—  SPECIALTY CONFERENCE  —

Dermatopathology
7:30 PM, Monday, March 24
Marriott Ballroom, Salon 1


Mechanisms in Dermatopathology:
The Genesis of Melanoma and the Acquisition of the Metastasizing Phenotype




Moderator:

A. Neil Crowson
Regional Medical Laboratory & The University of Oklahoma
Tulsa, Oklahoma


Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view

Cases submitted by:

A. Neil Crowson
Regional Medical Laboratory & The University of Oklahoma
Tulsa, Oklahoma

Case 1

Clinical Summary:

A 47 year old man presented to his dermatologist with a dark spot on his arm. Physical examination showed a 0.9 x 0.7 cm brown flat lesion on his right arm. A shave biopsy was performed. Light microscopy showed a nested and single cell population of melanocytes at the dermo-epidermal junction with migration to the mid-spinous layers. These cells were epithelioid in character, had nuclei larger than adjacent keratinocytes, manifested abundant quantities of irregularly-melanized pale cytoplasms, and nuclei with prominent solitary nucleoli. There were no dermal stromal alterations one associates with dysplastic nevi.


Case 1 - Figure A - Low magnification showing pagetoid and nested array of atypical epithelioid melanocytes. There is a peri-retal stromal fibrosing reaction with perivascular lymphocytes, melanophages and telangiectasia.

Case 1 - Figure B - Intermediate magnification shows the loosely cohesive, pagetoid and nested array of atypical melanocytic cells.

Case 1 - Figure C - High power shows atypical nuclei with slight indentation of contour, small, discrete nucleoli and open chromatin patterns. The degree of cytologic atypia is not one associated with criteria for fully transformed malignant degeneration.

Case 2

Clinical Summary:

A 17 year old girl presented to her dermatologist's office with a "mole" in her genital area. Physical examination showed a 0.8 x 0.6 cm tan-colored, slighted elevated lesion on her right mons pubis. A shave biopsy was performed. Light microscopy showed nests of melanocytes at the dermo-epidermal junction that manifested multinucleated giant cells with pale cytoplasms and variably-sized pigment granules. The melanocyte nuclei were similar in size to those of adjacent keratinocytes and showed discrete nucleoli. There was prominent homogeneous stromal collagen superficially. The junctional component extended past the lateral confines of a banal dermal melanocytic populace in a symmetrical fashion. There were no mitoses in the melanocytes.



Case 2 - Figure A - Low power shows an asymmetric junctional extension of melanocytes with foci of central confluent growth, bridging between rete ridges and aberrant disposition of junctional nests along the shoulders of rete ridges and in the inter-rete epidermal bridge. There is a nested dermal nevomelanocytic component.

Case 2 - Figure B - Higher power magnification shows multi-nucleated giant melanocytes along the dermoepidermal junction. There is no appreciable lymphocytic inflammation in the dermis. An eosinophilic stromal condensation is present around rete ridges.

Case 2 - Figure C - High power showing the multi-nucleated giant melanocyte. The individual melanocytic nuclei are not atypical. The cytoplasms, however, are irregularly melanized with prominent pigment granules. The stromal fibrosing pattern is not one of lamellar fibroplasia as one associates with a dysplastic nevus.




Cases submitted by:

Boris Bastian
UCSF Comprehensive Cancer Center
San Francisco, California

Case 3

Clinical Summary:

47 year old man with a pigmented lesion on his right sole. CGH shows multiple aberration including amplifications of chromosomes 11q13 and 22q13.


Case 3 - Figure A - Acral skin biopsy, low power, showing a confluent nodular growth of atypical cells in the dermis with pagetoid spread through the overlying epidermis to the cornified layer. There is an asymmetric shoulder showing a lentiginous melanocytic proliferation.

Case 3 - Figure B - There is a confluent growth of atypical melanocytes along the dermoepidermal junction with pronounced pagetoid single cell spread to the cornified layer.


Case 3 - Figure C - At the lesional shoulder, a lentiginous array of fully transformed neoplastic melanocytes is present in the basal and immediate superbasilar spinous layers. The cells are hyperchromatic, polygonal and contracted and manifest fully transformed malignant cytologic features.

Case 3 - Figure D - The vertical growth phase component is predominantly spindled in character. There are admixed squamous pearls which represent down growths of squamous epithelium as a pseudoepitheliomatous reaction to the neoplasm. Cells show mitotic activity and fully transformed malignant features.

Case 4

Clinical Summary:

5 year old girl with a lesion on the left flank that was removed and recurred one year later. CGH did not reveal any chromosomal aberrations.


Case 4 - Figure A - Low power examination shows a polypoid nodule with a symmetrical profile. There is an inverted apical growth of melanocytes along adnexal structures toward the base of the biopsy extending into the subcutaneous tissue.

Case 4 - Figure B - Along the dermoepidermal junction are large nests of melanocytes showing vertically oriented spindled shaped cells in fasicles with a "raining down" architecture.

Case 4 - Figure C - High power shows atypical spindled shaped melanocytes in dermal based nodules. Rare mitotic figures are apparent.

Case 5

Clinical Summary:

33 year old man with a lesion of the left ear that was removed and recurred after several years. CGH showed multiple chromosomal aberrations.


Case 5 - Figure A - A low power micrograph shows confluent nodules of cells irregularly dispersed in the dermis associated with a dense sclerosing reaction.

Case 5 - Figure B - The melanocytic nests within the dense stromal collagen table show hyperchromatic and irregular nuclear contours.

Case 5 - Figure C - A high power micrograph shows nuclear hyperchromasia, endonuclear cytoplasmic inclusions and fully transformed cytologic features of malignancy.

Case 6

Clinical Summary:

45 year old man with a pigmented lesion on his back. CGH showed multiple chromosomal aberrations, but no amplifications.



Case 6 - Figure A - A low power micrograph shows a dermoepidermal nevomelanocytic proliferation with an asymmetric architecture and a lateral junctional shoulder.

Case 6 - Figure B - (intermediate power): Along the junctional shoulder melanocytes show a pagetoid pattern of migration to the upper spinous layers consistent with a radial growth phase melanoma.


Case 6 - Figure C - There is a vertical growth phase nodule in the dermis which is surmounted by a radial growth phase component.

Case 6 - Figure D - (high power): The vertical growth phase component shows fully transformed malignant nuclear features with frequent and atypical mitoses.




Cases submitted by:

Dirk J. Ruiter
University Medical Center Nijmegen
Nijmegen, The Netherlands

Case 7

Clinical Summary:

A 44 year old man with a blue-grey skin tumor of the left shoulder, 1.1 cm.


Case 7 - Figure A - A low power micrograph shows a confluent deforming dermal nodule with attenuation of the overlying epidermis. The tumor extends deeply into the reticular dermis.

Case 7 - Figure B - Intermediate power shows an intra-epidermal neoplastic component. The vertical growth phase nodules are larger than the overlying junctional nests or the nests seen in the adjacent epidermis in the microscopic field.

Case 7 - Figure C - (high power): The vertical growth phase nodule shows fully transformed malignant features in melanocytes showing a confluent growth pattern with frequent and atypical mitotic figures.

Case 8

Clinical Summary:

A 32 year old woman with an irregular black, partly grey-white slightly elevated mole of the right upper arm, 1.8 cm.



Case 8 - Figure A - A low power micrograph shows a sheet of melanocytes in the right half of the field with a confluent proliferation of intra-epidermal and intradermal neoplastic melanocytes in the left half of the field.

Case 8 - Figure B - An intermediate power micrograph shows regression with a confluent population of lymphocytes admixed with a band of melanophages in the absence of demonstrable neoplastic cells.

Case 8 - Figure C - A high power micrograph shows the intra-epidermal radial growth phase component manifesting nested upward migration in concert with a vertical growth phase dermal component in the dermis.




Cases submitted by:

Raymond Barnhill
George Washington University Medical School
Washington, DC

Case 9

Clinical Summary:

838-01: 51 year-old female with central back lesion biopsied to rule out squamous cell carcinoma.


Case 9 - Figure A - (intermediate power micrograph): In this vertical growth phase melanoma, tumor cells extend around a blood vessel in an abluminal disposition scaffolding along the outside of the basement membrane zone of the blood vessel.

Case 9 - Figure B - Intermediate to high power micrograph of the vascular field from figure 1.

Case 10

Clinical Summary:

C02-954: 61 year-old male with a lesion on the right chest biopsied by shave technique.



Case 10 - Figure A - A low power micrograph shows the base of the vertical growth phase component of this deeply invasive melanoma. There is angiolymphatic plugging by cohesive groups of neoplastic melanocytes.

Case 10 - Figure B - This blood vessel structure is distended by malignant melanocytes which are admixed with red blood cells.

Case 10 - Figure C - An intermediate power micrograph shows multiple involved blood vessels.




Cases submitted by:

Martin C. Mihm, Jr
Harvard Medical School
Boston, Massachusetts

Case 11

Clinical Summary:

This 40 year old woman had a pigmented lesion present on the shoulder for 2 years that gradually increased in size. A sentinel lymph node biopsy was negative.


Case 11 - Figure A - Intermediate power micrograph shows numerous cytotoxic lymphocytes admixed with neoplastic vertical growth phase melanoma cells.

Case 11 - Figure B - This intermediate power micrograph shows sheets of loosely cohesive fully transformed malignant epithelioid melanocytes admixed with lymphocytes.


Case 11 - Figure C - A high power micrograph shows cytotoxic lymphoid cells in apposition to a neoplastic melanocyte showing degenerating cytosol.

Case 11 - Figure D - A CD8 preparation shows cytotoxic lymphoid cells infiltrating the vertical growth phase component.

Case 12

Clinical Summary:

This 34 year old woman with stage 4 melanoma showed a vigorous 30 cm diameter response to autologous melanoma cells transfected with GM-CSF.



Case 12 - Figure A - (low power): The lower power magnification mimics erythema nodosum by showing septal inflammation with extension into adjacent fat lobules.

Case 12 - Figure B - The vaccination site shows an intense perivascular lymphocytic and eosinophilic infiltrate with no neoplastic melanocytes identified.