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April 2003
Sentinel lymph node biopsy for problematic spitzoid melanocytic lesions
Spindle or epithelioid melanocytic proliferations, or both, that
display overlapping histopathologic features of Spitz nevus and
Spitz-like melanoma are diagnostically difficult and controversial
melanocytic tumors. There are reports of such lesions metastasizing
to regional lymph nodes, with a few widely disseminating, resulting
in death. The authors reviewed clinical and histopathologic data
on patients who were identified at the University of Michigan with
atypical or borderline spitzoid melanocytic proliferations and who
underwent sentinel lymph node (SLN) biopsy. Six male and 12 female
patients, ages five to 32 years (mean, 16 years), had tumors ranging
in thickness from 1.2 mm to 7.9 mm (mean, 3.5 mm). Atypical histologic
features that were present most frequently included incomplete maturation
(100 percent), deep dermal mitoses (89 percent), nuclear pleomorphism
(56 percent), and focal sheet-like growth (56 percent). Eight of
18 patients (44 percent) had SLN metastasis and were offered adjuvant
treatment. One of eight patients (13 percent) with SLN-positive
results who underwent regional lymphadenectomy had one additional
involved lymph node. All 18 patients were alive and well with no
evidence of recurrent or metastatic disease after a followup of
three to 42 months (mean, 12 months). The authors concluded that
histologically atypical or borderline spitzoid, melanocytic tumors
are diagnostically challenging and controversial melanocytic lesions,
some of which represent unrecognized melanomas. SLN biopsy aids
in confirming a diagnosis of melanoma and identifies patients who
may benefit from early therapeutic lymph node dissection or adjuvant
therapy, or both.
Su LD, Fullen DR, Sondak VK, et al. Sentinel lymph
node biopsy for patients with problematic spitzoid melanocytic lesions.
A report on 18 patients. Cancer. 2003;97: 499–507.
Reprints: Dr. Lyndon D. Su, Dept. of Pathology, Division of Dermatopathology,
University of Michigan Medical Center, Medical Sciences I, M5224,
1301 Catherine St., Ann Arbor, MI 48109-0602;
[email protected]
Expression
of cytokeratins 17 and 5/6 in aggressive
breast carcinomas
Markers that offer prognostic information independent of other variables
may help in guiding therapy and are particularly important in early
stage carcinomas. In a study of 505 breast carcinomas (median followup,
63 months) analyzed by tissue microarray, expression of cytokeratin
17 or 5/6, or both, was a significant prognostic factor independent
of tumor size, tumor grade, Her2/neu status, estrogen-receptor expression,
and GATA-3 status in node-negative carcinomas. Further, no significant
correlation was identified between the expression of these basal
cytokeratins and Her2/neu expression. Ninety of the 564 tumors (16
percent) reacted with cytokeratin 17 or 5/6, or both. (Survival
data were available for 505 cases.) In 245 patients with negative
lymph nodes, the survival rate was lower for patients with tumors
expressing these basal cytokeratins (P=0.006). Identification of
this subset of aggressive breast carcinoma may help in making treatment
decisions and designing therapies with a specific target.
Van de Rijn M, Perou CM, Tibshirani R, et al.
Expression of cytokeratins 17 and 5 identifies a group of breast
carcinomas with poor clinical outcome. Am J Pathol. 2002;161:1991–1996.
Reprints: Dr. Matt van de Rijn, L235 Dept. of Pathology, Stanford
University Medical Center, 300 Pasteur Drive, Stanford, CA 94305;
[email protected]
Diagnostic
value of HMB-45 and anti-Melan A staining of
sentinel lymph nodes
Numerous immunohistochemical stains have been used to detect metastatic
melanoma in sentinel lymph node biopsies. HMB-45 is considered by
some to be a specific tool to detect early metastatic melanoma.
One or two isolated HMB-45-positive cells occasionally may cause
complications in diagnostic interpretation. The authors conducted
a study to evaluate the reliability of HMB-45 staining of SLNs with
sparse isolated positive cells and to compare it with anti-Melan
A antibody. HMB-45 and anti-Melan A antibody immunostaining were
performed on 15 histologically negative SLNs excised from patients
with malignant melanoma (group A) and 15 histologically negative
SLNs excised from patients with breast carcinoma (group B). None
of the patients had clinical evidence of systemic metastasis at
the time of SLN biopsy. Five cutaneous biopsies with changes of
postinflammatory hyperpigmentation (PIHP) were also stained with
both antibodies. HMB-45 staining was repeated in all group B SLNs
after blocking endogenous biotins. Electron microscopic studies
were performed on all cases of PIHP. Isolated HMB-45-stained cells
were present in six of 15 SLNs removed for malignant melanoma; eight
of 15 for breast carcinoma; and three of five cutaneous biopsies
of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins
in six of eight positive SLNs from group B. Anti-Melan A antibody
was negative in all SLNs from group A and B and in dermal melanophages
of all five cases of PIHP. HMB-45 positivity was demonstrated in
histologically negative SLNs and cutaneous biopsies, especially
in the milieu of aggregated melanophages. Phagocytosis of premelanosomes
by macrophages in the draining lymph nodes may account for isolated
cell positivity and can hinder correct diagnostic interpretation.
HMB-45 may not be a reliable marker for detecting micrometastasis
of malignant melanoma and requires correlation with other immunohistochemical
markers, such as anti-Melan A antibody, to enhance specificity.
Mahmood MN, Lee MW, Linden MD, et al. Diagnostic
value of HMB-45 and anti-Melan A staining of sentinel lymph nodes
with isolated positive cells. Mod Pathol. 2002; 15(12):
1228–1293.
Reprints: Dr. Muhammad N. Mahmood, Dept. of Pathology, Henry Ford
Hospital, K-6, Clinic Building, 2799 W. Grand Blvd., Detroit, MI
48202; [email protected]
Pathologic
prion protein in the olfactory epithelium
in sporadic CJD
It has been difficult to establish a definitive diagnosis of Creutzfeldt-Jakob
disease without a brain biopsy. The olfactory cortexes and the olfactory
tracts, however, are involved in sporadic Creutzfeldt-Jakob disease.
The authors examined peripheral regions of the olfactory sensory
pathway, including the olfactory mucosa, to assess whether pathologic
infectious prion protein (PrPsc) is deposited in the epithelium
lining the nasal cavity. They studied nine patients with neuropathologically
confirmed sporadic Creutzfeldt-Jakob disease from whom they obtained
the brain, cribriform plate with the attached olfactory mucosa,
and surrounding respiratory epithelium at autopsy. Control samples
of nasal mucosa were obtained post mortem or at biopsy from age-matched
control subjects and from control patients with other neurodegenerative
diseases. The olfactory and respiratory mucosa and the intracranial
olfactory system were analyzed by light microscopy, immunohistochemistry,
and Western blotting for pathological changes and for deposition
of PrPsc. In all nine patients with sporadic Creutzfeldt-Jakob disease,
PrPsc was found in the olfactory cilia and central olfactory pathway
but not in the respiratory mucosa. No PrPsc was detected in any
of the tissue samples from the 11 controls. The authors’ pathological
and biochemical studies showed that PrPsc is deposited in the neuroepithelium
of the olfactory mucosa in patients with sporadic Creutzfeldt-Jakob
disease, indicating that olfactory biopsy may provide diagnostic
information in living patients. The olfactory pathway may represent
a route of infection and a means of spreading prions.
Zanusso G,
Ferrari S, Cardone F, et al. Detection of pathologic prion protein
in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease.
N Engl J Med. 2003; 348: 711–719.
Reprints: Dr. S. Monaco, Section of Clinical Neurology, Dept. of
Neurologic and Visual Sciences, Policlinico G.B. Rossi, Piazzale
L.A. Scuro 10, 37134 Verona, Italy; salvatore. monaco@
mail.univr.it
Whipple resections in patients without malignancy
Whipple resections (pancreaticoduodenectomy)
has evolved into a safe procedure to treat pancreatic adenocarcinoma
and refractory chronic pancreatitis in major high-volume medical
centers. Some Whipple resections performed for a clinical suspicion
of malignancy, however, reveal only benign disease on pathologic
examination. The authors evaluated the frequency of such Whipple
resections without tumor in a large series of pancreaticoduodenectomies
and classified the diverse pancreatic and biliary tract diseases
present in these specimens. Of 442 Whipple resections performed
from 1999 through 2001, 47 (10.6 percent) were negative for neoplastic
disease and, in 40 cases, had been performed for a clinical suspicion
of malignancy. Most Whipple resections revealed benign pancreatic
disease, including eight (17 percent) cases of alcohol-associated
chronic pancreatitis, four (8.5 percent) of gallstone-associated
pancreatitis, one (2.1 percent) of pancreas divisum, six (12.8 percent)
of “ordinary” chronic pancreatitis of unknown etiology,
and 11 (23.4 percent) of lymphoplasmacytic sclerosing pancreatitis.
Patients with lymphoplasmacytic sclerosing pancreatitis, in particular,
were thought to harbor malignancy, whereas only 13 of 19 (68.4 percent)
Whipple resections showing histologically ordinary forms of chronic
pancreatitis were performed for a clinical suspicion of malignancy.
Benign biliary tract disease, including three cases of primary sclerosing
cholangitis, two cases of choledocholithiasis-associated chronic
biliary tract disease, and four fibroinflammatory strictures isolated
to the intrapancreatic common bile duct, was a common etiology for
clinically suspicious Whipple resections (22.5 percent of cases).
Pancreatic intraepithelial neoplasia (PanIN) was a common finding
among all pancreata, whether involved by pancreatitis or histologically
normal. Overall, PanIN 1A/1B was present in 68.1 percent, PanIN
2 in 40.4 percent, and PanIN 3 in 2.1 percent. These findings indicate
that benign but clinically suspicious Whipple resections are relatively
common in high-volume medical centers (9.2 percent) and reveal a
diverse group of clinicopathologically distinctive pancreatic and
biliary tract diseases.
Abraham SC, Wilentz RE, Yeo CJ, et al. Pancreaticoduodenectomy
(Whipple resections) in patients without malignancy. Are they all
‘chronic pancreatitis’? Am J Surg Pathol. 2003;27(1):110–120.
Reprints: Dr. Susan C. Abraham, Dept. of Pathology, Hilton 11, Mayo
Clinic, 220 First St., SW, Rochester, MN 55905; abraham. susan@
mayo.edun
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