Median Nail Dystrophy

Patient 1: A 65 yo woman with a 3 month history of a medial split in the right thumb nail. It is asymptomatic. No history of trauma. The physical exam showed the split begins at the proximal nail fold. There is a suggestion of erythema at its proximal end.

Patient 2: A 79 yo woman with a 3-6 months history of a medial split in the right thumb nail. It is painful with pressure otherwise asymptomatic. No history of trauma. The physical exam reveals the same finding as the patient 1 without a suggestion of erythema at the proximal fold. 

Clinical Images:  

Patient 1: Clinical View

Patient 1: Dermoscopic View

Patient 2: Clinical View

Patient 2: Dermoscopic View

Diagnosis: Median nail dystrophy.  Is this secondary to a subungual tumor? Is a biopsy indicated?

Reference:

Glomus tumor-induced longitudinal splitting of nail mimicking median canaliform dystrophy. Verma SB. Indian J Dermatol Venereol Leprol. 2008 May-Jun;74(3):257-9.

Abstract:Median canaliform deformity of the nail is an uncommon entity, where there is longitudinal splitting of the nail. Longitudinal splitting of the nail is a rare phenomenon and can also occur following number of growths arising in the nail matrix. On examination there was a longitudinal split in the nail plate, beginning in the distal nail fold and extending proximally all the way to the proximal nail fold. There was a small, almost indiscernible, swelling in that area, which was exquisitely tender. The split part of the nail showed a little discoloration. There was no discharge, bleeding, or subungual mass visible. 'Love test' was positive in this case. After nail avulsion, a small 2 mm x 4 mm nodule was exposed and excised. Histopathological examination of the tumor showed a mantle of glomus cells surrounding the blood vessels.  Free Full Text.

Cervical Nodules in a Healthy 65 Year-old Woman

Abstract:  One month history of three nodules in the right posterior cervical area in a 65 year-old woman.

HPI:  The patient is an otherwise healthy, immunocompetent woman who has noted three slightly painful nodules that appeared in the right posterior nuchal area. She has a history of  scalp excoriations.  She has two cats, one of which sleeps with her.

O/E:  Initially, there were three firm nodules measuring 0.8 to 1.5 cm in diameter.  She has had superficial scalp erosions secondary to excoriation for about a year.

Clinical Photos (courtesy of Yoon Cohen, D.O.)

Scar is biopsy site

Lab:  CBC normal, Chemistries normal.  Chest Xray normal.  Cat Scratch serology drawn six weeks after onset:  Bartonella Henselae IgG 1:1280 and Bartonella Quintana IgG 1:640  (IgM negative for both. Negative is <1:320)

Pathology: (photomicrographs courtesy of Lynne Goldberg, M.D., Boston University Skin Path) Because this was thought to be lymphadenopathy, a deep incisional biopsy was performed.  To our surprise, no lymphatic tissue was seen.  Rather, the pathology showed stellate subcutaneous microabscesses with a surrounding lymphohistiocytic infiltrate and fibrosis.

Course:  The patient continues to feel well.  An abscess was drained and around 1 cc of viscous pus was withdrawn.  It has refilled.  Since the patient feels well, we have not prescribed antibiotics.

Diagnosis: Cutaneous abscesses in Cat Scratch Disease.

Discussion: There are no reports of cutaneous abscesses in patients with CSD.  It may be possible that the suppuration we noted occurred as a sequela to an infected lymph node.  A review of the medical literature was not helpful here.  Recommendations for antibiotic therapy of immunocompetent with no systemic signs or symptoms are equivocal and we have elected to observe our patient for the time being.  If we decide to recommendad treatment, it will probably be with erythromycin.

References:

1.  eMedicine.comhttp://emedicine.medscape.com/article/214100-overview:  Catscratch disease (CSD), also known as catscratch fever or subacute regional lymphadenitis, is a bacterial infection affecting lymph nodes that drain the sites of inoculation. Bartonella henselae, a gram-negative rod, is considered the principal etiologic agent. CSD is a common cause of chronic lymphadenopathy in children and adolescents.

Patients with CSD usually have a history of sustaining a scratch or bite from a cat (typically a kitten). The initial symptom is formation of a papule at the inoculation site, followed by solitary or regional lymphadenopathy within 1-2 weeks (see the images below). In most patients, the disease resolves spontaneously within 2-4 months.

2. Abscess-forming lymphadenopathy and osteomyelitis in children with Bartonella henselae infection.  Ridder-Schröter R, et. al. J Med Microbiol. 2008 Apr;57(Pt 4):519-24. doi: 10.1099/jmm.0.47438-0.

Abstract: Bartonella henselae is the agent of cat-scratch disease (CSD), a chronic lymphadenopathy among children and adolescents. A systemic infection is very rare and most of these cases are found in patients with immunodeficiency. Here, cases involving four children of 6-12 years of age are reported. In immunocompetent patients, infection affects skin and draining lymph nodes; however, prolonged fever of unknown origin as in the fourth patient indicated a systemic complication of CSD. Free full text.

Median Nail Dystrophy

The patient is a 65 yo woman with a 3 month history of a medial split in the right thumb nail.  It is asymptomatic.  No history of trauma.

O/E:  The split begins at the proximal nail fold.  There is a suggestion of erythema at its proximal end.

Clinical Images:  Courtesy of Yoon Cohen

Diagnosis: Median nail Dystrophy.  Is this secondary to a subungual tumor?

Reference:

Glomus tumor-induced longitudinal splitting of nail mimicking median canaliform dystrophy. Verma SB. Indian J Dermatol Venereol Leprol. 2008 May-Jun;74(3):257-9.

Abstract:Median canaliform deformity of the nail is an uncommon entity, where there is longitudinal splitting of the nail. Longitudinal splitting of the nail is a rare phenomenon and can also occur following number of growths arising in the nail matrix. On examination there was a longitudinal split in the nail plate, beginning in the distal nail fold and extending proximally all the way to the proximal nail fold. There was a small, almost indiscernible, swelling in that area, which was exquisitely tender. The split part of the nail showed a little discoloration. There was no discharge, bleeding, or subungual mass visible. 'Love test' was positive in this case. After nail avulsion, a small 2 mm x 4 mm nodule was exposed and excised. Histopathological examination of the tumor showed a mantle of glomus cells surrounding the blood vessels.  Free Full Text.

Birt-Hogg-Dube Syndrome

Presented by Yoon Cohen, D.O. 
Alta Dermatology 
Mesa, Arizona

This patient's case courtesy of Bradley Kurgis, D.O. in San Luis Obispo, CA

Abstract: 54 yo woman with multiple white firm papules on the face since her 30s. 

HPI: This is a 54 yo woman with multiple scattered 2-4 mm white firm papules on the face and upper neck. She has first noticed her facial lesions at her late 30s. Previously a biopsy was obtained on the right cheek which showed sebaceous hyperplasia. 

She is not a smoker; however, she had four episodes of spontaneous pneumothorax in the past at her early 20s. At that time, she was informed that she had multiple "blebs" in her right lower lobe which resulted in the right lower lobectomy. Recently she had a colonoscopy with multiple benign polyps, otherwise, the only other heath issue is hypertension. Her father and paternal grandmother had the same skin findings on the face and the neck.  Her paternal grandmother also had episodes of pneumothorax in her right lower lobe and died of renal failure. No actual renal or thyroid cancers history in the family. No GI related malignancy in the family. 

The patient will be back in 2 weeks for another biopsy. If it shows fibrofolliculoma or trichodiscoma, we will obtain her renal ultrasound, abd/pelvic CTs and chest Xray. 

Family medical history of the patient

O/E: There are multiple scattered 2-4 mm white firm shiny papules throughout the face, the ear lobes and the upper neck. There are multiple acrochordons in the axillary areas which can be common findings in any individuals in her age group. No gingival papules or palmoplantar keratoses noted that you commonly observe in Cowden syndrome.

Clinical Photos (with permission of the patient): 

Dermatoscopic view shows well-demarcated areas of pallor with central follicular opening

Close-up view of dermatoscopic view

 Jarrett R, Walker L, Side L, et al. Dermoscopic features of Birt-Hogg-Dube Syndrome. Arch Dermtol. 2009; 145 (10): 1208.

Patient's father with the same facial lesions, deceased 2 years prior

Pathology: The repeated biopsy will be obtained 

Presumptive Diagnosis: Most likely Birt-Hogg-Dube Syndrome, but we also consider Cowden synydrome

Discussion: 
Birt-Hogg-Dubé syndrome (BHDS) was originally described in 1977 as the grouping of 3 skin tumors-the fibrofolliculoma, trichodiscoma, and acrochordon-in family members with an autosomal dominant inheritance pattern. [1] The condition is caused by germline mutations in the FLCN gene, which encodes folliculin; the function of this protein is largely unknown.[3] The recent years it has become clear that these 3 lesions likely represent only 1 of these tumors, the fibrofolliculoma. More important, evidence now supports a definite susceptibility to malignant renal tumors and pulmonary disease in patients with BHDS. Clinical recognition of this entity is possible in spite of the fact that several syndromes exist that are characterized by the presence of multiple firm facial papules.[1] [5] Jarrett, et al reported dermatoscopic findings of BHDS which showed well-demarcated pallor with central follicular opening. [2] The notably similar dermatoscopic findings were found in this patient. The presence of multiple and typical benign hair follicle tumors highlights the role of the dermatologist in the diagnosis of this rare genodermatosis that is associated with an increased risk of renal cell cancer and pulmonary cysts, warranting personal and familial follow-up and counseling.[4]

The patient reported that she has seen many physicians including dermatologists for her facial lesions in the past. However, she was repeatedly told that they could not help due to the generalized nature of the lesions, and she was dismissed without any further work-ups. Her case demonstrates our orphan patient today. 

Questions: 
1. What are your thoughts? Any suggestions for diagnostic studies?
2. The patient's most concern at this time is her facial appearance. Any treatment suggestions would be greatly appreciated.  

References:
1. Vincent A, Chan E, James W. Birt-Hogg-Dube syndrome: A review of the literature and the differential diagnosis of firm facial papules. J Am Acad Dermatol. 2003;49:698-705.

2. Jarrett R, Walker L, Side L, et al. Dermoscopic features of Birt-Hogg-Dube Syndrome. Arch Dermtol. 2009; 145 (10): 1208.

3. Menko FH, van Steensel MA, Giraud S, et al. Birt-Hogg-Dube syndrome: diagnosis and management. Lancet Oncol. 2009;10(12):1199-206.

4. Lencastre A, et al. Birt-Hogg-Dube syndrome. An Bras Dermatol. 2013;88:203-5.

5. Warwick Gm et al. Renal cancer associated with recurrent spontaneous pneumothorax in Birt-Hogg-Dube syndrome: a case report and review of the literature. J Med Case Reports. 2010;4:106.

CARP

Abstract: 36 yo Ecuadorian man with asymptomatic truncal hyperpigmentation x 8 months

HPI: The patient was seen on 2 January, 2014 complaining of the gradual development of hyperpigmentation on chest, abdomen and neck.  Good general health. He takes no medications by mouth.

O/E: confluent uniformly tan papules and plaques chest, abdomen, axillae and neck.  The primary lesions are barely elevated confluent papules and plaques. KOH negative.

Clinical Photos:

One Month Follow-up (Minocycline 100 mg b.i.d.)

 Pathology:
Hyperkeratosis and papilloimatosis  c/w CARP
Photos courtesy of Lynne Goldberg, Dermatologist.  Boston University School of Medicine.  Department of Dermatology and Dermatopathology

Diagnosis:  Confluent and Reticulated Papillomatosis of Gougerot and Cartaud (CARP)

Course:  The patient was placed on minocycline 100 mg b.i.d. and will be seen in followup in one month.  At one month, his CARP has resolved completely,

Discussion: CARP is a true "dermatologic vignette."  Once it is seen a few times, the diagnosis is clear.  Etiology is still a question, but the disorders remarkable improvement with minocycline should give us some clues.  Azithromycin appears equally as effective.  It also costs less than minocycline and has a more benign side-effect profile.

Reference:
1. eMedicine CARP

2.   Confluent and reticulated papillomatosis : a review of the literature.

Scheinfeld N.  Am J Clin Dermatol. 2006;7(5):305-13.

Abstract

Confluent and reticulated papillomatosis (CARP) was first described >60 years ago. It is distinct from acanthosis nigricans. This article presents the results of a review of the literature in MEDLINE through May 2006 using the terms 'confluent and reticulated papillomatosis', 'reticulated and confluent papillomatosis of Gougerot and Carteaud', and 'reticulated papillomatosis'. A recent report has linked the presence of Dietzia spp. (family: Dietziaceae; suborder: Corynebacterineae; order: Actinomycetales) in the skin to CARP. CARP has also been linked to defects in keratinization. CARP has been reported worldwide and occurs in both sexes, all age groups, and all races. The disorder can initially manifest as hyperkeratotic or verrucous papules that coalesce to form a reticular pattern peripherally and confluent plaques centrally. Although a variety of treatments for CARP exist, oral minocycline 50-100mg twice daily has been the preferred treatment. However, recent reports of the effectiveness of azithromycin 250-500mg three times weekly may make azithromycin the preferred treatment for CARP, since it has a more benign adverse effect profile than minocycline. Other effective antibacterial treatments include fusidic acid 1000mg daily, clarithromycin 500mg daily, erythromycin 1000mg daily, tetracycline 500mg twice daily, and cefdinir 300mg twice daily. If a recent finding that CARP is caused by a bacterial microorganism is replicated, treatment should likely be determined by bacterial sensitivities, antibacterial adverse effect profiles, and cost considerations. Other oral treatments of CARP that are effective but currently disfavored because of the effectiveness of minocycline include isotretinoin, acitretin, and etretinate. There have been mixed reports regarding the effectiveness of topical treatments, which include selenium sulfide, ketoconazole cream, tretinoin, tazarotene, tacalcitol, and calcipotriene (calcipotriol).

Prurigo Nodularis with Squamous Cell Carcinioma

Abstract: 63 yo man with 10 month history of intense pruritus and excoriated papules and nodules

HPI:   This 63 yo retired radio announcer presents with a 10 month history of intense pruritus and excoriated papules and nodules. He is in reasonable health.  Medications include Welbutrin (bupropion) and occasional prednisone for his itching.  He's tried topical steroids and anti-histamines without relief.  Smokes ~ 5 cigarettes a day.

O/E: Skin thin from actinic damage.  There are excoriated papules and nodules on the torso and extremities.  There are two or three more exophytic lesions.

Clinical Photos:

Lab:  CBC, chemistries normal.  IgE 867 IU/Ml

Pathology:  Initial bx signed out as SCC.  Since he has scores of lesions repeat biopsies of an early and more developed lesion were taken.  Thanks to Dr. Lynne Goldberg (Boston University Skin Path) for the beautiful photomics.
Prurigo Nodularis

Well_differentiated Squamous Cell Carcinoma

Diagnosis: Prurigo Nodularis with Squamous Cell Carcinoma

Discussion and Questions:The association of SCC with Prurigo Nodularis has only been reported one time (ref 5).  Yet we do not feel this is a chance association.  There are also some articles about P.n. and KA in the literature.
Has anyone seen a similar case?  He will be treated with gabapentin and followed. A follow-up will be posted in a month or so.  The SCCs will not be re:excised at this time.
Thaldomide has been recommended for P.N. in the literature, however, it is now > $10,000 per month!

References:

1. Journal of the American Academy of Dermatology

Volume 69, Issue 3, Pages 426-430, September 2013

Keratoacanthomas arising in association with prurigo nodules in pruritic, actinically damaged skin

Timothy P. Wu, BA, Kristen Miller, MD, David E. Cohen, MD, Jennifer A. Stein, MD, PhD  jennifer.Stein@nyumc.org

2. J Clin Pharm Ther. 2013 Feb;38(1):16-8. doi: 10.1111/jcpt.12005. Epub 2012 Sep 26.

Treatment of prurigo nodularis with pregabalin.

Mazza M, Guerriero G, Marano G, Janiri L, Bria P, Mazza S.

3. Dermatol Ther. 2010 Mar-Apr;23(2):194-8. doi: 10.1111/j.1529-8019.2010.01314.x.

Therapeutic hotline: Treatment of prurigo nodularis and lichen simplex chronicus with gabapentin.

Gencoglan G, Inanir I, Gunduz K.  (no real data on patient background)

4. Eur J Dermatol. 2008 Jan-Feb;18(1):85-6. Epub 2007 Dec 18.

Gabapentin for the treatment of recalcitrant chronic prurigo nodularis.

Dereli T, Karaca N, Inanir I, Oztürk G.  Available Free Full Text.

5.  Saudi Med J. 2000 Mar;21(3):300-1.

Squamous cell carcinoma complicating prurigo nodularis.

Al-Waiz MM, Maluki AH.

Abstract:  Squamous cell carcinoma complicating ulcerative prurigo nodularis is described in 2 patients who were having prurigo nodularis on dorsum of the feet for duration of many years. Biopsy specimens from the ulcerating nodules showed features of squamous cell carcinoma. This finding has not been previously reported. Squamous cell carcinoma should be considered in the evaluation of long standing ulcerative lesion of prurigo nodularis especially when not responding to conventional therapy.

Changing Nevus

Presented by:
Dr. Salvatore Donatello
Dermatologica e Venereologia. Catania, Sicilia


Abstract:  44 year old man with changing naevus

HPI:  The patient was seen in July of 2012 for a general cutaneous exam. He has Type IV skin. A naevus was noted on his right shoulder.  Dermatoscopic exam was felt to be not particularly worrisome but he was asked to return to have the lesion rechecked in six months.  He returned 18 months later.  The patient thought it had been present for many years and had not noted change.

O/E: July 2012:  5 mm in diameter dark brown papule  on right shoulder.  At the time, I thought the dermatoscopic exam looked normal.  It did look like an active lesions

January 2014:  The lesion is still 5 mm in diameter.  However, the brown clods noted on dermatoscopy in 2012 have disappeared and the lesion now looks uniformly dark gray.

Clinical photos:

Clinical Photo 31.1.14

Dermatoscopic Photo 31.1.14

Plan:  The lesion was excised with 3 mm margins on 31.1.14

Follow-up:  The biopsy report showed that this is an intradermal melanocytic without any atypical features. The brown clods in the first biopsy most likely are a sign of an active growing lesion.

Discussion:  Neither lesion on its own was very worrisome.  However, fortunately we have dermatoscopic images from July 2012 and January 2014.  The brown clods have disappeared and the lesion looks uniformly gray. Although the patient was asked to return in six months he did not do so.  We have no way of knowing if the change would have been noted then.
The pathology will tell us the story.  Is this an evolving naevus or a melanoma.  The practice of medicine can be humbling. There are few articles on evolving naevi in the literature.  This case will teach us something.

We will add an update after the biopsy is signed out. I have sent the specimen to a dermatologist in Napoli with a special interest in pigmented lesions.

Periodic Shedding of the Nails

Abstract:  2 year old girl with seven month history of nail shedding

HPI:  This otherwise healthy 2 year-old girl has been losing nails since about 18 months of age.  By history, the nails turn black and then are shed.  The patient's father says his small toe nail sheds periodicaly and his father may have a nail dystrophy, also.  This grandfather has a muscular disorder.

OE:  There are six or seven nails with which shoe subungual hemorrhage, onycholysis, nail dystrophy or absent nails.  Fingers are more affected than toenails, however, many of the toenails are dystrophic.

Clinical Photos:

12/10/13

1/14/14

Here is a two week f/u of nail direcctly about this photo.  It's amazing how quickly the nails of young children grow.

Diagnosis:

The clinical picture is consistent with what has been called Periodic Shedding of the Nails (PPS).  There are only two articles on this entity and both are difficult to obtain.  It is possible that what was called PPS is really a localized variant of Epidermolysis Simplex. Since this is such a young child, the true nature of the disorder may become evident with the passage of time.

Discussion: We will try to obtain some opinions from experts who may have some experience here.  It is likely that this is autosomal dominant with varying degrees of penetrence.  It may improve with age.  Trauma probably plays a role in damaging the nail bed, so one wonders if there is some defect of the nail matrix or bed.  The finger pad erosion pictured above may indicate that the problem is more wide-spread than the nail matrix.

References

1. Cutis. 1980 Jun;25(6):622-3.

Familial dystrophic periodic shedding of the nails.

Martin S, Rudolph AH.

Abstract  A patient with an autosomal dominant nail dystrophy characterized by periodic, asymptomatic shedding of the nails followed by regrowth is described herein. This highly penetrant disorder is similar to two earlier cases found in the dermatologic literature.

2.  Br J Dermatol. 1973 May;88(5):497-8.

Periodic shedding of the nails.

Main RA.

3. Localized epidermolysis bullosa simplex (Weber-Cockayne type).

Villaseñor-Park J, English JC. J Pediatr Adolesc Gynecol. 2011 Dec;24(6):410-2.

 

Desmoplastic Melanoma

Abstract: 83 yo man with a mixed desmoplastic melanoma of the scalp

HPI: In August 2013, this 83 yo man was seen with an 8 mm diameter nodule on the left parietal scalp present for  4 – 5 months and growing rapidly.  He had a history of two thin melanomas excised from the left forhead and left temple from 2009 – 2011.  In reviewing the biopsy reports, it can not be determined if they were both the same lesion or two separate tumors.

O/E: 8 mm pink to red well-circumscribed nodule left parietal. The dermatoscopic image shows multiple polymorphous blood vessels with central crystalline structures and a pink hue (vascular blush ) in the background.  No palpably enlarged lymph nodes.

Clinical Photos:

Dermoscopic Image - Courtesy of Yoon Cohen

Pathology:  Desmoplastic melanoma > 7.35 mm thick.  Level 5.  The tumor was/was not purely desmoplastic but over 10% of the cells has a spindle and epitheloid component as well.

Lab and Xray:

All blood studies including LDH within normal range.

P.E.T. Scan no abnormal foindings

Surgical Treatment: Patient underwent a WLE with 2 cm margins on October 2, 2013.  The defect was closed with a fasciocutaneous flap. Sentinel lymphnode biopsy was not performed.

Diagnosis: Desmoplastic melanoma with mixed histology, greater than 7.25 mm thick  No evidence of distant spread.

The patient has been seen at two centers for discussion of further treatment.  Local radiotherapy was recommended at both, although two different protocols were discussed.  The patient is undecided if he wants radiotherapy at this time.

Discussion:  The literature indicates that local radiotherapy reduces the incidence of local recurrence, but it is unclear if it provides an overall survival benefit.  At least one study suggests that patients undergoing local radiotherapy have a lower survival (ref 1 below).  It does not mention if these patients had more advanced disease that those who did not receive radiotherapy.

Questions:  What would your recommendations to this patient be?  Would you favor local radiotherapy?  See Discussion above.

References:

1. Desmoplastic melanoma - the step-child in the melanoma family?

Wasif N, Gray RJ, Pockaj BA.
J Surg Oncol. 2011 Feb;103(2):158-62.

Abstract

BACKGROUND AND OBJECTIVES: Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma. Our goal was to study the surgical management of DM, identify prognostic factors, and impact of treatment options.

METHODS: Patients with DM (n = 1,735) were identified from the Surveillance, Epidemiology, and End Results database (1988-2006).

RESULTS: The median age of the study population was 69 years and overall survival (OS) at 5 years 65%. DM was more common in males (65%), most commonly found on the head and neck (51%), and had a mean thickness of 2.97 mm. Patients undergoing a wide local excision (WLE; ≥1 cm) had improved 5-year OS compared to a simple excision (<1 cm) or biopsy alone (67% vs. 60% vs. 45%, respectively, P < 0.001). Of 505 patients (29%) undergoing sentinel node biopsy (SLNB), only 14 (2.8%) were positive. Traditional prognostic factors such as Breslow thickness, nodal positivity, and ulceration did not predict survival. On multivariate analysis only adjuvant radiation therapy [HR 1.65 (95% CI 1.17-2.31)] and WLE correlated with survival [HR 0.47 (95% CI 0.32-0.69)].

CONCLUSIONS: Desmoplastic melanoma does not share traditional prognostic factors with the melanoma family. Surgical resection with wide margins is needed to optimize survival and routine SLNB may be unnecessary. Furthermore, patients who received adjuvant radiation were at increased risk of dying (HR 1.65) and had decreased OS at 5 years (66% no radiation vs. 50% for adjuvant radiation, P < 0.001). Importantly, none of the traditional prognostic factors for cutaneous melanoma, such as site, Breslow thickness, Clark level, ulceration, and nodal status, had any impact on survival on univariate or multivariate analysis.
 

2. Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal. Free Full Text

Miller DD, Emley A, Yang S, Richards JE, Lee JE, Deng A, Hoang MP, Mahalingam M.

Mod Pathol. 2012 Apr;25(4):505-15. Free Full Text

Abstract

Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d.=5.6) versus 28% (s.d.=12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P=NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P=NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P=NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.

3.Subclassification of desmoplastic melanoma: pure and mixed variants have significantly different capacities for lymph node metastasis.

George E, McClain SE, Slingluff CL, Polissar NL, Patterson JW.

J Cutan Pathol. 2009 Apr;36(4):425-32.

Abstract

BACKGROUND: There is disagreement about the behavior and optimal management of desmoplastic melanoma (DM), particularly regarding the incidence of lymph node (LN) involvement. Recently, investigators have noted the frequently heterogeneous histologic composition of DM and have found significant differences between pure desmoplastic melanoma (PDM) (>or=90% comprised of histologically typical DM) and mixed desmoplastic melanoma (MDM) [>or=10% DM and >10% conventional melanoma (CM)].

METHOD: We reviewed 87 cases of DM comparing the histologic and clinical features of PDM (n = 44) to MDM (n = 43).

RESULTS: At surgical staging, there were LN metastases in 5 of 23 (22%) MDM patients, whereas all 17 PDM patients had negative LN biopsies (0%) (p = 0.04). PDM was less often clinically pigmented (36% vs. 67%) and had a lower mean mitotic index (1.3 vs. 3.0).

CONCLUSIONS: There are differences between PDM and MDM, the most important of which is the incidence of LN involvement. Our findings support the clinical utility of classifying DM into pure and mixed subtypes because the negligible rate of nodal involvement in PDM does not support the routine performance of sentinel LN biopsy in this subgroup of melanoma patients. In contrast, the incidence of LN involvement in MDM is comparable to that of CM.

4.  Desmoplastic malignant melanoma: a systematic review.

Lens MB, Newton-Bishop JA, Boon AP. Br J Dermatol. 2005 Apr;152(4):673-8.

Abstract

Prompt definitive surgical excision is the treatment of choice for DM. Improved knowledge of the clinical behaviour and histological features of DM is important for more effective management of patients with DM.

5. Desmoplastic melanoma: a review.

Chen LL, Jaimes N, Barker CA, Busam KJ, Marghoob AA.

Abstract:  Desmoplastic melanoma (DM) is a variant of spindle cell melanoma typically found on chronically sun-damaged skin of older individuals. Early diagnosis can be challenging because it is often amelanotic and has a predominantly dermal component. DM can be difficult to diagnose not only clinically but also histologically, and can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors when viewed on prepared histopathology slides. Pathologists have observed that DMs can manifest significant variation with respect to the extent of intratumoral cellularity, fibrosis, and/or perineural invasion. Furthermore, some tumors present with a pure desmoplastic invasive component (>90%) while other tumors display mixed features of DM and nondesmoplastic melanoma. This has led to the separation of DM into 2 histologic subtypes, pure and mixed. With a focus on the distinction between pure and mixed DM, this review will detail what is currently known about the diagnostic features of DM, discuss risk and prognostic factors, and examine the current literature on disease progression and management.