Renal Transplant Patient with a Black Toe

The patient is a 70 yo man who had a renal transplant around 10 years ago.  His immunosuppression consists of oral tacrolimus and prednisone, and he is seen annually by a dermatologist.  He had a 3 cm superficial squamous cell carcinoma ofhis scalp 5 years ago that was treated successfully with topical 5FU.

O/E: The current exam revealed a black area under the nail of the second toe on the left foot.  He said it's been like his for around a year and has not changed much.

Clinical and Dermatoscopic Images:

Diagnosis and Discussion:
While I am pretty certain that this is a subungual hematoma; if his history is accurate that may be worrisome.  There is little downside to removing the nail and biopsying the nail base if it is pigmented and this was scheduled in a week's time.  The fact that this is Morton's toe also favors subungual hematoma.

Subungual Pigmentation

The patient is a 49 yo woman who noted a discolored right great toe nail for ~ a week.  After a web search she became quite agitated and presented at the office as a walk-in patient.  The area was painless and there was no history of trauma.

O/E:  The patient is an anxious-appearing Korean woman. There was a dark purple area at the proximal and lateral portion of the right great toe nail.  Dermoscopically no brown or black color could be seen.  The nail was scraped down and the base appeared reddish.

Unfortunately the second photograph is a bit blurry.

Impression:  She short history and the pigment suggest subungual hematoma.  It would be unusual for a subungual melanoma to present this rapidly.

Plan:  I will follow this.  I expect it will take many months for this to grow out.

Dermatoscopic Dilemmas

The dermatoscope is a source of endless wonder.  Here are two cases seen in the past week.

1. Congenital Nevus of Special Site

This 5 month old bi-racial (Black/Caucasian) foster infant was noted to have a slowly enlarging pigmented lesion in his left crural fold since around one month of age.

photo taken by Dr. Yoon Cohen

Question/Comment: Would anyone do anything other than follow this child?  Is the gray veil significant? The symmetrically distributed brown clods are to my mind markers for a benign growing nevus (cobblestone pattern).  There is no pertinent literature about growth in small congenital nevi.  Melanoma, in this age group and ethnicity, is exceedingly rare.

2. Unusual Subungual Hematoma

A 72 yo woman noted nail pigmentation that appeared shortly after knee replacement surgery.  I do not know if she had been anticoagulated after surgery, but the information would help.  The subungual color under the cuticle may be an example of a "pseudo-Hutchinson sign."

1 month follow-up

Note:  The one month follow-up shows distal progression of pigmented area confirming the clinical impression of subungual hematoma.

Question/Comment: The fact that this appeared shortly after surgery strongly suggests trauma rather than neoplasia.  If the patient was anticoagulated during surgery, that would be one more helpful historical fact.  The pattern of the long band could be called the "tadpole sign" -- I wonder if it is specific for subungual hematoma.

References:
1. Precursors to melanoma and their mimics: nevi of special sites.

Elder DE. Precursors to melanoma and their mimics: nevi of special sites. Mod Pathol. 2006 Feb;19 Suppl 2:S4-20.  Free Full Text.

2. Dermnet.nz.org has good sections on dermtoscopy: Introduction to Dermatoscopy   Dermatoscopic Features 

3. Overview of Nail Dermatoscopy

Melanoma Does Not Read Textbooks I

Presented by Yoon Cohen, D.O. and David Elpern, M.D.

Abstract:  67-year-old man with a 3-month history of pigmented papules on the face and torso.

HPI: The patient is a 67-year-old man with a 3-month history of pigmented papules on the face and torso. He has past medical history of enucleation over 19 years ago for ocular melanoma. Since enucleation, he has been fairly healthy and staying active with his life. He has not noticed any recent weight loss, fatigue, and other associated constitutional symptoms.

O/E: The skin examination showed a pleasant and outgoing man with ~ 50 well defined 2-4 mm multiple scattered purple to blue-black firm papules on the face and torso. No lymphadenopathy noted. 

Clinical Pictures: 

Purple to blue-black firm papules on the cheek

Several scattered pigmented papules on the upper back

Dermoscopic View

Pathology: A dermal nodule of atypical, focally pigmented epithelioid cells exhibiting large nucleoli and focal tumor necrosis infiltrating the dermis and skeletal muscle consistent with metastatic malignant melanoma. No junctional component is present. Immunoperoxidase staining reveals the tumor cells to be positive for Mart-1/Melan-A, S100 and HMB45, confirming the histologic diagnosis.

Lab: CBC abd chemistries are normal. LDH is borderline high but not above normal range.

Imaging Studies: 

1. Abdominal Ultrasound: There are numerous heterogeneously hyperechoic masses within the liver, most compatible with metastatic disease. The largest of these is within the right hepatic lobe and measures up to 6.6 cm in greatest diameter. 

2. Chest PA/Lateral Xrays: No pulmonary nodules or pleural effusions are evident.

Diagnosis: Metastatic melanoma. Most likely ocular melanoma metastasis to the liver.

Discussion: 

This patient poses some therapeutic question.  His melanomas do not bother him at this point and he keeps saying that he feels fine.  He's an avid golfer.  If he gets plugged into the system and loses this season; can we promise him another season in 2014?  He is a simple man; retired, no outside source of income. His melanoma, dormant for 19 years is suddenly active again. Why?

Question:

Knowing chemotherapy may significantly affect his energy level and he may experience other significant side effects, we are not sure what would be the best option for this patient at this point. We'd appreciate you sharing your similar experiences with your patients.

Follow-up: Many attempts were made to contact the patient and get him back for a follow-up discussion; but he never answered his phone or returned letters.  He died ~ 5 months later.  We hope he payed a few rounds of golf over the summer and suspect that his life was easier without futile attempts at palliation.

References:
1. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture.
JAMA Ophthalmol. 2013 Apr;131(4):462-9. 

Grossniklaus HE.

Source

L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, GA 30322, USA. ophtheg@emory.edu

Abstract

IMPORTANCE:

To the best of my knowledge, this study demonstrates for the first time small, apparently dormant micrometastasis in the liver of patients with uveal melanoma.

OBJECTIVE:

To evaluate the histological and immunohistochemical findings in metastatic uveal melanoma to the liver.

DESIGN:

Samples of liver were obtained at autopsy from patients who died of metastatic uveal melanoma to the liver.

SETTING:

L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, Georgia.

PARTICIPANTS:

A total of 10 patients who died of metastatic uveal melanoma to the liver.

INTERVENTION:

Sections of the liver were examined with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, or reticulin stains.

MAIN OUTCOME MEASURES:

The tumors' morphology, growth pattern, mean vascular density, and mitotic index were determined with the aid of immunohistochemical stains for S100, HMB45, CD31, and Ki67.

RESULTS:

Stage 1 metastases (defined as tumor clusters ≤50 μm in diameter) were identified in the sinusoidal spaces of 9 of 10 patients (90%). Stage 1 metastases were avascular and lacked mitotic activity. Stage 2 metastases (defined as tumors measuring 51-500 μm in diameter) and stage 3 metastases (defined as tumors measuring >500 μm in diameter) were found in all patients. Immunohistochemical stains were positive for S100 or HMB45 in all tumors. Overall, stage 1 metastases outnumbered stage 2 metastases (which outnumbered stage 3 metastases). The mean vascular density and mitotic index increased from stage 2 to stage 3 metastases (P < .05). The architecture of stage 2 metastases mimicked the surrounding hepatic parenchyma, whereas stage 3 metastases exhibited either lobular or portal growth patterns.

CONCLUSIONS:

Uveal melanoma that spreads to the liver can be categorized as stage 1 (≤50 μm in diameter), stage 2 (51-500 μm in diameter), or stage 3 (>500 μm in diameter) metastases. The later stage exhibits a lobular or portal pattern of growth. During this progression, tumors become vascularized and mitotically active.

2. Domancy of Metastatic Melanoma

Pigment Cell Melanoma Res. 2010 Feb;23(1):41-56. 

Ossowski L, Aguirre-Ghiso JA.

Source

Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. liliana.ossowski@mssm.edu

Abstract

Metastatic dormancy of melanoma has not received sufficient attention, most likely because once detectable, metastasis is almost invariably fatal and, understandably, the focus has been on finding ways to prolong life of patients with overt recurrences. Nevertheless, analysis of the published clinical and experimental data on melanoma indicates that some aspect of melanoma biology imitate traits recently associated with dormancy in other solid cancers. Among them the ability of some melanomas to disseminate early during primary tumor progression and once disseminated, to remain undetected (dormant) for years. Comparison of cutaneous and uveal melanoma indicates that, in spite of being of the same origin, they differ profoundly in their clinical progression. Importantly for this discussion, between 40 and 50% of uveal melanoma remain undetected for longer than a decade, while less than 5% of cutaneous melanoma show this behavior. Both types of melanoma have activating oncogene mutations that provide autonomous pro-proliferative signals, yet the consensus is that those are not sufficient for tumor progression. If that is the case, it is possible to envision that signals from outside the tumor cell, (microenvironment) shape the fate of an individual disseminated cell, regardless of an oncogene mutation, to progress or to pause in a state of dormancy. To stimulate further debate and inquiry we describe here a few examples of potential signals that might modify the fate of disseminated cell and provide brief description of the current knowledge on dormancy in other cancers. Our hope is to convince the reader that disseminated melanoma cells do enter periods of prolonged dormancy and that finding ways to induce it, or to prolong it, might mean an extension of symptoms-free life for melanoma patients. Ultimately, understanding the biology of dormancy and the mechanisms of dormant cell survival, might allow for their specific targeting and elimination.

R/O Subungual Melanoma

70 yo man referred for suspected subungual melanoma.

HPI: The patient is a retired engineer with a one month history of subungual pigmentation. He suffers from Waldenstrom's macroglobulinemia and peripheral neuropathy. If he had injured his toe, he would not know.

O/E: The left middle toenail shows brown-blackish subungual pigmentation. It was difficult to appreciate if this was melanin or blood both clinically or dermoscopically. Hutshinson's sign is negative.


Dermoscopy before 3 mm punch biopsy

Diagnosis: Probably subungual hematoma. Need to r/o melanoma.

Procedure: Modification of Haneke Technique.

1. Patient soaks foot in warm water for 20 - 30 minutes
2. Carefully drive a 3 mm punch through the nail with care not to cut into the nail bed.
3. Lift off the cut disk of nail and observe the nail bed.


Dermoscopy after 3 mm punch biopsy and H2O2 to defect

In this case, what appeared to be dried blood was present. The area was cleaned with hydrogen peroxide and a normal appearing nail bed was see. There was no pigment noted. Dr. Hanecke's technique utilizes a Hemocult stick to test scraping from underside of nail, however, our strips were outdated and not reliable.

Note: Dr. Eckhart Haneke pioneered this technique but is not acknowledged in the literature. Here are his comments to this case: "Thank you very much for your email and the links, which I saw for the first time. Thank you also for giving me the credit.
You are completely right that we do not even need the hemoccult test strip for the correct diagnosis, but it is very convincing and impresses the patient. And of course, it is one more proof.
Also clinically, as this is no streaky lesion a melanoma is improbable - however, a very fast growing melanoma can appear like this.
When you apply hydrogen peroxide and the pigment disappears this is due to the hemodestructive action of H2O2 on erythrocytes: hemoglobin has a pseudocatalase action splitting H202 into H2O and O. That is why hydrogen peroxide is also a very good disinfective agent and I use it to cleanse my dermatosurgery field from blood."