Courtney Cruickshank

November 2024 Case Study

Authors: Sapana Desai & Dillon Nussbaum

1. Department of Dermatology, George Washington University School of Medicine and Health Sciences

Patient History

A 65-year-old female with a history of hypertension presents for an intermittently pruritic rash for 11 years that has been unresponsive to topical steroids. On physical examination, there are extensive, well-demarcated, tan to dark brown, erythematous, indurated papules and annular plaques on the abdomen, arms, and lower extremities bilaterally (Figure 1). A punch biopsy was performed (Figure 2, hemoxylin and eosin stain). A colloidal iron stain revealed significant mucin deposition.

Based on the clinical presentation and biopsy findings, what is the next best step in management?

A) Order an antinuclear antibodies (ANA)
B) Perform a potassium hydroxide (KOH) preparation
C) Recommend age-appropriate cancer screenings
D) Perform a Wood’s lamp examination
E) Perform repeat biopsy for direct immunofluorescence

Correct Answer: C

Explanation/Literature Review

Explanation of Correct Answer:  

Given the clinical description and associated pathologic finding of palisading necrobiotic granulomas with mucin deposition, the patient was diagnosed with generalized granuloma annulare (GGA).^1-4 GGA is a variant of granuloma annulare (GA) characterized by more than 10 red to brown, raised, ring shaped dermal plaques, usually in a symmetric distribution.^2,3 GGA is the more extensive variant of GA, which is a benign and often self-limited granulomatous dermatosis that on pathology exhibits dermal necrobiosis, mucin deposition, and palisading or interstitial granulomas. GA can present in five subtypes:

1) Localized GA- represents approximately 75% of all reported cases and presents as well-defined, annular plaques with a circinate configuration, most commonly on the hands and feet;

2) Generalized GA- GGA presents with more than 10 erythematous papules in an annular or arcuate configuration on the trunk and extremities;

3) Subcutaneous GA- presents with deep, firm nodules that resemble pseudo-rheumatoid nodules, most commonly found on the extremities, and seen almost exclusively in children;

4) Patch GA- presents with erythematous, often scaly patches that involve large areas of skin, most commonly on the trunk;

5) Perforating GA- presents with umbilicated papules confined to the trunk and extremities, which subsequently rupture.^1-4

The etiology and pathogenesis of GA is largely unknown, but GA has been associated with hyperlipidemia, diabetes mellitus, and thyroid disease. The prevalence of GA is estimated to be between 0.1% to 0.4%, and the disease can affect individuals of any age, with an increased predilection for women. Although GA can resolve spontaneously, affected areas tend to recur in many patients.

While rare, GGA can present in association with various malignancies, including blood, breast, cervical, lung, prostate, stomach, and ovarian cancer. Therefore, the best next step for patients with GGA is to C) recommend age-appropriate cancer screenings, especially in the context of elderly patients, atypical or widespread presentations, and recalcitrant disease.⁴ The most common malignancy associated with GGA is chronic lymphocytic leukemia and the most common solid organ malignancy is prostate cancer. Malignancy associated GA is most commonly seen in the 7^th decade, whereas localized GA occurs in younger patients more commonly and malignancy associated GA typically resolves after treatment of the associated cancer.^3,4

Explanation of Incorrect Answers:

Dermatomyositis (DM) is an autoimmune inflammatory disease affecting women more commonly than men, with a bimodal peak of incidence between ages 5 and 14 and ages 45 and 65.^5,6 DM is sub-classified into adult-onset disease and juvenile disease (JDM). Serum antinuclear autoantibodies are often present, as are other myositis-specific autoantibodies, and ordering antinuclear antibodies (ANA) may be a useful prognostic indicator in diagnosis and management of DM.⁶

Tinea corporis is a superficial fungal skin infection most commonly caused by trichophyton rubrum, often arising due to factors like excessive heat and humidity, tight clothing, and compromised immunity. Tinea corporis can have a similar annular morphology to GA and should be considered in the differential.⁷ Tinea corporis typically has a significantly shorter history of several weeks, rather than years, and often demonstrates scale along the advancing border, a feature generally absent in GA. Performing a potassium hydroxide (KOH) preparation (Answer B) is a helpful tool to rule out a fungal etiology, particularly in scaly lesions where fungal species  would exhibit septate hyphae under microscopy.⁷

Vitiligo is a chronic autoimmune condition  of melanocytes, resulting in depigmentation that on histology exhibits decreased or complete loss of melanocytes, ⁹ Diagnosis of vitiligo is supported by performing a D) Wood’s lamp examination, which reveals with a peak wavelength of 365nm reveals depigmented areas and helps differentiate vitiligo from other hypopigmentation disorders. Patients with vitiligo can also have other autoimmune diseases, most commonly Hashimoto’s disease.

Bullous pemphigoid (BP) is a chronic vesiculobullous eruption involving antibodies targeting transmembrane proteins. BP manifests as tense bullae on non-mucosal sites, and on pathology reveals subepidermal blisters with eosinophils. BP usually begins with urticarial plaques which tend to have eosinophilic spongiosis on histology. Direct immunofluorescence of BP consists of linear IgG and C3 deposition at the dermal-epidermal junction (Answer E). The morphology and presentation of this patient’s rash are not consistent with BP.

References

1. Bagci B, Karakas C, Kaur H, Smoller BR. Histopathologic Aspects of Malignancy-Associated Granuloma Annulare: A Single Institution Experience. Dermatopathology (Basel). 2023;10(1):95-103. Published 2023 Mar 4. doi:10.3390/dermatopathology10010015
2. Joshi, T., Duvic, M. Granuloma Annulare: An Updated Review of Epidemiology, Pathogenesis, and Treatment Options. American Journal of Clinical Dermatology. January 2022; 23(1): 37-50.
3. Piette, E., Rosenbach, M. Granuloma Annulare: Clinical and Histologic Variants, Epidemiology, and Genetics. Journal of American Academy of Dermatology. September 2016; 75(3): 457-465.
4. Gittler J., Mir, A., Meehan, S., Pomeranz, M. Photodistributed Granuloma Annulare. Dermatology Online Journal. December 2025; 21(12): 13030.
5. O’Connell, K., LaChance, A. Dermatomyositis. New England Journal of Medicine. June 2021; 384(25): 2437.
6. Sugie, K. Dermatomyositis. Brain Nerve. May 2024; 76(5): 635-645.
7. Chong, AH., Kovitwanichkanont, T. Superficial Fungal Infections. Australian Journal of General Practice. October 2019; 48(10): 706-711.
8. Dahir, AM., Thomsen, SF. Comorbidities in Vitiligo: Comprehensive Review. International Journal of Dermatology. 2018; 57(10): 1157-1164.
9. Rork JF, Rashighi M, Harris JE. Understanding autoimmunity of vitiligo and alopecia areata. Curr Opin Pediatr. 2016;28(4):463-469.
10. Image source: The Full Spectrum of Dermatology: A Diverse and Inclusive Atlas

October 2024 Case Study

Authors: Sapana Desai & Trey Lampley

Patient History

A 31-year-old Caucasian female with a history of seasonal rhinitis presents with a lifelong generalized red, scaly, pruritic rash. The patient states that the most noteworthy feature of the rash is the extensive and recurring skin peeling. On physical examination, there are broad, coalescing erythematous polycyclic patches and plaques with peripheral desquamative scale located on her upper extremities, lower extremities, chest, and back (Figure 1.). Results from a 3mm punch biopsy are shown in Figure 2.

A mutation in which of the following genes is responsible for her condition?

A) ATP2C1
B) SPINK5
C) KRT2
D) TGM5
E) HRAS

Correct Answer: B

Explanation/Literature Review

Explanation of Correct Answer:

This patient’s clinical presentation and history coupled with a biopsy characterized by hyperkeratosis, focal hypergranulosis, epidermal acanthosis, and superficial perivascular lymphocytic infiltrate, is indicative of Netherton syndrome.^1-3

Netherton syndrome is a rare, autosomal recessive genodermatosis caused by mutations in the SPINK5 (B) gene, which encodes the serine protease inhibitor LEKTI. Deficiency in LEKTI prompts highly unregulated protease activity of KLK5 and KLK7, resulting in extensive desquamation of the stratum corneum, compromised skin barrier function, and heightened vulnerability to infections and allergic reactions.^1-4 The clinical triad of Netherton syndrome includes: 1) Ichthyosis linearis circumflexa, marked by red, scaly annular plaques with the “text book” serpiginous, double-edged scaling; 2) Trichorrhexis invaginata, a hair shaft abnormality resulting in early broken hairs that appear as “bamboo hair” or “ball and socket” abnormalities under magnification; and 3) A spectrum of atopic disorders, including severe atopic dermatitis, asthma, food allergies, and metabolic imbalances.^2,3 Netherton syndrome first presents in infancy and has no predilection for any race or gender. Although there is no approved treatment, management often includes protective emollients, topical corticosteroids, and off label systemic medications which more recently have included targeted therapies such as dupilumab. Of note, oral retinoids and topical calcineurin should be avoided in Netherton Syndrome. Integrating a multidisciplinary approach, including dermatologists and immunologists, is essential for further optimizing the quality of life for affected individuals.^1-4

Explanation of Incorrect Answers:

Benign familial pemphigus (BFP), also known as Hailey-Hailey disease, is a rare autosomal-dominant genodermatosis caused by mutations in the ATP2C1 (A) gene, which disrupts calcium homeostasis of keratinocytes.^5-7 The resulting dysfunction in desmosomes and cell-cell adhesion elicits impaired keratinocyte adhesion and widespread intraepidermal acantholysis.^5-8 This chronic disease presents with episodic, painful, and pruritic plaques with flaccid vesicles and erosions (often described as stellate). Inguinal folds, inframammary folds, and axillae are the most common locations, and are typically bilateral.⁶ Heat, friction, and trauma are known to worsen active disease.  BFP is usually diagnosed between the third and fourth decades of life. While there are no FDA approved treatments, antimicrobial washes, barrier protectants, and emollients are often used in conjunction with systemic therapies such as off label use of dapsone, oral retinoids, and botulinum toxin A.^7,8

Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant congenital ichthyosis clinically characterized by mild epidermolytic, hyperkeratosis on the limbs and lower trunk with flexural accentuation, intracorneal blistering, and the development of superficially denuded areas of hyperkeratotic skin (Mauserung phenomenon).^9-11 IBS manifests due to mutations in the KRT2 (C) gene. This gene encodes keratin 2, a structural protein crucial for maintaining the integrity of the upper epidermis. This disease can present as early as infancy and can persist into adulthood.  Emollients and mild keratolytic preparations often provide effective therapy and can induce impressive remission.^9,10

Acral peeling skin syndrome (APSS) is a rare, autosomal recessive genodermatosis characterized by shedding of the superficial layers of the epidermis, often accompanied by blister formation. APSS is caused by mutations in the TGM5 (D) gene, which is localized to chromosome 15q15. These mutations inhibit the cross-linking activity of the transglutaminase-5 enzyme. This enzyme is essential for the terminal differentiation of the epidermis and formation of the cornified cell envelop which is crucial for skin barrier integrity.^12,13 Patients with APSS have weakened cohesion of the stratum corneum which leads to the skin peeling that they experience. This painless peeling is typically located on the palmer, plantar, and dorsal surfaces of the hands and feet. Triggers include humidity, occlusion, immersion in water, and friction. APSS is not associated with other systemic symptoms, and treatment focuses on gentle skin care, hydration, and avoiding mechanical trauma.^12,13

Spitz nevi are benign melanocytic lesions that have clinical and pathological features similar to melanoma. Genetic mutations frequently implicated in Spitz nevi include HRAS (E) and BRAF mutations, which activate the RAS-MAPK signaling pathway, promoting melanocyte proliferation. Additionally, fusion genes involving kinases such as ALK, ROS1, NTRK1, or BRAF are identified in a subset of cases, driving tumor development.^14-16 Spitz nevi can usually be monitored, but particularly atypical lesions are often treated with surgical excision due to their pathologic overlap with melanoma.¹⁶

References

1. Stevanovic DV. Multiple defects of the hair shaft in Netherton’s disease: Association with ichthyosis linearis circumflexa. Br J Dermatol. 1969;81:851-7.
2. Chavanas S, Bodemer C, Rochat A, Hamel-Teillac D, Ali M, Irvine AD, et al. Mutations in SPINKS, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25: 141-2
3. Netherton syndrome. Journal of the American Academy of Dermatology. March 2010; Volume 62, Issue 3, AB71.
4. Abdalrheem, W., Alluhayyan, O., Alharbi, A. A Case Report on Netherton Syndrome. July 2020; 12(7): e9166.
5. Deng H, Xiao H. The role of the ATP2C1gene in Hailey-Hailey disease. Cell Mol Life Sci. 2017;74(20):3687-3696. doi: 10.1007/s00018-017-2544-7
6. Kieffer, J., Le Duff, F., Montaudie, H., Chiaverini, C., Lacour, J., Passeron, T. Treatment of Severe Hailey-Hailey Disease with Apremilast. JAMA Dermatology. December 2018; 154(12): 1453-1456.
7. Antonanzas, J., Tomas-Valazquez, A., Rodriguez-Garijo, N., Estenaga, A., Silido-Vallejo, R. Apremilast in Combination with Botulinum Toxin-A Injection for Recalcitrant Hailey-Hailey Disease. International Journal of Dermatology. October 2021; 61(5): 600-602.
8. Mansilla-Polo, M., Abril-Perez, C., Navarro-Mira, M., Botella-Estrada, R. Recalcitrant Hailey-Hailey Disease with Satisfactory Response to Apremilast. Actas Dermo-Sifiliograficas. June 2023.
9. Ang-Tiu, C., Nicolas, M. Ichthyosis bullosa of Siemans. Journal of Dermatological Case Reports. September 2012; 6(3)L 78-81.
10. Traupe, H., Kolde, G., Hamm, H., Happle, R. Icthyosis bullosa of Siemens: a unique type of epidermolytic hyperkeratosis. Journal of American Academy of Dermatology. June 1986; 14(6): 1000-1005.
11. Sanclemente, G., Falabella, R., Escobar, C. Ichthyosis Bullosa of Siemens: A Topical Therapy Option. JAMA Dermatology. February 1999; 135(2): 217-218.
12. Sticova, E., Kveton, M., Dubska, M., Kubatova, A. Acral peeling skin syndrome: An underdiagnosed skin disorder. Indian Journal of Dermatology, Venereology and Leprology. 2019; 85(3): 316-318.
13. Rivero, J., Dominguez, M., Blanco, P., Fernandez, R. Acral Peeling Skin Syndrome: A Case Report and Literature Review. ACTAS Dermo-Sifiliograficas. October 216; 107(8): 702-704.
14. Sarin, K., Sun, B., Bangs, C. Activating HRAS Mutation in Agminated Spitz Nevi Arising in a Nevus Spilus. JAMA Dermatology. September 2013; 149(9): 1077-1081.
15. Casso, E., Grin-Jorgensen, C., Grant-Kels, J. Spitz nevi. Journal of the American Academy of Dermatology. December 1992; 27(6): P901-913.
16. Gelbard, S., Tripp, J., Marghoob, A., Koenig, K., Kim, J., Bart, R. Management of Spitz nevi: A survey of dermatologists in the United States. Journal of the American Academy of Dermatology. August 2002; 47(2): P224-230.

September 2024 Case Study

Authors: Nidhi Shah, MD¹ and Karl Saardi, MD¹

1. Department of Dermatology, George Washington University School of Medicine and Health Sciences

Patient History

A 27-year-old male with no past medical history presented with a 1-year history of recurrent blisters throughout his body. Figure 1 demonstrates physical examination findings; there was no involvement of the oral or ocular mucosa. A punch biopsy for H&E was performed (Figure 2), and direct immunofluorescence (DIF) on salt-split skin demonstrated dermal staining.

Based on the clinical presentation and biopsy findings, what is the target for the circulating and tissue-bound autoantibodies?

A. LAD-1
B. Collagen VII
C. Laminin 332
D. BPAG2
E. Transglutaminase

Correct Answer: B

Explanation/Literature Review
Given the formation of tense bullae and vesicles in a young adult with biopsy findings demonstrating subepidermal cleavage with sparse inflammatory infiltrate and salt-split skin revealing staining on the dermal side, the patient was diagnosed with Epidermolysis Bullosa Acquisita (EBA), a very rare autoimmune blistering condition. The condition can be acquired at any age, with the median age of 50 years.¹ EBA is characterized by development of autoantibodies against collagen VII, which is a major component of anchoring fibrils in the hemidesmosomes found in the sub-lamina densa of the skin and mucous membranes.^1,2 On histology, there is subepidermal cleavage with or without inflammatory infiltrate based on the subtype of EBA. Further immunofluorescence studies demonstrate linear deposition of IgG and C3 at the basement membrane zone, with a u-serrated pattern and fluorescence only on the dermal side.^1,2 Salt split skin DIF is a challenging technique requiring an experienced immunodermatology lab, in which patient’s skin is preserved in IF media, treated with IM NaCl, and then processed for DIF. This technique can be especially helpful in diseases where IIF is negative, and ELISA assays are not available.³ Traditionally, immunoelectron microscopy is considered the “gold standard” for diagnosing EBA.

LAD-1 (choice A) and LABD97 are the targets for linear IgA bullous dermatosis (LABD) which generally affects elderly adults and preschool-aged children and has histopathology findings of IgA +/- C3 deposition along basement membrane with epidermal staining on salt-split skin.⁴ Laminin 332 (choice C) is the target for anti-epiligrin mucous membrane pemphigoid (MMP) which on salt-split skin also demonstrates dermal deposition of IgG, similar to EBA, however, the condition is classically seen in elderly patients and the lack of mucosal involvement makes the diagnosis less likely.^5,6 In bullous pemphigoid the targets include BPAG1 and BPAG2 (choice D), and clinically the presentation can be similar to the inflammatory subtype of EBA, however, on histology there would linear C3 and IgG deposition along the basement membrane in an “n-serrated” pattern with mostly epidermal staining on salt-split skin.⁷ Epidermal transglutaminase (choice E) is the target for dermatitis herpetiformis (DH), an autoimmune disease which always occurs in conjunction with celiac disease. IIF in DH is negative, and on DIF DH is differentiated from LABD by granular vs. linear IgA deposition at the basement membrane.⁸

Given the rarity of the condition and lack of randomized controlled trials, treatment is challenging and is based on case reports and findings from other autoimmune blistering conditions. First line options include systemic corticosteroids, IVIG, and immunomodulators including colchicine and dapsone, with immunosuppressants such as mycophenolate mofetil, azathioprine, and cyclosporine reserved as second line.^1,9 Often, EBA is resistant to these therapies and recent evidence supports the use of rituximab.^1,9

References

1. Kridin K, Kneiber D, Kowalski EH, Valdebran M, Amber KT. Epidermolysis bullosa acquisita: A comprehensive review. Autoimmun Rev. 2019;18(8):786-795. doi:10.1016/j.autrev.2019.06.007
2. Caux F. Diagnosis and Clinical Features of Epidermolysis Bullosa Acquisita. Dermatol Clin. 2011;29(3):485-491. doi:10.1016/j.det.2011.03.017
3. Bolognia J, Schaffer JV, Cerroni L, eds. Dermatology. Fifth edition. Elsevier; 2025.
4. Hull C, Zone J. Dermatology. In: Bolognia J SJCL, ed. Dermatology. Vol 31. e1 ed.; 2018:457-537.
5. Shi L, Li X, Qian H. Anti-Laminin 332-Type Mucous Membrane Pemphigoid. Biomolecules. 2022;12(10):1461. doi:10.3390/biom12101461
6. Carey B, Setterfield J. Mucous membrane pemphigoid and oral blistering diseases. Clin Exp Dermatol. 2019;44(7):732-739. doi:10.1111/ced.13996
7. Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol. 2019;94(2):133-146. doi:10.1590/abd1806-4841.20199007
8. Witte M, Zillikens D, Schmidt E. Diagnosis of Autoimmune Blistering Diseases. Front Med (Lausanne). 2018;5:296. Published 2018 Nov 2. doi:10.3389/fmed.2018.00296
9. Miyamoto D, Gordilho JO, Santi CG, Porro AM. Epidermolysis bullosa acquisita. An Bras Dermatol. 2022;97(4):409-423. doi:10.1016/j.abd.2021.09.010

February 2025 Case Study

Author: Olive Osuoji MD^1
1Department of Dermatology, The George Washington University School of Medicine and Health Sciences

Patient History
A 72-year-old male female with a past medical history of hypertension, end stage renal disease s/p renal transplant, type II diabetes mellitus, peripheral arterial disease, and atrial fibrillation was admitted to the hospital with right lower extremity (RLE) pain at rest and non-healing wounds. The patient had been admitted to the hospital 2 weeks prior for RLE angiogram with angioplasty. On examination, the patient had large well-defined necrotic ulcers with surrounding erythema on the right medial leg, right heel, and dorsal foot (Figure 1) and circumferential necrosis of the second through fifth right digits (Figure 2). Bilateral lower extremity dopplers showed triphasic signals. A punch biopsy was obtained from the periphery of the ulcer and H&E staining was performed (Figure 3). Laboratory findings were noncontributory.

Based on the clinical presentation and biopsy findings, which additional stain would be most useful to confirm the etiology of the underlying disease process?

A. Periodic acid-Schiff with diastase (PAS-D)
B. Colloidal iron
C. Von Kossa
D. Trichrome
E. Methenamine Silver

Correct Answer: B

Explanation/Literature Review
The patient presented clinically with retiform purpura and necrotic right lower extremity ulcerations two weeks following an angiogram with angioplasty. H&E stain of the punch biopsy specimen revealed amphophilic bilaminar material resembling hydrophilic polymer gel material within a dermal vessel, consistent with hydrophilic gel embolus. DIF revealed a non-diagnostic vascular fluorescence pattern, suggesting vascular damage without an immune complex-mediated vasculitis. These combined clinical and histopathological findings led to the diagnosis of cutaneous hydrophilic polymer emboli (HPE).

Cutaneous HPE is a rare iatrogenic occlusive vasculopathy that occurs after the use of polymer-coated intravascular devices. These devices – vascular catheters, delivery sheaths, coils, guidewires, grafts, and implants – are often coated with hydrophilic polymers to reduce friction between devices and vessel walls during endovascular procedures.^1-4 Despite its utility, the polymer gel coating can separate from the metallic surface of the device and embolize, causing vascular occlusion and ischemic damage. Fewer than 25 cases of HPE have been documented in the literature, but with the growing use of percutaneous endovascular procedures, recognition of HPE has increased.⁵

HPE can lodge in small dermal vessels, appearing clinically as erythema with pruritus, nonpalpable petechiae and purpura, livedo reticularis/racemosa, retiform purpura, acute and chronic ulcerations, hyperkeratotic and lichenified nodules, and hemorrhagic panniculitis. These lesions usually appear within 24 hours to 2 weeks of the procedure, though some cases may manifest months or even years later. Systemic complications of HPE can be severe and include pulmonary infarction, myocardial infarction, stroke, gangrene, and potentially death.^{1, 6}

When evaluating retiform purpura and necrotic ulcers on the lower extremities, etiologies of vascular compromise should be considered. The differential diagnosis includes calciphylaxis, vasculitides (small/medium vessel, ANCA-associated, drug-induced), cryoglobulinemia, and thrombotic/thromboembolic diseases such as cholesterol emboli, antiphospholipid syndrome, DIC, TTP, septic emboli, and medication-induced thrombosis (e.g., heparin-induced thrombocytopenia).^7-8

The gold standard diagnosis of HPE requires a combination of clinical findings and histopathological evidence of non-refractile, non-polarizable basophilic, amorphous material occluding mid-dermal vessels. Colloidal iron staining for acid mucopolysaccharides can be used to identify the polymer gel in HPE, but is not necessary. Colloidal iron staining can be combined with hyaluronidase digestion to differentiate between hyaluronic acid and other mucosubstances. An absence of tissue neutrophilia helps differentiate HPE from cholesterol emboli.^{1, 2, 6, 9}

Management of cutaneous HPE prioritizes early detection to avoid unnecessary amputation. Most cutaneous lesions of HPE spontaneously resolve without treatment as the polymer material biodegrades in vivo over weeks to months, however, supportive treatment for symptoms and secondary infections may be warranted. Evidence for the role of wound care, trials of topical or oral corticosteroids, surgical resection, and antiplatelet agents is only supported by case reports.^{1, 6, 8}

Incorrect Options ^10-12

• Periodic acid-Schiff (PAS) staining with diastase – glycogen, neutral mucopolysaccharide, and fungal stain; can be used to assist in identifying fungal organisms and inflammatory dermatoses
• Von Kossa – calcium stain; can be used to identify calciphylaxis
• Masson Trichrome – collagen stain; can be used to identify connective tissue abnormalities, perforating disorders, fibrosis, ischemic damage
• Methenamine Silver – fungal stain; can be used to identify angioinvasive fungal organisms

References

1. Chan KPR, Lee JSS, Lim JHL. Cutaneous Hydrophilic Polymer Embolism: An Important and Overlooked Clinical Entity. Am J Dermatopathol. 2024;46(7):452-454.
2. Miyaoka M, Hatanaka K, Uekusa T, Nakamura N. Clinicopathological features of hydrophilic polymer emboli in Japanese autopsy cases. APMIS. 2018;126(11):838-841.
3. Mehta RI, Mehta RI, Choi JM, Mukherjee A, Castellani RJ. Hydrophilic polymer embolism and associated vasculopathy of the lung: prevalence in a retrospective autopsy study. Hum Pathol. 2015;46(2):191-201.
4. Barnwell SL, D’Agostino AN, Shapiro SL, Nesbit GM, Kellogg JX. Foreign bodies in small arteries after use of an infusion microcatheter. AJNR Am J Neuroradiol. 1997;18(10):1886-1889.
5. Baudo M, Magrini E, Pernot M, et al. Hydrophilic polymer embolization after TAVI. J Cardiol. 2024;84(2):141-142.
6. Sabzevari N, Schapiro BL, Stewart B. Necrotic leg ulcers secondary to hydrophilic polymer gel emboli. J Vasc Surg Cases Innov Tech. 2019;5(3):310-313. Published 2019 Jun 29.
7. Georgesen C, Fox LP, Harp J. Retiform purpura: A diagnostic approach. J Am Acad Dermatol. 2020;82(4):783-796.
8. Shefler A, Blaszak SC, Shea CR, Chadha AA. A Rare Case of Hydrophilic Polymer Embolization After Transcatheter Aortic Valve Replacement. Am J Dermatopathol. 2023;45(6):411-413.
9. Thompson AK, Peters MS, El-Azhary RA, et al. Cutaneous microemboli from hydrophilic polymer after endovascular procedures. J Am Acad Dermatol. 2015;73(4):666-671.
10. Elston DM, Ferringer T, Ko C, Peckham S, High WA, DiCaudo DJ. Dermatopathology. Third edition. Elsevier; 2018.
11. Van De Vlekkert D, Machado E, d’Azzo A. Analysis of Generalized Fibrosis in Mouse Tissue Sections with Masson’s Trichrome Staining. Bio Protoc. 2020;10(10):e3629. Published 2020 May 20.
12. Shalin SC, Ferringer T, Cassarino DS. PAS and GMS utility in dermatopathology: Review of the current medical literature. J Cutan Pathol. 2020;47(11):1096-1102.