urgencies and emergencies, focusing on diagnostic pearls, pitfalls, and commonly encountered practice scenarios. The key diseases focused in this article are angioinvasive fungal infections, Stevens-Johnson syndrome/toxic epidermal necrolysis, staph-scalded-skin syndrome, acute graft-versus-host disease, bullous pemphigoid, calciphylaxis, Sweet syndrome and its histiocytoid variant, pyoderma gangrenosum, and leukocytoclastic vasculitis, as well as those in their clinical and histopathologic differential.


High-yield points:

  • Rapidly progressive in immunosuppressed or trauma patients with high mortality.
  • Hematoxylin-eosin (H&E) reveals fungal hyphae in the dermis and/or vessels +/− epidermal and/or dermal necrosis.
  • Periodic acid–Schiff (PAS) or Gomori methenamine silver (GMS) is performed in all suspicious cases.
  • Speciation cannot be performed based on histopathology alone.




High-yield points for SJS and TEN:

  • Life-threatening skin disorder with full-thickness epidermal sloughing of the skin and mucous membranes.
  • First step in treatment is immediate identification and withdrawal of causative drug.
  • Can mimic erythema multiforme (EM) histologically, requiring clinical differentiation.
  • Differentiated from SSSS both clinically and histologically because of the more superficial level of blistering in SSSS.




High-yield points for aGVHD:

  • Nonspecific morbilliform eruption in HSCT patients.
  • Hematoxylin-eosin reveals vacuolar interface dermatitis.
  • In early stages it can be histologically indistinguishable from other common rashes like viral exanthems or drug eruptions in the posttransplant period.



High-yield points for BP:

  • Subepidermal blistering disease most commonly seen in the elderly.
  • Characterized by tense bullae clinically, which correlate to cleavage along the basement membrane zone histologically.
  • Definitive diagnosis is made by immunofluorescence studies.



High-yield points for calciphylaxis:

  • Tissue ischemia that develops as a serious complication in patients with end-stage renal disease (ESRD) on dialysis.
  • Hematoxylin-eosin reveals thrombotic vasculopathy in small (often subcuticular) vessels, with basophilic calcium deposits in the deep dermis and subcutis, associated inflammation, and/or tissue necrosis.
  • Von Kossa or alizarin red should be performed in all suspicious cases.



High-yield points for Sweet syndrome:

  • Erythematous “juicy” papules on the head, neck, and upper extremities.
  • May be associated with underlying malignancy, infection, or medications.
  • Hematoxylin-eosin reveals marked papillary dermal edema with abundant neutrophils.
  • Despite clinical presentation and histopathology that may suggest an infectious etiology, all infectious workup will be negative.
  • Excellent response to corticosteroids.
  • A diagnosis of histiocytoid Sweet syndrome should be made with caution and leukemia cutis must be excluded.



High-yield points for Histiocytoid Sweet syndrome:

  • Indistinguishable from classic Sweet syndrome clinically
  • histiocytoid Sweet syndrome is histologically distinct and characterized by an infiltrate of mononuclear cells that have a histiocytic appearance;
  • histologically mimicker of leukemia cutis



High-yield points for PG include the following:

  • A “neutrophilic dermatosis” that presents with rapidly progressive skin ulcerations.
  • Commonly misdiagnosed, which can result in devastating tissue loss.
  • Histology is nonspecific and the inflammatory infiltrate can vary with location of biopsy and duration of lesion.
  • Infection by bacteria, fungi, or acid-fast bacteria must be excluded by either special stains, microbial cultures, molecular techniques, or a combination of these.




High-yield points for cutaneous LCV include the following:

  • Represents a distinct histologic inflammatory pattern affecting small vessels of the dermis.
  • Corresponds to the clinical diagnosis of cutaneous small vessel necrotizing vasculitis and classically manifests as palpable purpura.
  • Can be seen in a variety of primary vasculitic dermatoses or as a secondary finding in nonvasculitic dermatoses; clinicopathologic correlation is required.



  • This article has highlighted the pivotal role that pathologists/dermatopathologists play in dermatologic urgencies and emergencies. This, in turn, can be helpful in providing accurate histologic diagnoses with improved patient care in a timely manner.
  • This review thus serves as a practical reference guide for any pathologist while working up a rush inpatient skin biopsy. In emergency cases and scenarios, an initial discussion and an open line of communication between a dermatologist with the pathologist is important for providing a histologic diagnosis in a timely manner.
  • As soon as the slides have been processed, it is helpful to hear the pathologist’s initial impression of the biopsy as well as of any positive, negative, and pending stains. This way of continued conversation with the dermatologist can help narrow the differential diagnosis and ultimately help the pathologist/dermatopathologist to arrive at the diagnosis.
  • The takeaway point from this article is that a systemic and collaborative approach yields the best patient outcome, instead of panicking while coming across dermatologic emergencies and urgencies.






Thank you so much for attending #DermpathJC and for reading this summary.

Hope you enjoyed the energy of this journal club,

We are always here for you and your dermatopathology learning,

Happy Holidays and Happy New Year!



#dermpathJC October 2019 summary

#dermpathJC October 2019:

Thursday, October 24th, 9pm EST

Article discussed: Gene expression profiling of lichenoid dermatitis immune‐related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response

Authors:Curry JL, Reuben A, Szczepaniak-Sloane R, Ning J, Milton DR, Lee CH, Hudgens C, George S, Torres-Cabala C, Johnson D, Subramanya S, Wargo JA, Mudaliar K, Wistuba II, Prieto VG, Diab A, Tetzlaff MT

Temporary open access courtesy of Journal of Cutaneous Pathology at: https://onlinelibrary.wiley.com/doi/full/10.1111/cup.13454

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


Journal club summary:

Background: Patients receiving checkpoint inhibitors (CPIs) may develop a number of immune‐related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism underlying the emergence of these irAEs remains poorly understood. The current study aims to determine the unique gene expression profiles and immune composition in LD—irAE.

Study design:

Gene expression profiling on a series of LD—irAE (n = 3) and compared them with a series of sporadically occurring benign lichenoid keratosis (BLK) (n = 3). Profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. IHC analysis was performed. Benign lichenoid keratosis and Lichenoid dermatitis (immune-related adverse event) show indistinguishable histologic features.


Results and discussion:

LD—irAE exhibit upregulation of CD14 mRNA transcripts and TLR as compared with BLK control

Lichenoid dermatitis 2/2 immune-related adverse event exhibits upregulation of CD14 mRNA (a marker of monocyte and co-receptor for TLRs), higher numbers of CD14+ and CD16+ monocytes, downregulation of CD83 (a marker of mature dendritic cells), upregulation of chemotactic molecules, CXCL12 and CCL14.

Representative immunohistochemic stains for CD14, CD16, T‐Bet, Gata‐3, and FoxP3 in benign lichenoid keratosis (BLK) control (left) and LD—irAE (right)


TLRs – Toll like receptors are important mediators of the innate immune system response. Gene profiling of lichenoid dermatitis 2/2 immune-related adverse event bx showed upregulation of TLRs, CD14/TLR signaling pathway and MAPK.

LD—irAE exhibits a Th1 immune profile

The rationale for the statement above is the following:

T‐Bet is a known driver of pro-inflammatory responses (Th1), while GATA-3 is a known driver of anti-inflammatory responses (Th2)  and FoxP3 (forkhead box P3) is a known T regulatory cells marker (Treg).

  • LD-irAE exhibited lower Th2 expression as compared with BLK
  • LD-irAE exhibited higher Th1 expression than Th2 expression overall
  • LD-irAED exhibited lower FoxP3 expression as compared to BLK


  • There is activation of the innate immune response through CD14/TLR signaling pathway in LD—irAE.
  • LD—irAE may be related to checkpoint inhibitor therapy effect on CD14/TLR signaling of CD14+CD16+ monocytes recruited to the skin.
  • Additional immune pathways involved in the development of LD—irAE include activation from skin microbiome, cytokines, and recruitment of CD14+CD16+ monocytes possibly initiate an inflammatory reaction that results in LD (summarized in the diagram below)


Some Highlights from the Evening:



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 September 2019 summary

#dermpathJC September 2019: 


Thursday, September 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).


  • 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).


  • 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 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.


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.

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