Histologic Identification of Malignant
Lymphoma Cutis
EDWIN R. FISHER, M.D.,
E. J. PARK, M.D.,
AND HARRY L. WECHSLER,
M.D.
From the Departments of Pathology and Dermatology, Shadyside Hospital
and University of Pittsburgh, Pittsburgh, Pennsylvania
ABSTRACT
Fisher, Edwin R., Park, E. J., and Wechsler, Harry L.: Histologic identification
of malignant lymphoma cutis. Am J Clin Pathol 65: 149-158,1976. Sections of
47 skin biopsies diagnosed during 1960-1970 as suggestive of or diagnostic of
malignant lymphoma were retrospectively analyzed. Thirteen with
monomorphous cutaneous infiltrates of reticulum cells or poorly differentiated lymphocytes were encountered; all were from patients who had
extracutaneous manifestations of reticulum-cell sarcoma, poorly differentiated
lymphosarcoma, or leukemia at the time of biopsy or within a year after biopsy.
Diagnosis of well-differentiated lymphosarcoma or leukemia cutis is more
tenuous, since mature lymphocytic infiltrates were encountered in patients
with or without evidence of extracutaneous lymphoma. These are designated
"unclassified" lymphocytic infiltrates of skin, requiring careful clinical
exclusion of these types of malignant lymphoma. Other purported histopathologic discriminants of malignant lymphoma and pseudolymphoma, the
latter term utilized to designate banal disorders characterized by a polymorphous infiltrate with or without atypical reticulum cells, are of little value for
their distinction. These diagnostic criteria for malignant lymphoma cutis
should clarify much of the pathologic and clinical uncertainty attendant upon
the so-called "lymphoreticular" infiltrates of the skin. (Key words: Lymphoma
cutis; Lymphocytoma; Pseudolymphoma cutis.)
I T IS WELL RECOGNIZED that lymphoreticular infiltrates of the skin represent a
heterogeneous clinical and pathologic
group of disorders. The benign lesions
have been variably designated as cutaneous
lymphoid hyperplasia, cutaneous lymphoplasia, lymphocytoma cutis, lymphadenosis
benigna cutis, lymphocytic infiltrate of skin,
reactive lymphoid hyperplasia, SpieglerFendt sarcoid, insect-bite granuloma, and
Received February 19, 1975; accepted for publication May 6, 1975.
Address reprint requests to Dr. Fisher: Department
of Pathology, Shadyside Hospital, 5230 Centre Avenue, Pittsburgh, Pennsylvania 15232.
149
pseudolymphoma. Undoubtedly, some instances of discoid lupus erythematosus and
other less specific dermatoses have masqueraded under one or the other of the
above appelations. A few attempts to obtain
some nosologic order from this congeries
have been made. Mach and Wilgram 6
categorized these lesions histopathologically as lymphatic, g r a n u l o m a t o u s ,
reticulum-cell, giant follicular, a n d
plasma-cell types, whereas Caro and Helwig2 recognized only three, the lymphoreticular, granulomatous and follicular. Both groups of investigators failed to
find any relationship between these
150
FISHER, PARK AND WECHSLER
A.J.C.P.—Vol.
65
\
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:,:-
-
^
Fie. \A (upper). Lowpower a p p e a r a n c e of
monomorphous mature
lymphocytic infiltrate in
patient with lymphocytic
leukemia, showing acanthosis and focal infiltration
of the epidermis (box), features purportedly not observed with malignant
lymphoma cutis. This lesion would be designated
"unclassified" lymphocytic
infiltrate of the skin. x 4 0 .
B (lower). Higher magnification of focus of epidermal infiltration in A, disclosing m o n o m o r p h o u s ,
well-differentiated lymphocytes. X400.
'Atf**
pathologic variants and their clinical manifestations. On the other hand, Clark and
associates 3 were able to correlate four
histopathologic appearances with clinical
features.
T h e significance of this polemic is
minimized when it is appreciated that, at
least from a pathologic standpoint, the
major concern relating to these benign
infiltrates is their distinction from the
malignant lymphomas. Mach and Wilgram 6
contended that the presence of nuclear
fragments, so-called "polychrome bodies,"
within the cytoplasm of histiocytes or lying
free within the infiltrate, a n d its
polymorphous nature were sufficient to
Fie. 2 (upper). Monomorphous, welldifferentiated lymphocytic infiltrate of
skin characteristic of "unclassified" lymphocytic infiltrate of skin from a patient
who has not manifested evidence of
extracutaneous malignant lymphoma
for 8 years since this biopsy. Epidermal
atrophy and a slight grenz zone are
present, x 100.
FIG. 3 (lower). Polymorphous infiltrate
in subcutis separating skeletal muscle
fibers from a patient without evidence of
malignant lymphoma. Some of the reticulum cells appear moderately atypical,
and mitoses are present. Nevertheless,
these features, accompanied by other
cells such as mature lymphocytes and
plasma cells, militate against a diagnosis
of malignant lymphoma and warrant the
designation "pseudolymphoma." X400.
152
FISHER, PARK AND WECHSLER
warrant a diagnosis of benign lymphoplasia. Caro and Helwig, 2 after analyzing a
number of pathologic discriminants, concluded that there was no single criterion
that might allow for this differentiation,
although the presence of pseudoepitheliomatous hyperplasia, follicle formation
and/or a polymorphous infiltrate favored
a benign process. Even less certain in
this regard are the comments of Clark
and associates, 3 who indicated that it
was incommodious to diagnose malignant
lymphoma or leukemia on the basis of
histopathologic examination. This dilemma appears to be compounded by the
realization that some patients with extracutaneous evidence of malignant lymphoma have been purported to have
dermal lesions of both benign and malignant histopathologic appearances. 2
These considerations, as well as our own
somewhat enigmatic experience relating to
the histopathologic distinction of benign
and malignant lymphoreticular infiltrates
of the skin, have prompted us to analyze
our own material with the hope of obtaining some objective histopathologic criteria
useful for the distinction of benign and
malignant cutaneous lymphoreticular
infiltrates, or at least helpful in formulating
a diagnostic scheme for these lesions that
might possess practical clinicopathologic
value.
Materials and Methods
Sections of 47 biopsy specimens from
47 patients originally diagnosed as having
malignant lymphoma or features suggestive of same, exclusive of mycosis fungoides
or Hodgkin's disease, during the period
1966-1970, for whom follow-up information was available, were studied. All were
reviewed in regard to the following histopathologic characteristics without prior
knowledge of the clinical courses of the
patients: (1) epidermal alterations; (2)
qualitative and quantitative characteristics
A.J.C.P.—Vol.
65
of the infiltrate, including site in dermis,
pattern of distribution, predilection for
appendages, and purity; (3) vascular involvement; (4) grenz zone; (5) follicle formation; (6) polychrome bodies; (7) miscellaneous features. The findings were then
correlated with the. clinical courses of the
patients, including hematologic findings or
other evidence of extracutaneous malignant lymphoma, age, sex, clinical impression of the cutaneous lesion, and the time
of appearance of the latter in relation to
other evidence of malignant lymphoma.
Results
Thirteen of the 47 patients manifested
extracutaneous evidence of malignant
lymphoma by lymph nodal or organ involvement. In two of these cases
hematologic evidence of lymphocytic
leukemia was present. T h e extracutaneous
features of malignant lymphoma were
clinically evident in six of the 13 cases at the
time of the skin biopsy and subsequently
appeared within a year in the remaining
seven. No evidence of malignant lymphoma has become manifest four to eight
years after biopsy in the remaining 34.
There was no statistically significant
difference between average ages of patients
with malignant lymphoma cutis (57.5 years)
and those with pseudolymphoma (52.0
years) (p > .05). Both types of lesions
occurred with the same frequency in both
sexes. All patients in the study were white
except one in the pseudolymphoma group
who was black.
Fifty per cent of pseudolymphomas were
found on the extremities, whereas this site
was involved in only 16% of the cases of
malignant lymphoma. More than two
thirds of the lesions of the latter occurred
on the face or neck, but only 20% of the
pseudolymphomas were found at these
sites. All 13 instances of malignant lymphoma were correctly diagnosed clinically,
although 56% of the pseudolymphomas
February 1976
FIG. AA (upper). Low-power a,
ance of deep, diffuse monomor
infiltrate in skin of a patient
subsequently developed nodal mani
tations of reticulum-cell sarcoma. x<'
(lower). Higher magnification of the _.
reveals their reticulum-cell nature.
X400.
LYMPHOMA CUTIS
153
154
FISHER, PARK AND WECHSLER
A.J.C.P. —Vol. 65
FIG. 5.4 (upper). Focal monomorphous
infiltrate in dermis of a patient who at the
time of biopsy manifested extracutaneous evidence of prolymphocytic lymphosarcoma. X40.B (lower). High-power
appearance of the infiltrative cells. They
are slightly smaller than the reticulum
cells depicted in Figure 4B, but larger
than well-differentiated lymphocytes.
X400.
*J&'&tt&&2)t&£.
were regarded clinically as malignant lymphoma.
Epidermal alterations, including infiltration by lymphoid elements, acanthosis,
and/or atrophy, were encountered with
approximately the same frequency in both
groups (Fig. L4 and .6). A similar situation
obtained regarding the presence of a
February 1976
LYMPHOMA CUTIS
155
Fie. 6. Diffuse infiltrate of mature
lymphocytes among skeletal muscle
fibers of subcutis from a patient without
evidence of malignant lymphoma for 8
years after biopsy. T h e lesion is
designated "unclassified" lymphocytic
infiltrate of skin. X40.
so-called grenz zone (Fig. 2). The quantity cells (Fig. 4A and B) or prolymphocytes
of infiltrate and its depth of penetration and/or lymphoblasts (Fig. 5A and .6) were
through the dermis were found to be encountered only in the malignant lymrelatively inconsistent discriminants, al- phoma group. Thus, there were six examthough a higher frequency of involvement ples of reticulum-cell sarcoma and two
of the deep dermis and subcutis occurred in poorly differentiated lymphosarcomas
the malignant lymphoma group (60 vs. (prolymphocytic or lymphoblastic). Pure
20%). The infiltrate was assessed as being infiltrates of mature lymphocytes were
heavy in two thirds of the malignant found in five patients of the malignant
lymphomas and a third of the pseudolym- l y m p h o m a g r o u p and 17 of the
phomas. T h e infiltrate was regarded pseudolymphoma patients. They were
equally as diffuse or focal in examples of either diffuse (Figs. 2 and 6) or focal in the
malignant lymphoma, whereas it was focal latter (Fig. 1A and B). They were focal in
in two thirds of the pseudolymphomas.
two patients with chronic lymphocytic
Although in four cases the lesions were leukemia. The infiltrates were diffuse in the
regarded originally as suggestive of malig- remaining three with extracutaneous mannant lymphoma because of the presence of ifestations of lymphocytic or well-differatypical reticulum-cell elements, none entiated lymphosarcoma.
showed extracutaneous involvement (Fig.
Vascular involvement characterized by
3). This review of these sections disclosed mural infiltration and predilection of the
the presence of equal or greater numbers of infiltrate for skin appendages was found
mature lymphocytes, banal macrophages, with the same frequency in both groups.
and some plasma cells, attesting to their Polychrome bodies were found in only 10%
polymorphous nature, which warrants of the pseudolymphomas. None were
their designation as pseudolymphoma.
found in the examples of malignant lymMonomorphous infiltrates of reticulum phoma.
FISHER, PARK AND WECHSLER
156
Discussion
No information concerning the etiology
or pathogenesis of the benign pseudolymphomatous cutaneous lesion has been
revealed in this study. The selection of only
cases initially diagnosed pathologically as
malignant lymphoma would appear to
militate against information in this regard
and has limited the number of cases of such
lesions available for study. Nevertheless,
despite the relatively small number of cases,
this type of retrospective study has provided meaningful, objective criteria for the
histopathologic identification of malignant
lymphoma cutis. Utilization of a four-year
disease-free period as evidence of a benign
clinical process coincides with the experience of others. 2 It has been substantiated by
the finding in this study that manifestations
of extracutaneous malignant lymphoma, if
not present at the time of biopsy, became
evident within a year following it.
Caro and Helwig 2 have emphasized that a
constellation of histopathologic features
allows for the distinction of pseudolymphoma and malignant lymphoma cutis. A
monomorphous infiltrate favored a diagnosis of malignant lymphoma, whereas
epidermal acanthosis and lymph follicles
were more characteristic of the benign
process. Lymph follicle formation and
polychrome bodies have been purported by
Mach and Wilgram 6 to be characteristic of
pseudolymphoma (cutaneous lymphoid
hyperplasia). Interestingly, they indicated
that distinction of the latter from malignant
lymphoma was not difficult, although it
should be noted that their study did not
include any series of the latter. Our own
findings indicate that a monomorphous
infiltrate of either immature lymphocytic
elements (prolymphocytes or lymphoblasts) or reticulum cells, regardless of
other alterations, appears sufficient to
warrant diagnosis of poorly differentiated
lymphosarcoma or reticulum-cell sarcoma
cutis, respectively. Objective diagnosis of
A.J.C.P.—Vol.
65
mature lymphocytic lymphosarcoma or
leukemia, on the other hand, as emphasized by Clark and associates, 3 is more
tenuous, if not impossible, on the basis
of histopathologic examination alone.
Further, the presence of some atypical cells
in an otherwise diffuse polymorphous
infiltrate does not signify malignancy.
Their presence has been observed in a
variety of banal dermatoses, including
pityriasis lichenoides of Mucha Haberm a n n 7 a n d the cases described by
Macaulay 5 and Bernstein and associates. 1
These findings also minimize the significance of such conventionally held diagnostic criteria for pseudolymphoma as
epidermal alteration and absence of grenz
zone. 4 Although polychrome bodies were
not encountered in the malignant lymphomas, their relative infrequency in those
lesions of patients with benign clinical
courses also minimizes their significance as
a discriminant of the malignant and benign
disorders. Since follicle formation precludes a diagnosis of malignant lymphoma
in our laboratory, as expected, none of the
cases showed such change. However, their
presence still remains a valuable feature of
benignity. Unfortunately, such configurations are not too frequent.
It is of interest that no significant
difference in the sex predilection or age of
patients with malignant lymphoma and
pseudolymphoma could be found. Also,
more malignant lesions were observed on
the face than on the extremities. These
clinical features are divergent from those
recorded by Caro and Helwig, 2 who reported a greater male incidence, older age,
and propensity of malignant lesions for the
body, scalp and extremities compared with
those that were regarded as benign. This
dichotomy may reflect the difference in
selection of cases in the two studies, as well
as the source of their material from a
p r e d o m i n a t e l y male p o p u l a t i o n . It
nevertheless indicates the inconsistency
February 1976
157
LYMPHOMA CUTIS
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FIG. 7A (upper). Focal, monomorphous, well-differentiated lymphocytic
infiltrate in dermis of a patient without
evidence of malignant lymphoma. This
was a relatively common appearance of
the lesion designated "unclassified" lymphocytic infiltrate of skin X100. B
(lower). High-power appearance of the
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FISHER, PARK AND WECHSLER
A.J.C.P.—Vol.
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Acknowledgments: Some of the case material utilized
and unreliability of clinical features for the
in this study was generously provided by Drs. R.
diagnosis of malignant lymphoma cutis Goldblum, M. Mitchell, F. Hegarty, F. Krugh, and E.
except in those individuals with existing Farney, of Pittsburgh.
extracutaneous involvement.
References
From a practical standpoint, the above
considerations indicate the propriety of
1. Bernstein H, Supack J, Ackerman B: Cutaneous
pseudolymphoma resulting from antigen injecrendering histopathologic diagnoses of
tions. Arch Dermatol 110:756-757, 1974
either reticulum-cell sarcoma or poorly
2. Caro WA, Helwig EB: Cutaneous lymphoid
hyperplasia. Cancer 24:487-502, 1969
differentiated lymphosarcoma. It is now
3. Clark WH, Mihm MC, Reed RJ, et al: The
our practice to designate all monomorlymphocytic infiltrates of skin. Hum Pathol
phous mature lymphocytic infiltrates sim5:25-43, 1974
4. Lever WF: Histopathology of the Skin. Fourth
ply "unclassified" lymphocytic infiltrates of
edition. Philadelphia, J. B. Lippincott, 1967, pp
skin. This nomenclature prompts the clini736-767
5. Macaulay WL: Lymphomatoid papulosis. A concian to investigate further the possibility of
tinuing self-healing eruption, clinically
malignant lymphoma in patients with such
benign-histologically malignant. Arch Dermatol 97:23-30, 1968
lesions. On the other hand, all polymorph6. Mach KW, Wilgram GF: Characteristic hisous infiltrates of skin, with or without
topathology of cutaneous lymphoplasia (lymfollicle formation or a modicum of atypical
phocytoma). Arch Dermatol 94:26-32, 1966
7. Verallo VM, Haserick JR: Mucha-Habermann's
cells, are considered instances of
disease simulating lymphoma cutis. Arch Derpseudolymphoma.
matol 94:295-299, 1966
I