Pathological evaluation of melanocytic lesionsHisashi Uhara
In this lecture, the following basic steps by which I routinely scan specimens in our hospital will be presented with examples.
1. Evaluate the specimen preparation.
1) Is the incision for the specimen made perpendicular to the skin surface?
2) Is the slice of tissue from volar skin made perpendicular to the furrows of skin?
2. Estimate the specimen size and location.
1) Estimate the size of the lesion from the magnification of the objective lens.
2) Estimate the specimen location.
3. Precaution before evaluation
1) Observe the specimens without clinical information as much as possible.
2) Obtain as much information as possible at low magnification.
4. The steps for observation
1) At low magnification: Check the symmetric properties and circumscription of the lesion based on the following points.
a. Distance from the densest area of the lesion to both ends.
b. Variation of the thickness of epidermis from the center to both ends.
c. Distribution of melanin in the coronoid layer, epidermis, and dermis.
d. Distribution of nests and distance between each nest.
e. Density of solitary distributed melanocytes.
f. Existence of inflammatory infiltration in the dermis and its distribution.
g. Continuity of the spread of nests and tumor cells in both ends.
h. Is the bottom of the lesion smooth or not?
2) At high magnification: Check the details of tumor cells.
a. Tumor cells in the epidermis: Existence of necrosis, atypia (large nucleolus), or mitosis.
b. Other findings in the epidermis: Distribution of melanin in the cornified layer, the existence of tumor cells in the upper epidermis, the polymorphism of tumor cells, the relationship between tumor cells and keratinocytes.
c. In the dermis: An overlapping, crowded, or sheet-like gathering of tumor cells, maturation of tumor cells, mitotic figures, or melanin of tumor cells at the bottom of the lesion.
d. In the adnexal area: The existence of tumor cells in adnexal walls.
5. After provisionally giving a pathological diagnosis, check discrepancies between the pathological diagnosis and clinical findings. Return to the pathological evaluation if necessary.
Pathological evaluation of melanocytic lesionsHisashi Uhara
In this lecture, the following basic steps by which I routinely scan specimens in our hospital will be presented with examples.
1. Evaluate the specimen preparation.
1) Is the incision for the specimen made perpendicular to the skin surface?
2) Is the slice of tissue from volar skin made perpendicular to the furrows of skin?
2. Estimate the specimen size and location.
1) Estimate the size of the lesion from the magnification of the objective lens.
2) Estimate the specimen location.
3. Precaution before evaluation
1) Observe the specimens without clinical information as much as possible.
2) Obtain as much information as possible at low magnification.
4. The steps for observation
1) At low magnification: Check the symmetric properties and circumscription of the lesion based on the following points.
a. Distance from the densest area of the lesion to both ends.
b. Variation of the thickness of epidermis from the center to both ends.
c. Distribution of melanin in the coronoid layer, epidermis, and dermis.
d. Distribution of nests and distance between each nest.
e. Density of solitary distributed melanocytes.
f. Existence of inflammatory infiltration in the dermis and its distribution.
g. Continuity of the spread of nests and tumor cells in both ends.
h. Is the bottom of the lesion smooth or not?
2) At high magnification: Check the details of tumor cells.
a. Tumor cells in the epidermis: Existence of necrosis, atypia (large nucleolus), or mitosis.
b. Other findings in the epidermis: Distribution of melanin in the cornified layer, the existence of tumor cells in the upper epidermis, the polymorphism of tumor cells, the relationship between tumor cells and keratinocytes.
c. In the dermis: An overlapping, crowded, or sheet-like gathering of tumor cells, maturation of tumor cells, mitotic figures, or melanin of tumor cells at the bottom of the lesion.
d. In the adnexal area: The existence of tumor cells in adnexal walls.
5. After provisionally giving a pathological diagnosis, check discrepancies between the pathological diagnosis and clinical findings. Return to the pathological evaluation if necessary.
Il recupero dei sapori perduti. - Ricette tipiche della tradizione Siciliana- Chiara Marescalco -Kiarma-
"IL RECUPERO DEI SAPORI PERDUTI" a cura del Prof. Alessandro Giglio.
Grafica e impaginazione a cura della Dott.ssa Chiara Marescalco.
Istituto Professionale “Paolo Calleri” IPSASR - IPSEOA - IPSSS PACHINO (SR) www.istitutomarzamemi.it
La storia del nostro territorio ha visto l’alternarsi di varie dominazioni straniere (greca, araba, normanna, angioina, aragonese) che lo hanno trasformato in un con- nubio di mondi diversi che si riflette in tutti gli aspetti della realtà e quindi anche nella gastronomia non esiste infatti
una cucina territoriale, ma varie tradizioni culinarie.
La cucina del territorio di Pachino mostra tracce di differenti culture che vi si sono stabilite negli ultimi due millenni e risente soprattutto dell’influenza dei Greci e degli Arabi.
Nei piatti si usava esclusivamente olio extravergine d’oliva, sia per cucinare che per condire mentre il burro era poco usato.
Gli ingredienti principali erano soprattutto vegetali o marini (pesce e molluschi).
La carne era utilizzata di rado e per lo più in forma di frattaglie.
Il pesce è stato tradizionalmente molto presente nel- le tavole dei pachinesi, servito fresco, aromatizzato con olio extravergine di oliva, con aglio, prezzemolo, con olive, capperi, pangrattato e arancia.
Il sale era soprattutto marino e i piatti erano
impreziositi dalle erbe aromatiche che crescono ancora oggi in abbondanza: basilico, prezzemo- lo, menta, alloro, origano, rosmarino, salvia, cipolle selva- tiche, semi di finocchio e finocchietto selvatico, insieme a gelsomino, pinoli, uva passa, pangrattato tostato (“muddica”), scorza d’arancia, succo di limone, inoltre cap- peri, aglio e cipolla sono spesso presenti nelle preparazioni.
Molto utilizzati anche erano mandorle e pistacchi, sia nel- la preparazione di dolci e di bevande che per condire riso e pasta.
Al centro dell’alimentazione c’era la pasta o un piatto
di legumi(fave fresche, fave secche, lenticchie, farro, ceci).
Molto consumato era il pane che accompagnava tutti i pasti.
Un capitolo a parte per i dolci (fritti, al forno, al cucchiaio) spesso a base di frutta fresca e secca consumati di solito per le tradizioni religiose.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Il recupero dei sapori perduti. - Ricette tipiche della tradizione Siciliana- Chiara Marescalco -Kiarma-
"IL RECUPERO DEI SAPORI PERDUTI" a cura del Prof. Alessandro Giglio.
Grafica e impaginazione a cura della Dott.ssa Chiara Marescalco.
Istituto Professionale “Paolo Calleri” IPSASR - IPSEOA - IPSSS PACHINO (SR) www.istitutomarzamemi.it
La storia del nostro territorio ha visto l’alternarsi di varie dominazioni straniere (greca, araba, normanna, angioina, aragonese) che lo hanno trasformato in un con- nubio di mondi diversi che si riflette in tutti gli aspetti della realtà e quindi anche nella gastronomia non esiste infatti
una cucina territoriale, ma varie tradizioni culinarie.
La cucina del territorio di Pachino mostra tracce di differenti culture che vi si sono stabilite negli ultimi due millenni e risente soprattutto dell’influenza dei Greci e degli Arabi.
Nei piatti si usava esclusivamente olio extravergine d’oliva, sia per cucinare che per condire mentre il burro era poco usato.
Gli ingredienti principali erano soprattutto vegetali o marini (pesce e molluschi).
La carne era utilizzata di rado e per lo più in forma di frattaglie.
Il pesce è stato tradizionalmente molto presente nel- le tavole dei pachinesi, servito fresco, aromatizzato con olio extravergine di oliva, con aglio, prezzemolo, con olive, capperi, pangrattato e arancia.
Il sale era soprattutto marino e i piatti erano
impreziositi dalle erbe aromatiche che crescono ancora oggi in abbondanza: basilico, prezzemo- lo, menta, alloro, origano, rosmarino, salvia, cipolle selva- tiche, semi di finocchio e finocchietto selvatico, insieme a gelsomino, pinoli, uva passa, pangrattato tostato (“muddica”), scorza d’arancia, succo di limone, inoltre cap- peri, aglio e cipolla sono spesso presenti nelle preparazioni.
Molto utilizzati anche erano mandorle e pistacchi, sia nel- la preparazione di dolci e di bevande che per condire riso e pasta.
Al centro dell’alimentazione c’era la pasta o un piatto
di legumi(fave fresche, fave secche, lenticchie, farro, ceci).
Molto consumato era il pane che accompagnava tutti i pasti.
Un capitolo a parte per i dolci (fritti, al forno, al cucchiaio) spesso a base di frutta fresca e secca consumati di solito per le tradizioni religiose.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Dr Patrick Treacy on Diagnosis and Treatment of Malignant Melanoma Dr. Patrick J. Treacy
A 23-year-old Siberian female patient presented with a changing lesion on her abdomen. The patient stated the lesion was present for about two years and it started
off from within a freckle, which started to grow larger and somewhat darken in appearance. It had the clinical appearance of a melanoma and the dermoscopy three-point checklist (designed to allow non-experts not to miss detection of melanomas) was used to determine whether this had a high likelihood of malignancy. It included:
Asymmetry: asymmetry of colour and structure in one or
two perpendicular axes
Atypical network: pigment network with irregular holes
and thick lines
Blue-white structures: there was some evidence of blue-
white veil and regression structures
Dr Patrick Treacy shares some of his most challenging cases.
This month he talks about treating Cutaneous Malignant Melanoma. Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes. They typically occur in the skin but may rarely occur in the mouth, intestines, or eye. In women they most commonly occur on the legs, while in men they are most common on the back. Sometimes they develop from a mole with concerning changes including an increase in size, irregular edges, change in color, itchiness, or skin breakdown
Dr Patrick Treacy treating Cutaneous Malignant Melanoma
Juten Et Al
1. Acta Chir Belg, 2010, 110, 475-478
A 71-Year-Old Woman with a Pigmented Nail Bed, which Persisted after Trauma
P. G. Juten*, **, J. W. Hinnen**
*St.-Antonius Hospital, Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Kleve, Germany ; **Medisch
Centrum Haaglanden, Department of Surgery, The Hague, The Netherlands.
Key words. Subungual melanoma ; melanoma ; melanoma in situ ; lentigo maligna ; nail bed pigmentation ; amputation.
Abstract. A 71-year-old woman presented in our out-patients department with pigmentation of the nail bed of her left
large toe, which had persisted after a trauma two years earlier. An inconclusive biopsy showed melanoma in situ. The
lesion was excised with amputation of the big toe at the IP-joint and closed primarily. The pathological diagnosis was
melanoma in situ and lentigo maligna. The lesion had been radically excised.
Case report
A 71-year-old woman was sent by the dermatologist to
our out-patients department with the suspicion of a sub-
ungual melanoma. She was sent for excision of this sub-
ungual melanoma which was located on her left big toe.
The lesion had been there for about two years. The
patient had noticed the lesion after a trauma to her toe.
At the moment of presentation she had no pain, only a
complaint about the easiness of bleeding of the lesion.
She had no medical history except for hypertension.
Physical examination showed a dark medial two-thirds
of the nail of the left big toe, with typical melanonychia
striata and destruction of the nail (Fig. 1). There were no
signs of ulceration or evidence of melanoma, such as the
Hutchinson’s sign (periungual extension of the pigmen-
tation). She had no palpable lymph nodes in her left
inguinal region.
Since subungual melanoma is a histological diagno-
sis, we first performed a diagnostic biopsy. This showed
melanoma in situ, but it was not conclusive. We decided
to amputate the first toe at the IP joint with the tip of
the first phalanx and close the wound primarily with
excision of some excess skin (Fig. 2). After the operation
the pathological diagnosis was lentigo maligna and
melanoma in situ which was radically excised.
Subungual melanoma is a rare diagnosis. Of all
melanomas it represents only 1-3% of cases (1). In Fig. 1
patients of Asian (2, 3) or African (4) origin this can be
as high as 20%. Boyer first described subungual
melanoma in 1854. It was Hutchinson in 1886 who onychomycosis, glomus tumour and pyogenic granulo-
called it “melanotic whitlow” because of its resemblance ma that are all benign. It is therefore often missed in the
to subungual infection (5). However, he emphasized its early stages. Subungual melanoma has a great preference
malignant character. Diagnosis of subungual melanoma for appearing at the first digits of both hands and feet.
is not easy because of the broad differential diagnosis, Fifteen percent of the subungual melanoma of the hand
which consists of subungual haematoma, paronychia, appears in the thumb and 53% of the lesions under the
2. 476 P. G. Juten et al.
a c
Fig. 2
often drawn to it because of an injury of some sort to the
affected nail. Usually, at this stage there are not yet any
symptoms. Later, symptoms of pain, discomfort, defor-
mity of the nail, ulceration, swelling and bleeding of the
nail and its surrounding tissues may occur.
About one fifth of the subungual melanomas seem to
be amelanotic, which makes diagnosis even more diffi-
cult. All pigmented lesions should be considered malig-
nant until proven otherwise. Therefore, in the literature,
early biopsy is proposed to prove the diagnosis histolog-
ically. If the first biopsy is not conclusive, efforts should
be made to obtain adequate material. The characteristic
lentiginous pattern of the melanoma is not always histo-
logically present or recognisable and it may also resem-
ble that of a nodular, superficially spreading or unclassi-
fiable variant of melanoma (9). As the level of thickness
differs from that of cutaneous melanoma with regard to
the prognosis, this is only a poor indicator and is very
b difficult to asses in subungual melanoma because of
the local micro-anatomy and desmoplasia (10, 11). In
the literature the prognostic factors that have shown to
be significant are : clinical stage at initial diagnosis,
nail of the big toe (6). The majority of patients with sub- ulceration of the tumour, bone invasion, proportion of
ungual melanomas are elderly, between the ages of 50 cells in the S-phase (6, 12).
and 70, with a mean age of about 55 years. Men and Because of the possible mutualising character of a
women are affected almost equally (7). Early diagnosis biopsy, some dermatologists prefer to perform a
of a subungual melanoma is relatively uncommon dermoscopy of the affected pigmented nail bed first. This
because of the broad differential diagnosis and the non-invasive method uses an immersion technique to
resemblance to infection. Most of the patients have been render the stratum corneum translucent (13, 14). With
treated for some kind of inflammatory disease and there- the provided magnification, dermoscopy can identify
fore the subungual melanoma is often unrecognised for 2 melanocytic lesions. The melanine is then found in
years or longer (8). Subungual melanoma usually begins cellular inclusions, which can be easily identified as
as dark brown/black colouration in the nail bed that fre- small granules less then 0.1 mm in diameter. Further
quently develops into bands or streaks (melanonychia evaluation of the colour and pattern of the pigmentation
striata) of pigmentation. The attention of the patient is could make dermoscopy a useful diagnostic tool. All
3. Subungual Melanoma 477
lesions with an irregular dermoscopy should be biopsied References
(15). The choice for a specific biopsy may also depend
1. FINLEY R. K., DRISCOLL D. L., BLUMENSON L. E. et al. Subungual
on the width of the longitudinal melanonychia (16-19). melanoma : an eighteen-year review. Surgery, 1994, 116 : 96-
For the best cosmetic outcome and the least destruction 100.
of the nail and nail bed the biopsy must be performed as 2. TAKEMATSU H., OBATA M., TOMITA Y. et al. Subungual melanoma : a
clinicopathological study of 16 Japanese cases. Cancer, 1985, 55 :
distally as possible (15). 2725-2731.
Earlier, in the times of Hutchinson, radical digital 3. DALY J. M., BERLIN R., URMACHER C. Subungual melanoma : a 25-
amputation was thought to be necessary and was the year review of cases. J Surg Oncol, 1987, 35 : 107-112.
4. PACK G. T., OROPEZA R. Subungual melanoma. Surg Gynecol
treatment of choice. This therapy causes handicaps in Obstet, 1967, 124 : 571-582.
both functional and cosmetic aspects. Nowadays, we see 5. HUTCHINSON J. Melanosis is often not black : melanotic whitlow.
in the literature that no difference is found in survival Br Med J, 1886, 1 : 491-496.
6. HEATON K. M., EL-NAGGAR A., ENSIGN L. G. et al. Surgical manage-
based on the level of amputation (20). Neither is there ment and prognostic factors in patients with subungual melanoma.
any difference found in the recurrence of the melanoma Ann Surg, 1994, 219 : 197-204.
if a digit is amputated proximally or distally (6, 12, 13, 7. BRIGGS J. C. Subungual malignant melanoma : a review article.
Br J Plast Surg, 1985, 38 : 174-176.
21). 8. PATTERSON R. H., HELWIG E. B. Subungual melanoma : a clinico-
Functional surgery in which the lesion is only locally pathologic study. Cancer, 1980, 46 : 2074-2088.
excised, versus partial amputation shows no difference 9. MCGOVERN V. J. Melanoma : histological diagnosis and prognosis.
1983 New York : Raven Press.
in recurrence either (22, 23). Excision with the Moh’s 10. KREMENTZ E. T., REED R. J., COLEMAN W. T. et al. Acral lentiginous
surgery technique has not been proved to be very melanoma : a clinicopathologic entity. Ann Surg, 1982, 195 : 632-
effective in the treatment of subungual melanoma yet, 645.
11. Paladugu R. R., Winberg C. D., Yonemoto R. H. Acral lentiginous
but it shows effectiveness in the excision of subungual melanoma. A clinicopathologic study of 36 patients. Cancer, 1983,
squamous cell carcinoma (24). Even local excision with 52 : 161-168.
a 1 cm margin, including excision of the periosteum of 12. O’LEARY J. A., BEREND K. R., JOHNSON J. L. et al. Subungual
melanoma : a review of 93 cases with identification of prognostic
the distal phalanx of the thumb in selected cases of variables. Clin Orthop, 2000, 378 : 206-212.
subungual melanoma with direct reconstruction with a 13. BRAUN R. P., RABINOVITZ H. S., OLIVIERO M. et al. Dermoscopy
local flap, shows promising results (25). of pigmented skin lesions. J Am Acad Dermatol, 2005, 52 : 109-
121.
There exists no consensus regarding sentinel node 14. MARGHOOB A. A., BRAUN R. P., KOPF A. W. Atlas of dermoscopy.
dissection. It has been suggested that all patients with New York : Taylor Francis, 2005.
subungual melanoma should have early lymph node 15. BRAUN R. P., BARAN R., LE GAL F. A. et al. Diagnosis and manage-
ment of nail pigmentations. J Am Acad Dermatol, 2007, 56 : 835-
dissection. However, no survival advantages are 847.
shown (26). In patients with locally advanced stages of 16. BARAN R., DAWBER R. P. R., DE BERKER D. A. R. et al. Diseases of
melanoma, isolated limp perfusion and infusion the nail and their management. 3rd ed. Oxford : Blackwell Science,
2001.
chemotherapy have proven to be effective (27-29). 17. BARAN R., PERRIN C., BRAUN R. P. et al. The melanocyte systems of
Because of the less invasive character and fewer compli- the nails and their disorders. In : NORDLUND J. J., BOISSY R. E.,
cations the isolated limp infusion technique tends to be HEARING R. et al. The pigmentary system. 2nd ed. New York :
Oxford University Press, 2005.
preferred as adjuvant therapy in metastatic melanoma 18. BARAN R., HANEKE E. Diagnose und Behandlung von longitudina-
disease. len Nagel Pigmentierungen. Hautarzt, 1984, 35 : 359-365.
Eight percent of all melanoma patients develop a 19. BARAN R., KECHIJIAN P. Longitudinal melanonychia (melanonychia
striata) : diagnosis and management. J Am Acad Dermatol, 1989,
secondary melanoma within 2 years of their initial 21 : 1165-1175.
diagnosis (30). Melanoma patients are at increased risk 20. PARK K. G. M., BLESSING K., KERNOHAN N. M. Surgical aspects of
of other skin tumours. In patients with lentigo maligna subungual malignant melanoma. Ann Surg, 1992, 216 : 692-695.
21. QUINN M. J., THOMPSON J. E., CROTTY K. et al. Subungual
melanomas, 35 percent develop another cutaneous melanoma of the hand. J Hand Surg Am, 1996, 21 : 506-511.
malignancy within 5 years (31). Currently, there is no 22. MOERHLE M., METZGER S., SCHIPPERT W. et al. “Functional” surgery
consensus about the frequency of follow-up. A time in subungual melanoma. Dermatol Surg, 2003, 29 : 366-374.
23. SLINGLUFF C. L. J., VOLLMER R., SEIGLER H. F. Acral melanoma : a
interval of 3-6 months in the first 3 years after initial review of 185 patients with identification of prognostic variables.
diagnosis and 6-12 months in the period thereafter is J Surg Oncol, 1990, 45 : 91-98.
accepted (32). 24. DE BERKER D. A. R., DAHL M. C. G., MALCOLM A. J. et al.
Micrographic surgery for subungual squamous cell carcinoma. Br
In conclusion, subungual melanoma is a rare diagno- J Plast Surg, 1996, 49 : 414-419.
sis, which is often delayed because of the broad differen- 25. RAYATT S. S., DANCEY A. L., DAVISON P. M. Thumb subungual
tial diagnosis and the resemblance to infection. Radical melanoma : is amputation necessary ? J Plast Reconstr Aesthet
Surg, 2007, 60 : 635-638.
digital amputation is not necessary, but partial amputa- 26. GIMOTTY P. A., YOON F., HAMMOND R., ROSENBAUM P., GUERRY D.
tion is recommended. Furthermore, local excision of the The therapeutic effect of sentinel lymph node biopsy in melanoma
lesion seems as effective as partial amputation. At this remains an open question. J Clin Oncol, 2009, 27 : 4236-4238.
27. THOMPSON J. F., HUNT J. A., SHANNON K. F. et al. Frequency and
moment, there is not a standard place for sentinel node duration of remission after isolated limb perfusion for melanoma.
dissection in the treatment of subungual melanoma. Arch Surg, 1997, 132 : 903-907.
4. 478 P. G. Juten et al.
28. NOORDA E. M., VROUENRAETS B. C., NIEWEG O. E. et al. Isolated 32. DUMMER R., HAUSCHILD A., PENTHEROUDAKIS G. Cutaneous malig-
limb perfusion : What is the evidence for its use ? Ann Surg Oncol, nant melanoma : ESMO clinical recommendations for diagnosis,
2004, 11 : 837-845. treatment and follow-up. Ann Oncol, 2009, 20 : 129-131.
29. KROON H. M., MONCRIEFF M., KAM P. C. et al. Outcomes following
isolated limb infusion for melanoma. A 14-year experience. Ann P. G. Juten, M.D.
Surg Oncol, 2008, 15 : 3003-3013.
St.-Antonius Hospital Kleve
30. TITUS-ERNSTOFF L., PERRY A. E., SPENCER S. K. et al. Multiple
primary melanoma : two-year results from a population-based Klinik für Unfall-, Hand- und Wiederherstellungschirurgie
study. Arch Dermatol, 2006, 142 : 433-438. Albersallee 5-7
31. AUSTRALIAN CANCER NETWORK. Guidelines for the management of 47533 Kleve, Deutschland
cutaneous melanoma. Sydney : Stone Press, 1997. E-mail : philip@juten.nl