83RD SCIENTIFIC MEETING
UNIVERSITY OF NIJMEGEN
(95-5643-2 and 65112)
70 year old male with a nodule on the forehead which developed over 2-3 months, ulcerated and bled. Clinical examination revealed a 2cm ulcerated nodule with a pearly border and was considered to be a basal cell carcinoma (?rule out malignant melanoma). Excision was performed.
DIAGNOSIS: MERKEL CELL CARCINOMA
Top of file (96-12782)
A 15 year old girl presented with a raised reddish firm swelling of the tip of the nose. The lesion was not ulcerated or painful. No systemic or other abnormalities were noted. Clinical diagnostic possibilities were naevus? Fibroma? Xanthoma? Granuloma faciale? Lupus pernio?or Lupus vulgaris?
Sections are from a large surgical excision performed after previous small biopsies.
DIAGNOSIS: PRIMARY ALVEOLAR RHABDOMYOSARCOMA (RMS) OF THE SKIN.
Histology:
Medium-sized cells with round, oval nuclei containing one or two nucleoli proliferate from the papillary dermis to the deep layers of the dermis. Solid as well as alveolar growth pattern with loss of cohesion of tumour cells can be observed. There is no tumour necrosis. Multinucleated cells are not prominent. No granulomas; no eosinophlls. Mitoses can easily be found. PAS: strongly positive in scattered cells.
Immunohistochemistry:
Electron microscopy:
EM could only be performed on paraffin-embedded tissue. Nevertheless, some tumour cells still showed disorderly arranged clusters of actin and myosin filaments with Z-band material but no sarcomeres. No other specific organelles could be detected. The EM findings are consistent with rhabdomyoblastic differentiation.
Discussion:
Appropriate treatment of this case was to some extent delayed because of misinterpretation of the clinical presentation and the histopathological findings. In fact, the suggested initial diagnosis on a very small biopsy was a naevoid lesion.
The features of this small round cell tumour raise a long list of differential diagnoses at this age and can offer considerable diagnostic challenges, especially in a (too) small biopsy. Appropriate immunohistochemistry in conjunction with EM is needed for proper evaluation of such lesions. Rhabdomyosarcoma is only one of them and accounts for 5 to 8 % of childhood malignancies of soft tissues. In addition, primary rhabdomyosarcoma of the skin is (extremely) rare. Schmidt et al (1) could collect only 5 cases among a total number of 682 rhabdomyosarcomas (0,7 %). Thirteen cases of 35 (37 %) primary malignant cutaneous tumours were classified as RMS by Ma de la Luz Orozco et al (7) in a large series of 36.207 pediatric dermatology patients. Almost all the cases presented in the skin of the face (nose, cheek, eyelid). The same is true for the other casuistical reported cases (2, 3, 4, 7). Metastatic cutaneous lesions from rhabdomyosarcoma are equally rare.
Most cutaneous cases belong to the alveolar subtype of RMS even at the very young age. This parallels the situation of RMS of the extremities.
Follow-up:
Adequate plastic surgical excision was performed which yielded negative cutting surfaces.
Chemotherapy was given according to the conventional schedule. The patient is still in good condition after 2.5 years.
References
Top of file (9398/92)
Female of 81. Tumour over scapula measuring 1.5cm in diameter. Duration 6 months.
DIAGNOSIS: METASTATIC CARCINOMA
Follow up in this case not known
Differential diagnosis: Eccrine ductal carcinoma.
Refs:
Top of file (MAC93/96)
Male of 43 years. Tumour on cheek for 4 years
DIAGNOSIS: MIXED TUMOUR
No follow up in this patient
References
with pleural effusion, sarcoma cells in aspirate. Patient died November 1990.
Differential Diagnosis.
Refs:
Top of file (200411)
14 year old female with lesion of retro-auricular area.
DIAGNOSIS: COMPOUND SPINDLE CELL NEVUS
Differential diagnosis
Spindle cell nevi represent a broad category of benign melanocytic lesions containing several distinctive clinico-pathologic entities, such as pigmented spindle cell nevus (Reed nevus), epithelioid and spindle cell nevus (Spitz nevus), blue nevus, deep penetrating nevus, or plexiform spindle cell nevus. However, some lesions are categorized only with difficulty and are best designated as spindle cell nevus.
It must be emphasized that spindle cell nevi can be easily overdiagnosed as melanoma.1 In a recent review of 130 lesions initially diagnosed as melanoma in children aged 16 or less, a vast majority of the lesions which were reclassified as nevus contained a predominance of spindle cells.2 On the other hand, melanomas associated or not with desmoplastic features can contain a majority of spindle melanocytes.
1) Pigmented spindle cell nevus (Reed)
The pigmented spindle cell nevus (PSCN) is important to recognize because of its frequent confusion with melanoma. It is typically a dark, symmetric, and sharply circumscribed lesion.3 PSCN is preferentially located on th extremities, especially the thigh, with a peak incidence in the third decade.4,5
Histologically, this lesion is small, strikingly well circumscribed, and remarkable for its presence of intraepidermal nests of spindle cells, some heavily pigmented, and often separated from the adjacent epidermis by prominent clefts. These nests are often vertically oriented and may vary in size and shape. Most of the PSCN are junctional or superficial; if dermal involvement occurs, the dermal component is usually confined to the papillary dermis. The spindle melanocytes are often uniform, containing a nucleus smaller than the nuclei of adjacent keratinocytes.6 Anisocaryosis is rare and, if present, needs to be viewed as an atypical feature. Some PSCN, particularly but not only in children, show prominent pagetoid spread simulating melanoma in situ.
The features always important to evaluate for the differential diagnosis with melanoma are the symmetry, sharp lateral borders, cytologic uniformity, regularity of nests, vertical orientation of spindle cells, coarse melanin. Maturation can be difficult to observe in these thin lesions.
2) Spindle and epithelioid cell nevus (Spitz)
One must recognize that the topic of melanocytic lesions in children is still mainly focused on the difficulties the pathologist encounters for the differential diagnosis between some melanomas and the so-called Spitz and related nevi. Fifty years after their description, Spitz nevi continues to lead to overdiagnoses of melanoma.
In 70 to 85% of the cases, Spitz nevi are diagnosed before 20 years of age.7,8 They may occur anywhere on the body with a predominance for the face and the lower extremities. Most commonly they present as a solitary red-pink, dome-shaped, nodule.
The most distinctive histologic features of Spitz nevus is the presence of large epithelioid and/or spindle melanocytes. Spindle cell melanocytes in Spitz nevi contain fusiform, plump, eosinophilic cytoplasm, with sharp borders. Nuclei can be large, but nuclear contours are typically smooth and regular. They contain often a single, well visible, amphophilic nucleolus. At the dermoepidermis junction, the spindle cells are arranged in fascicles or elongated nests, often vertically oriented. Their plump cytoplasm, their nuclear features, their arrangement in vertically oriented fascicles make spindle cell nevi often easily recognizable and distinct from spindle cells of other nevi. Other characteristic, but inconstant, features of Spitz nevi include overall monomorphous population of cells, symmetry, orderly arrangement of melanocytes in the dermis, melanocytes loosely arranged at deep margin, rarity of deep mitoses, perivascular inflammatory infiltrate, telangiectasia, edema, and superficial pigmentation. The presence of epidermal changes with acanthosis and hypergranulosis can be useful.9
However, cellular pleomorphism can be striking, with high mitotic activity, and lack of maturation. In rare circumstances unequivocal distinction between Spitz nevus and melanoma is practically impossible.
3) Blue nevus (spindle cell variant)
This type of blue nevus is characterized by a prominence of spindle cells relative to dendritic cells and fibrous tissue. These spindle melanocytes are isolated or arranged in fascicles in the dermis. They are associated with a variable numbers of dendritic melanocytes, melanophages, and fibrosis. Sometimes, these lesions display a plexiform architecture with cellular foci deeply located. Mitoses are rare. There is no lentiginous melanocytic proliferation at the dermoepidermis junction.
4) Deep penetrating nevus (DPN) and plexiform spindle cell nevus
DPN must be recognized because of its frequent confusion with melanoma.10 In the original report, DPN was described mostly on the face and upper trunk of patients ranged in age 10 to 30 years. Histologically, these lesions are striking by their symmetric, well-circumscribed configuration with involvement of the deep dermis or fat as an inverted wedge. Large pigmented spindle cells are packed in fascicles or nests. Junctional nests can be observed. Melanophages are often numerous. Cytologic atypia can be present. Mitoses are absent or rare.
Plexiform spindle cell nevus is closely related with PSCN, Spitz nevus, blue nevus, and DPN.11,12 It illustrates the overlap between the different sub-categories of spindle cell nevi. It occurs mostly on the shoulders and back of young adults (mean age 22 years). Histologically, plexiform spindle cell nevus resembles DPN but is more superficial and displays striking plexiform arrangement of pigmented spindle cells along adnexal structures and neurovascular bundles. As in DPN cytologic atypia can be present. Mitoses are absent or rare.
5) Childhood melanoma
It cannot be overemphasized that childhood melanoma are rare and extreme caution should be exercised when diagnosing melanoma in a child as some benign lesions exhibit similar histologic features.
Parameters always important to evaluate and arguing in favor of a nevus are symmetry, cytologic uniformity, regularity of junctional nests, maturation, and lack of deep mitoses. However, there is no single criterion by which a diagnosis of nevus or melanoma can be made and some spindle cell nevi can have marked cellular pleomorphism, with numerous mitoses.
Beside the childhood melanomas similar to these encountered in adults, childhood melanomas can be categorized in three main groups based on the predominant cellular population and the overall architectural appearance. These categories could have different differential diagnoses and carry specific prognoses.2,13
References
1. Smith NP. The pigmented spindle cell tumor of Reed: An underdiagnosed lesion. Semin Diagn Pathol 1987;4:75-87.
2. Spatz A, Ruiter D, Hardmeier T, et al. Melanoma in childhood: an EORTC-MCG multicenter study on the clinico-pathological aspects. Int J Cancer 1996;68:317-324.
3. Reed RJ, Ichinose H, Clark WH, Mihm MC Jr. Common and uncommon melanocytic nevi and borderline melanomas. Semin Oncol 1975;2:119-47.
4. Barnhill RL, Barnhill MA, Berwick M, Mimh MC Jr. The histologic spectrum of pigmented spindle cell nevus: A review of 120 cases with emphasis on atypical variants. Hum Pathol 1991;22:52-8.
5. Barnhill RL, Mimh MC Jr. The pigmented spindle cell naevus and its variants: Distinction from melanoma. Br J Dermatol 1989;121:717-26.
6. Sagebiel R, Chinn E, Egbert B. Pigmented spindle cell nevus: Clinical and histological review of 90 cases. Am J Surg Pathol 1984;8:645-53.
7. Paniago-Pereira C, Maize JC, Ackerman AB. Nevus of large spindle and/or epithelioid cells (Spitz's nevus). Arch Dermatol 1978;114:1811-23.
8. Weedon D, Little JH. Spindle and epitheloid cell nevi in children and adults. A review of 211 cases of the Spitz nevus. Cancer 1977;40:217-25.
9. McCarthy SW, Crotty KA, Palmer AA, Ng ABP, McCarthy WH, Shaw HM. Cutaneous malignant melanoma in teenagers. Histopathology 1994;24:453-461.
10. Seab JA Jr, Graham JH, Helwig EB. Deep penetrating nevus. A J Surg Pathol 1989;13:39-44.
11. Cooper PH. Deep penetrating (plexiform spindle cell) nevus: A frequent participant in combined nevus. J Cutan Pathol 1992;19:172-80.
12. Barnhill RL, Mimh MC Jr, Magro CM. Plexiform spindle cell nevus: A distinctive variant of plexiform melanocytic naevus. Histopathology 1991;18:243-7.
13. Barnhill RL, Flotte TJ, Fleischli M, Perez-Atayde A. Cutaneous melanoma and atypical spitz tumors in childhood. Cancer 1995;76:1833-45.
Top of file (transparencies distributed)
Female of 38 years with small nodule on back
DIAGNOSIS: DEEP PENTRATING NAEVUS COMBINED WITH COMMON ACQUIRED NAEVUS.
Slide:
Low power field of entire lesion, showing superficial portion with features of common acquired naevus, and a subjacent portion of larger, slightly pigmented cells, which centre around a sweat gland and deeply penetrate the dermis.
Diagnosis:
Deep penetrating naevus in combination with common acquired naevus. The superficial portion of the naevus exhibits the cytological and architectural features of a common acquired compound naevus. In the author's material, such lesions combining areas of deep penetrating naevus with areas with the features of common acquired naevus outnumber "pure" deep penetrating naevi. When confronted with such a lesion, an additional diagnostic problem is the fact that (as in combined "true and blue' naevi) there is a population of pigmented cells which is distinct from the surrounding/overlying component, which may result in an erroneous impression
of malignant transformation. Indicators of benignity are: absence of mitoses (a very small number of mitosis is, however, occasionally seen), absence of marked nuclear pleomorphism in conjunction with abundance of cytoplasm (areas of melanoma with monomorphic nuclei generally exhibit a paucity of cytoplasm), absence of intradermal inflammation and fibrosis (often, but by no means always, present, at least focally, in thick melanomas). The general impression of a quiet" population of slightly pigmented, cytoplasm-rich melanocytes adjacent or subjacent of a common acquired naevus is characteristic of this naevus variant.The deep portion of the naevus shares some features of blue naevus: deep dermal penetration, pigmentation (usually), absence of so-called maturation towards the base of the lesion, and, occasionally, the presence of mitotic figures. In addtion, as indicated above, the frequent presence of an overlying or adjacent common acquired naevus, is not at all uncommon in blue naevus, especially of the "cellular" variant, deep penetrating naevus and blue naevus may well be related entities.
References:
Top of file (9154D/97 transparencies distributed)
72 year old female; slide of the second biopsy of a facial lesion. The previous biopsy had been reported as a fibrous scar.
DIAGNOSIS: DESMOPLASTIC MELANOMA SIMULATING HYPERTROPHIC SCAR.
Previous history 1994 lesion on cheek diagnosed as lentigo. 1995 nodule in scar diagnosed as scarring reaction. 1996 further nodule diagnosed as hypertrophic scar. Original histology was of a benign lentiginous proliferation. Subsequent biopsies of "scar" were actin positive and S100 HMB45 negative.
1997 re-presented with invasive mass of clearly atypical spindle cell tumour which was S100 positive and actin patchily positive.
Desmoplastic melanoma has strong tendency to local recurrence; regional or distant mets. are late and uncommon. Has better survival compared to non desmolplastic melanoma of the same thickness. These trends are more marked when neurotropism is present
Reference
Top of file (12807L/95 transparencies distributed)
58 year old male; slide of pigmented lesion from the back
DIAGNOSIS: SUPERFICIAL MELANOMA WITH METASTATIC POTENTIAL
1990 flat pigmented lesion on back; 1990 melanoma in situ ?invasion 1994 regional lymph node mets; 1995 died of cerebral mets.
The lack of obvious invasion and thinness raises the problem of recognising the minimum features of metastatic potential.
Top of file T97-3368.
Male 68 years with a 3cm tumour of the left arm for 2 months. No extracutaneous manifestations noted.
DIAGNOSIS:PSEUDO B-CELL LYMPHOMA
A 68 year old male presented with a tumor with a diameter of 3 cm on the left fore arm existing for 2 months. No lymph node enlargements were found. Clinically the following diagnose was considered:
Cutaneous B-cell lymphoma, pseudo B-cell lymphoma or cutaneous T-cell lymphoma.Terms used in the past for pseudo B-cell lymphomas are:? Sarcomatoid of Spiegler-Fendt, lymphocytoma, lymphadenosis, benigna cutis and cutaneous lymphoid lymplasia.
The histology of the tumor showed diffuse and nodular lymphoid infiltrates with reactive secondary lymphoid follicles.
The infiltrate outside the follicles showed a mixed cellular infiltrate with blast cells intermingled with small lymphoid cells in a background of vessels often lined high endothelial cells (high endothelial vessels), suggesting B-cell lymphoma. In some slides a granuloma could be found. Immunohistochemistry showed that many blasts were CD20+, but several blasts cells were positive for CD3 and CD45RO..
>From the small lymphoid cells many stained for CD20 and a minority for CD3 and CD45RO.
Staining for K and L did not reveal light chain restriction. Staining for CD4 and CD8 showed a ratio 2:1 for the T-cells. Staining for CD21 revealed follicular dendritic cells only in the reactive follicles.
Thus in this infiltrate with a predominance of B-cells and a minority of T-cells both the T and B cell lineage were activated without evidence for clonality of the B-cell lineage. Therefore the diagnosis pseudo B-cell lymphoma was made. Pseudo B-cell lymphomas are characterized by features suggestive of B-cell lymphoma with sheets or clusters of B-cells and/or plasma cells and with variable numbers of reactive T-cells. The B-cells compartment is composed of polytypic B cells, as defined by immunohistochemical analysis. These lymphoid hyperplasias can be caused by Borelia Borgdorferi1, Herpes Zoster, antigen injection2, accupuncture3, or after performing a tattoo.
However, in many cases the cause of the disease is unknown as in this case.
In the past, the presence of follicular structures, and a top heavy infiltrate were considered by many authors to be specific for cutaneous pseudo B-cell lymphoma, but recent studies show that they are also frequently seen in primary cutaneous follicular center cell lymphomas, and immunocytoma (extra nodal marginal zone B-cell lymphoma). More specific are a mixed cellular infiltrate, the presence of nuclear dust and the presence of eosenophils.
However, the corner stone is i.e. the demonstration of absence of light chain restriction by immunohistochemistry.
Although clonal immunoglobulin gene rearrangements are often considered diagnostic for cutaneous B-cell lymphomas this technique has in our hands proven to be less sensitive since we found also clonal rearrangements in pseudo B-cell lymphomas, which has been defined histologically and clinically5.
References
Top of file T97-15859
Male 69 years with a 2cm tumour of the right cheek for 3 months. Identical lesion on the left upper leg was found on clinical examination. No lymph nodes palpable. No extracutaneous lesions. Biopsy from the cheek lesion.
DIAGNOSIS: LARGE B-CELL LYMPHOMA
Clinically a pseudo B-cell lymphoma, a cutaneous B-cell lymphoma, and a cutaneous T-cell lymphoma were considered.
No nuclear dust was observed in these blast rich areas. A diffuse monomorphic infiltrate of CD20+ blasts (mainly centroblasts) was observed. No reactive follicles were present. Histologically a band free zone of infiltrate under the epidermis was seen. Immunohistochemically the blasts cells stained positive for CD20 and CD79 but negative for T cell marker (CD3, CD45RO) and bcl-2. Between the blast cells a few reactive T-lymphocytes were seen. Surface immuno-globulin was absent. Based on these finding the diagnosis primary cutaneous follicle center cell lymphoma was made. Treatment consisted of radiation of the two lesions. Half year follow up showed complete healing without reaccurence.
Three types of primary cutaneous B-cell lymphomas can be differentiated1;
1) primary cutaneous follicle center cell lymphomas mainly occuring on the head and the trunk with a good prognosis.
2) primary cutaneous immunocytoma (extra nodal marginal zone B-cell lymphoma mainly presenting on the extremities with a good prognosis.
3) Large B-cell lymphoma of the leg with an intermediate prognosis.
Interestingly, in contrast to primary cutaneous follicle center cell lymphoma, large B-cell lymphoma of the leg is bcl-2+. The absence of bcl-2 expression in a primary cutaneous follicle center cell lymphoma localized on the head and the trunk can be used to differentiate this lymphoma from a secondary skin localisation of a node based follicle center cell lymphoma.
Although most authors accept that primary cutaneous B-cell lymphomas are derived from acquired SALT - probably as a result of chronic antigenic stimulation- there is still debate about the origin of the neoplastic cells and consequently about the terminology2,3 of these lymphomas. As long as the origin of the B-cells in these lymphomas is unknown and as long as their is no consencus on the definition of the term marginal zone B-cell lymphomas, the EORTC group has decided to use the terms primary cutaneous follicle center cell lymphoma and immunocytoma since they refer to known and wel defined clinic pathologic entities1,4
References